AHA Scientific Sessions 2018

CHICAGO – A European clinical trial that targeted a mean arterial blood pressure after cardiac arrest higher than what the existing guidelines recommend found that the approach was safe, improved blood flow and oxygen to the brain, helped patients recover quicker, and reduced the number of adverse cardiac events, although it did not reduce the extent of anoxic brain damage or improve functional outcomes, the lead investigator reported at the American Heart Association scientific sessions.

The Neuroprotect trial randomly assigned 112 adult survivors of an out-of-hospital cardiac arrest who were unconscious upon admission to two study groups: early goal-directed hemodynamic optimization (EGDHO), in which researchers used a targeted mean arterial pressure (MAP) of 85-100 mm Hg and mixed venous oxygen saturation between 65% and 75% during the first 36 hours after ICU admission; and the standard care group, in which they used the guideline-recommended MAP target of 65 mm Hg, said Koen Ameloot, MD, of East Limburg Hospital in Genk, Belgium.

“EGDHO clearly improved cerebral perfusion and oxygenation, thereby for the first time providing the proof of concept for this new hemodynamic target,” Dr. Ameloot said. “However, this did not result in the reduction of the extent of anoxic brain hemorrhage or effusion rate on MRI or an improvement in functional outcome at 180 days.”

He noted the trial was predicated on improving upon the so-called “two-hit” model of cardiac arrest sequelae: the first hit being the no-flow and low-flow period before achieving restoration of spontaneous circulation; the second hit being hypoperfusion and reperfusion injury during ICU stay.

Dr. Ameloot referenced a study in which he and other coauthors reported that patients with a MAP target of 65 mm Hg “experience a profound drop of cerebral oxygen saturation during the first 12 hours of ICU stay that may cause additional brain damage” (Resuscitation. 2018;123:92-7).

The researchers explored the question of what is the optimal MAP if a target of 65 mm Hg is too low, Dr. Ameloot said. “We showed that maximal brain oxygenation is achieved with a MAP of 100 mm Hg, while lower MAPs were associated with submaximal brain perfusion and higher MAPs with excessive after-load, a reduction in stroke volume, and suboptimal cerebral oxygenation.”

During the 36-hour intervention period, the EGDHO patients received higher doses of norepinephrine, Dr. Ameloot said. “This resulted in significant improvement of cerebral oxygenation during the first 12 hours and was paralleled by significantly higher cerebral perfusion in the subset of patients in whom Doppler measurements were performed,” he said. “While patients allocated to the MAP 65 mm Hg target experienced a profound drop of cerebral oxygenation during the critical first 6-12 hours of ICU stay, cerebral oxygenation was maintained at 67% in patients assigned to EGDHO.”

However, the rate of anoxic brain damage, measured as the percentage of irreversibly damaged anoxic voxels on diffusion-weighted MRI – the primary endpoint of the study – was actually higher in the EGDHO group, 16% vs. 12%, Dr. Ameloot said. “The percentage of anoxic voxels was only a poor predictor of favorable neurological outcome at 180 days, questioning the validity of the primary endpoint,” he said. He also noted that 23% of the trial participants did not have an MRI scan because of higher than expected 5-day rates of death.

“The percentage of patients with favorable neurological outcome tended to be somewhat higher in the intervention arm, although this did not reach statistical significance at ICU discharge and at 180 days,” Dr. Ameloot said. He noted that 42% of the intervention group and 33% of controls in the full-analysis set (P = .30) and 43% and 27%, respectively, in the per-protocol set (P = .15) had a favorable neurological outcome, as calculated using the Glasgow-Pittsburgh Cerebral Performance Category scores of 1 or 2, at 180 days.

The study did not reveal any noteworthy differences in ICU stay (7 vs. 8 days, P = .13) or days on mechanical ventilation (5 vs. 7, P = .31), although fewer patients in the EGDHO group required a tracheostomy (4% vs. 18%, P = .02). The intervention group also had lower rates of cardiac events, including recurrent cardiac arrest, limb ischemia, new atrial fibrillation, and pulmonary edema (13% vs. 33%; P = .02), Dr. Ameloot said.

Future post-hoc analyses of the data will explore the hypothesis that higher blood pressure leads to improved coronary perfusion and reduced infarct size, thus improving prognosis, he added.

“Should this trial therefore be the definite end to the promising hypothesis that improving brain oxygenation might reduce the second hit in post–cardiac arrest patients? I don’t think so,” Dr. Ameloot said. He noted a few limits to the study: that the perfusion rate on MRI was a poor predictor of 180-day outcome; that more patients than expected entered the trial without receiving basic life support and with nonshockable rhythms; and that there was possibly less extensive brain damage among controls at baseline. “Only an adequately powered clinical trial can provide an answer about the effects of EGDHO in post–cardiac arrest patients,” Dr. Ameloot said.

Dr. Ameloot had no financial relationships to disclose.

SOURCE: Ameloot K et al. AHA 2018, Abstract 18620
 

CHICAGO – A European clinical trial that targeted a mean arterial blood pressure after cardiac arrest higher than what the existing guidelines recommend found that the approach was safe, improved blood flow and oxygen to the brain, helped patients recover quicker, and reduced the number of adverse cardiac events, although it did not reduce the extent of anoxic brain damage or improve functional outcomes, the lead investigator reported at the American Heart Association scientific sessions.

The Neuroprotect trial randomly assigned 112 adult survivors of an out-of-hospital cardiac arrest who were unconscious upon admission to two study groups: early goal-directed hemodynamic optimization (EGDHO), in which researchers used a targeted mean arterial pressure (MAP) of 85-100 mm Hg and mixed venous oxygen saturation between 65% and 75% during the first 36 hours after ICU admission; and the standard care group, in which they used the guideline-recommended MAP target of 65 mm Hg, said Koen Ameloot, MD, of East Limburg Hospital in Genk, Belgium.

“EGDHO clearly improved cerebral perfusion and oxygenation, thereby for the first time providing the proof of concept for this new hemodynamic target,” Dr. Ameloot said. “However, this did not result in the reduction of the extent of anoxic brain hemorrhage or effusion rate on MRI or an improvement in functional outcome at 180 days.”

He noted the trial was predicated on improving upon the so-called “two-hit” model of cardiac arrest sequelae: the first hit being the no-flow and low-flow period before achieving restoration of spontaneous circulation; the second hit being hypoperfusion and reperfusion injury during ICU stay.

Dr. Ameloot referenced a study in which he and other coauthors reported that patients with a MAP target of 65 mm Hg “experience a profound drop of cerebral oxygen saturation during the first 12 hours of ICU stay that may cause additional brain damage” (Resuscitation. 2018;123:92-7).

The researchers explored the question of what is the optimal MAP if a target of 65 mm Hg is too low, Dr. Ameloot said. “We showed that maximal brain oxygenation is achieved with a MAP of 100 mm Hg, while lower MAPs were associated with submaximal brain perfusion and higher MAPs with excessive after-load, a reduction in stroke volume, and suboptimal cerebral oxygenation.”

During the 36-hour intervention period, the EGDHO patients received higher doses of norepinephrine, Dr. Ameloot said. “This resulted in significant improvement of cerebral oxygenation during the first 12 hours and was paralleled by significantly higher cerebral perfusion in the subset of patients in whom Doppler measurements were performed,” he said. “While patients allocated to the MAP 65 mm Hg target experienced a profound drop of cerebral oxygenation during the critical first 6-12 hours of ICU stay, cerebral oxygenation was maintained at 67% in patients assigned to EGDHO.”

However, the rate of anoxic brain damage, measured as the percentage of irreversibly damaged anoxic voxels on diffusion-weighted MRI – the primary endpoint of the study – was actually higher in the EGDHO group, 16% vs. 12%, Dr. Ameloot said. “The percentage of anoxic voxels was only a poor predictor of favorable neurological outcome at 180 days, questioning the validity of the primary endpoint,” he said. He also noted that 23% of the trial participants did not have an MRI scan because of higher than expected 5-day rates of death.

“The percentage of patients with favorable neurological outcome tended to be somewhat higher in the intervention arm, although this did not reach statistical significance at ICU discharge and at 180 days,” Dr. Ameloot said. He noted that 42% of the intervention group and 33% of controls in the full-analysis set (P = .30) and 43% and 27%, respectively, in the per-protocol set (P = .15) had a favorable neurological outcome, as calculated using the Glasgow-Pittsburgh Cerebral Performance Category scores of 1 or 2, at 180 days.

The study did not reveal any noteworthy differences in ICU stay (7 vs. 8 days, P = .13) or days on mechanical ventilation (5 vs. 7, P = .31), although fewer patients in the EGDHO group required a tracheostomy (4% vs. 18%, P = .02). The intervention group also had lower rates of cardiac events, including recurrent cardiac arrest, limb ischemia, new atrial fibrillation, and pulmonary edema (13% vs. 33%; P = .02), Dr. Ameloot said.

Future post-hoc analyses of the data will explore the hypothesis that higher blood pressure leads to improved coronary perfusion and reduced infarct size, thus improving prognosis, he added.

“Should this trial therefore be the definite end to the promising hypothesis that improving brain oxygenation might reduce the second hit in post–cardiac arrest patients? I don’t think so,” Dr. Ameloot said. He noted a few limits to the study: that the perfusion rate on MRI was a poor predictor of 180-day outcome; that more patients than expected entered the trial without receiving basic life support and with nonshockable rhythms; and that there was possibly less extensive brain damage among controls at baseline. “Only an adequately powered clinical trial can provide an answer about the effects of EGDHO in post–cardiac arrest patients,” Dr. Ameloot said.

Dr. Ameloot had no financial relationships to disclose.

SOURCE: Ameloot K et al. AHA 2018, Abstract 18620
 

CHICAGO – A European clinical trial that targeted a mean arterial blood pressure after cardiac arrest higher than what the existing guidelines recommend found that the approach was safe, improved blood flow and oxygen to the brain, helped patients recover quicker, and reduced the number of adverse cardiac events, although it did not reduce the extent of anoxic brain damage or improve functional outcomes, the lead investigator reported at the American Heart Association scientific sessions.

The Neuroprotect trial randomly assigned 112 adult survivors of an out-of-hospital cardiac arrest who were unconscious upon admission to two study groups: early goal-directed hemodynamic optimization (EGDHO), in which researchers used a targeted mean arterial pressure (MAP) of 85-100 mm Hg and mixed venous oxygen saturation between 65% and 75% during the first 36 hours after ICU admission; and the standard care group, in which they used the guideline-recommended MAP target of 65 mm Hg, said Koen Ameloot, MD, of East Limburg Hospital in Genk, Belgium.

“EGDHO clearly improved cerebral perfusion and oxygenation, thereby for the first time providing the proof of concept for this new hemodynamic target,” Dr. Ameloot said. “However, this did not result in the reduction of the extent of anoxic brain hemorrhage or effusion rate on MRI or an improvement in functional outcome at 180 days.”

He noted the trial was predicated on improving upon the so-called “two-hit” model of cardiac arrest sequelae: the first hit being the no-flow and low-flow period before achieving restoration of spontaneous circulation; the second hit being hypoperfusion and reperfusion injury during ICU stay.

Dr. Ameloot referenced a study in which he and other coauthors reported that patients with a MAP target of 65 mm Hg “experience a profound drop of cerebral oxygen saturation during the first 12 hours of ICU stay that may cause additional brain damage” (Resuscitation. 2018;123:92-7).

The researchers explored the question of what is the optimal MAP if a target of 65 mm Hg is too low, Dr. Ameloot said. “We showed that maximal brain oxygenation is achieved with a MAP of 100 mm Hg, while lower MAPs were associated with submaximal brain perfusion and higher MAPs with excessive after-load, a reduction in stroke volume, and suboptimal cerebral oxygenation.”

During the 36-hour intervention period, the EGDHO patients received higher doses of norepinephrine, Dr. Ameloot said. “This resulted in significant improvement of cerebral oxygenation during the first 12 hours and was paralleled by significantly higher cerebral perfusion in the subset of patients in whom Doppler measurements were performed,” he said. “While patients allocated to the MAP 65 mm Hg target experienced a profound drop of cerebral oxygenation during the critical first 6-12 hours of ICU stay, cerebral oxygenation was maintained at 67% in patients assigned to EGDHO.”

However, the rate of anoxic brain damage, measured as the percentage of irreversibly damaged anoxic voxels on diffusion-weighted MRI – the primary endpoint of the study – was actually higher in the EGDHO group, 16% vs. 12%, Dr. Ameloot said. “The percentage of anoxic voxels was only a poor predictor of favorable neurological outcome at 180 days, questioning the validity of the primary endpoint,” he said. He also noted that 23% of the trial participants did not have an MRI scan because of higher than expected 5-day rates of death.

“The percentage of patients with favorable neurological outcome tended to be somewhat higher in the intervention arm, although this did not reach statistical significance at ICU discharge and at 180 days,” Dr. Ameloot said. He noted that 42% of the intervention group and 33% of controls in the full-analysis set (P = .30) and 43% and 27%, respectively, in the per-protocol set (P = .15) had a favorable neurological outcome, as calculated using the Glasgow-Pittsburgh Cerebral Performance Category scores of 1 or 2, at 180 days.

The study did not reveal any noteworthy differences in ICU stay (7 vs. 8 days, P = .13) or days on mechanical ventilation (5 vs. 7, P = .31), although fewer patients in the EGDHO group required a tracheostomy (4% vs. 18%, P = .02). The intervention group also had lower rates of cardiac events, including recurrent cardiac arrest, limb ischemia, new atrial fibrillation, and pulmonary edema (13% vs. 33%; P = .02), Dr. Ameloot said.

Future post-hoc analyses of the data will explore the hypothesis that higher blood pressure leads to improved coronary perfusion and reduced infarct size, thus improving prognosis, he added.

“Should this trial therefore be the definite end to the promising hypothesis that improving brain oxygenation might reduce the second hit in post–cardiac arrest patients? I don’t think so,” Dr. Ameloot said. He noted a few limits to the study: that the perfusion rate on MRI was a poor predictor of 180-day outcome; that more patients than expected entered the trial without receiving basic life support and with nonshockable rhythms; and that there was possibly less extensive brain damage among controls at baseline. “Only an adequately powered clinical trial can provide an answer about the effects of EGDHO in post–cardiac arrest patients,” Dr. Ameloot said.

Dr. Ameloot had no financial relationships to disclose.

SOURCE: Ameloot K et al. AHA 2018, Abstract 18620
 

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

CHICAGO – High-risk hospitalized patients with atrial fibrillation (AF) whose doctors monitored them with a computerized alert system were more than twice as likely to be on anticoagulation and had significantly lower rates of death and other cardiovascular events, compared with patients on a standard admissions protocol, according to results of a randomized, controlled trial presented at the American Heart Association Scientific Sessions.

“Alert-based computerized decision support [CDS] increased the prescription of anticoagulation for stroke prevention in atrial fibrillation during hospitalization, at discharge, and at 90 days after randomization in high-risk patients,” said Gregory Piazza, MD, of Brigham and Women’s Hospital, Boston, in presenting results of the AF-ALERT trial. “The reductions in major cardiovascular events was attributable to reductions in MI and stroke/transient ischemic attack at 90 days in patients whose physicians received the alert.”

The trial evaluated 458 patients hospitalized for AF or flutter and with CHA2DS2-VASc scores of 1-8 randomly assigned to the alert (n = 258) or no-alert (n = 210) groups.

Dr. Piazza explained that for those in the alert group, the CDS system notified physicians when the patient’s CHA₂DS₂-VASc score increased. From there, the physician could choose to open an order template to prescribe evidence-based medications to prevent stroke, to elect to review evidence-based clinical practice guidelines, or to continue with the admissions order with an acknowledged reason for omitting anticoagulation (such as high bleeding risk, low stroke risk, high risk for falls, or patient refusal of anticoagulation).

“In patients for whom their providers were alerted, 35% elected to open the stroke-prevention order set, a very tiny percentage elected to read the AF guidelines, and about 64% exited but provided a rationale for omitting anticoagulation,” Dr. Piazza noted.

The alert group was far more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%; P less than .0001), at discharge (23.8% vs. 12.9%; P = .003), and at 90 days (27.7% vs. 17.1%; P = .007) than the control group. The alert resulted in a 55% relative risk reduction in a composite outcome of death, MI, cerebrovascular event, and systemic embolic event at 90 days (11.3% vs. 21.9%; P = .002). The alert group had an 87% lower incidence of MI at 90 days (1.2% vs. 8.6%, P = .0002) and 88% lower incidence of cerebrovascular events or systemic embolism at 90 days (0% vs. 2.4%; P = .02). Death at 90 days occurred in 10.1% in the alert group and 14.8% in the control group (P = .13).

One of the limitations of the study, Dr. Piazza noted, was that the most dramatic finding – reduction of major cardiovascular events – was a secondary, not a primary, endpoint. “CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with atrial fibrillation.”

Moderator Mintu Turakhia, MD, of Stanford (Calif.) University, questioned the low rate of anticoagulation in the study’s control arm – 9.5% – much lower than medians reported in many registries. He also asked Dr. Piazza to describe the mechanism of action for prescribing anticoagulation in these patients.

Dr. Piazza noted the study population was hospitalized patients whose providers had decided prior to their admissions not to prescribe anticoagulation; hence, the rate of anticoagulation in these patients was actually higher than expected.

Regarding the mechanism of action, “the electronic alert seems to preferentially increase the prescription of [direct oral anticoagulants] over warfarin, and that may have been one of the mechanisms,” Dr. Piazza said. Another explanation he offered were “off-target” effects whereby, if providers have a better idea of a patient’s risk for a stroke or MI, they’ll be more aggressive about managing other risk factors.

“There are a number of interventions that could be triggered if the alert prompted the provider to have a conversation with patients about their risk of stroke from AF,” he said. “This may have impact beyond what we can tell from this simple [Best Practice Advisory in the Epic EHR system]. I think we don’t have a great understanding of the full mechanisms of CDS.”

Dr. Piazza reported financial relationships with BTG, Janssen, Bristol-Myers Squibb, Daiichi Sankyo, Portola, and Bayer. Daiichi Sankyo funded the trial. Dr. Turakhia reported relationships with Apple, Janssen, AstraZeneca, VA, Boehringer Ingelheim, Cardiva Medical, Medtronic, Abbott, Precision Health Economics, iBeat, iRhythm, MyoKardia, Biotronik, and an ownership Interest in AliveCor.

CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.

MItchel L. Zoler/MDedge News

Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.

Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).

The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.

Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).

The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.

Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.

FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.

mzoler@mdedge.com

SOURCE: Fuster V et al. AHA 2018, Abstract 18609.

CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.

MItchel L. Zoler/MDedge News

Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.

Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).

The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.

Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).

The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.

Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.

FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.

mzoler@mdedge.com

SOURCE: Fuster V et al. AHA 2018, Abstract 18609.

CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.

MItchel L. Zoler/MDedge News

Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.

Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).

The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.

Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).

The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.

Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.

FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.

mzoler@mdedge.com

SOURCE: Fuster V et al. AHA 2018, Abstract 18609.

CHICAGO – A novel smartphone app performed nearly as well as a standard 12-lead ECG for diagnosis of ST-segment elevation MI (STEMI) in patients presenting with chest pain in ST LEUIS, an international, multicenter study.

Bruce Jancin/MDedge News

“This study demonstrates that a 12-lead-equivalent ECG obtained using a smartphone coupled with a software application and inexpensive two-wire attachment can identify STEMI versus non-STEMI with an excellent correlation to a traditional 12-lead ECG. This technology holds substantial promise to improve outcomes in STEMI by enabling more rapid diagnosis and treatment anywhere in the world for inexpensive cost,” J. Brent Muhlestein, MD, said while presenting the ST LEUIS results at the American Heart Association scientific sessions.

This technology could provide a long-sought breakthrough in overcoming patient denial and motivating hard-headed individuals with a life-threatening MI to get to the hospital more quickly after symptom onset, instead of initially shrugging off the matter as indigestion or another nuisance. If individuals can use their handy cell phone or smartwatch to quickly obtain an ECG that shows they’re having a STEMI, they’re going to seek medical attention much sooner, with resultant greater salvage of heart muscle, noted Dr. Muhlestein of Intermountain Healthcare in Salt Lake City.

ST LEUIS tested whether a smartphone ECG app developed by AliveCor can accurately diagnose STEMI in patients with chest pain. The study, which took place at Intermountain Medical Center and a handful of other sites associated with the Duke University Cooperative Cardiovascular Society, included 204 patients who presented to EDs with chest pain. They simultaneously received both a standard 12-lead ECG and an ECG obtained using the AliveCor smartphone app. The matched ECG pairs were evaluated separately, both quantitatively and qualitatively, by a blinded panel of experienced cardiologists and classified as STEMI, left bundle branch block, non-STEMI, or uninterpretable. The study population included 92 patients with chest pain and activation of a STEMI protocol and 112 who came through the ED chest pain protocol.

Side-by-side ECG comparisons weren’t attempted in 14 pairs deemed not interpretable. In 13 cases this was because of technical problems with the smartphone ECG, and in the 14th because of ventricular pacing in the standard 12-lead ECG.

STEMI was diagnosed in 22.5% of the study population by 12-lead ECG and in 29.4% by smartphone app. The discrepancy was explained by small voltage differences in the ST-segment elevation which met criteria for STEMI by smartphone but not standard 12-lead ECG in 15 cases.

“It appears that the ST elevation was a little bit more obvious in the smartphone ECG,” Dr. Muhlestein observed.

Left bundle branch block was identified in 5.4% of patients by both methods.

The key performance numbers: The smartphone ECG had a sensitivity of 89%, specificity of 84%, positive predictive value of 70%, and negative predictive value of 95% for diagnosis of STEMI or left bundle branch block. The positive predictive value was diminished by the increased likelihood that the smartphone would call STEMI in discordant cases.

Dr. Muhlestein said that, despite the AliveCor device’s very good correlation with the standard 12-lead ECG, the system needs further tweaking.

“We definitely think this is not ready for prime time. Further refinements of the software and hardware may improve on our study results and broaden potential applications through increased ease of use and reliability. I’m sure smart engineers can make a much more simple, really user-friendly device now that we know it’s actually feasible. I envision a time when you turn it on and it speaks loud and tells you what to do and how to do it – like an AED [automated external defibrillator] – then uploads the ECG to the cloud, interprets it, and tells you whether you should go to the emergency department or not,” Dr. Muhlestein said.

This is a device that’s going to be a boon not only in the United States but also in developing countries, where even people living without electricity or running water often have cell phones, the cardiologist noted.

Dr. Muhlestein reported having no financial conflicts of interest regarding the study, which was sponsored by the participating medical institutions.

bjancin@mdedge.com

CHICAGO – A novel smartphone app performed nearly as well as a standard 12-lead ECG for diagnosis of ST-segment elevation MI (STEMI) in patients presenting with chest pain in ST LEUIS, an international, multicenter study.

Bruce Jancin/MDedge News

“This study demonstrates that a 12-lead-equivalent ECG obtained using a smartphone coupled with a software application and inexpensive two-wire attachment can identify STEMI versus non-STEMI with an excellent correlation to a traditional 12-lead ECG. This technology holds substantial promise to improve outcomes in STEMI by enabling more rapid diagnosis and treatment anywhere in the world for inexpensive cost,” J. Brent Muhlestein, MD, said while presenting the ST LEUIS results at the American Heart Association scientific sessions.

This technology could provide a long-sought breakthrough in overcoming patient denial and motivating hard-headed individuals with a life-threatening MI to get to the hospital more quickly after symptom onset, instead of initially shrugging off the matter as indigestion or another nuisance. If individuals can use their handy cell phone or smartwatch to quickly obtain an ECG that shows they’re having a STEMI, they’re going to seek medical attention much sooner, with resultant greater salvage of heart muscle, noted Dr. Muhlestein of Intermountain Healthcare in Salt Lake City.

ST LEUIS tested whether a smartphone ECG app developed by AliveCor can accurately diagnose STEMI in patients with chest pain. The study, which took place at Intermountain Medical Center and a handful of other sites associated with the Duke University Cooperative Cardiovascular Society, included 204 patients who presented to EDs with chest pain. They simultaneously received both a standard 12-lead ECG and an ECG obtained using the AliveCor smartphone app. The matched ECG pairs were evaluated separately, both quantitatively and qualitatively, by a blinded panel of experienced cardiologists and classified as STEMI, left bundle branch block, non-STEMI, or uninterpretable. The study population included 92 patients with chest pain and activation of a STEMI protocol and 112 who came through the ED chest pain protocol.

Side-by-side ECG comparisons weren’t attempted in 14 pairs deemed not interpretable. In 13 cases this was because of technical problems with the smartphone ECG, and in the 14th because of ventricular pacing in the standard 12-lead ECG.

STEMI was diagnosed in 22.5% of the study population by 12-lead ECG and in 29.4% by smartphone app. The discrepancy was explained by small voltage differences in the ST-segment elevation which met criteria for STEMI by smartphone but not standard 12-lead ECG in 15 cases.

“It appears that the ST elevation was a little bit more obvious in the smartphone ECG,” Dr. Muhlestein observed.

Left bundle branch block was identified in 5.4% of patients by both methods.

The key performance numbers: The smartphone ECG had a sensitivity of 89%, specificity of 84%, positive predictive value of 70%, and negative predictive value of 95% for diagnosis of STEMI or left bundle branch block. The positive predictive value was diminished by the increased likelihood that the smartphone would call STEMI in discordant cases.

Dr. Muhlestein said that, despite the AliveCor device’s very good correlation with the standard 12-lead ECG, the system needs further tweaking.

“We definitely think this is not ready for prime time. Further refinements of the software and hardware may improve on our study results and broaden potential applications through increased ease of use and reliability. I’m sure smart engineers can make a much more simple, really user-friendly device now that we know it’s actually feasible. I envision a time when you turn it on and it speaks loud and tells you what to do and how to do it – like an AED [automated external defibrillator] – then uploads the ECG to the cloud, interprets it, and tells you whether you should go to the emergency department or not,” Dr. Muhlestein said.

This is a device that’s going to be a boon not only in the United States but also in developing countries, where even people living without electricity or running water often have cell phones, the cardiologist noted.

Dr. Muhlestein reported having no financial conflicts of interest regarding the study, which was sponsored by the participating medical institutions.

bjancin@mdedge.com

CHICAGO – A novel smartphone app performed nearly as well as a standard 12-lead ECG for diagnosis of ST-segment elevation MI (STEMI) in patients presenting with chest pain in ST LEUIS, an international, multicenter study.

Bruce Jancin/MDedge News

“This study demonstrates that a 12-lead-equivalent ECG obtained using a smartphone coupled with a software application and inexpensive two-wire attachment can identify STEMI versus non-STEMI with an excellent correlation to a traditional 12-lead ECG. This technology holds substantial promise to improve outcomes in STEMI by enabling more rapid diagnosis and treatment anywhere in the world for inexpensive cost,” J. Brent Muhlestein, MD, said while presenting the ST LEUIS results at the American Heart Association scientific sessions.

This technology could provide a long-sought breakthrough in overcoming patient denial and motivating hard-headed individuals with a life-threatening MI to get to the hospital more quickly after symptom onset, instead of initially shrugging off the matter as indigestion or another nuisance. If individuals can use their handy cell phone or smartwatch to quickly obtain an ECG that shows they’re having a STEMI, they’re going to seek medical attention much sooner, with resultant greater salvage of heart muscle, noted Dr. Muhlestein of Intermountain Healthcare in Salt Lake City.

ST LEUIS tested whether a smartphone ECG app developed by AliveCor can accurately diagnose STEMI in patients with chest pain. The study, which took place at Intermountain Medical Center and a handful of other sites associated with the Duke University Cooperative Cardiovascular Society, included 204 patients who presented to EDs with chest pain. They simultaneously received both a standard 12-lead ECG and an ECG obtained using the AliveCor smartphone app. The matched ECG pairs were evaluated separately, both quantitatively and qualitatively, by a blinded panel of experienced cardiologists and classified as STEMI, left bundle branch block, non-STEMI, or uninterpretable. The study population included 92 patients with chest pain and activation of a STEMI protocol and 112 who came through the ED chest pain protocol.

Side-by-side ECG comparisons weren’t attempted in 14 pairs deemed not interpretable. In 13 cases this was because of technical problems with the smartphone ECG, and in the 14th because of ventricular pacing in the standard 12-lead ECG.

STEMI was diagnosed in 22.5% of the study population by 12-lead ECG and in 29.4% by smartphone app. The discrepancy was explained by small voltage differences in the ST-segment elevation which met criteria for STEMI by smartphone but not standard 12-lead ECG in 15 cases.

“It appears that the ST elevation was a little bit more obvious in the smartphone ECG,” Dr. Muhlestein observed.

Left bundle branch block was identified in 5.4% of patients by both methods.

The key performance numbers: The smartphone ECG had a sensitivity of 89%, specificity of 84%, positive predictive value of 70%, and negative predictive value of 95% for diagnosis of STEMI or left bundle branch block. The positive predictive value was diminished by the increased likelihood that the smartphone would call STEMI in discordant cases.

Dr. Muhlestein said that, despite the AliveCor device’s very good correlation with the standard 12-lead ECG, the system needs further tweaking.

“We definitely think this is not ready for prime time. Further refinements of the software and hardware may improve on our study results and broaden potential applications through increased ease of use and reliability. I’m sure smart engineers can make a much more simple, really user-friendly device now that we know it’s actually feasible. I envision a time when you turn it on and it speaks loud and tells you what to do and how to do it – like an AED [automated external defibrillator] – then uploads the ECG to the cloud, interprets it, and tells you whether you should go to the emergency department or not,” Dr. Muhlestein said.

This is a device that’s going to be a boon not only in the United States but also in developing countries, where even people living without electricity or running water often have cell phones, the cardiologist noted.

Dr. Muhlestein reported having no financial conflicts of interest regarding the study, which was sponsored by the participating medical institutions.

bjancin@mdedge.com

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

mzoler@mdedge.com

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

mzoler@mdedge.com

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

mzoler@mdedge.com

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – Stroke patients in low to middle income care settings may frequently fail to get timely evidence-based treatments when they’re admitted to the hospital and even when they’re discharged, but a large South American study found that an “all-or-none” approach to a multistep quality-improvement program led to a significant increase in therapy adherence and smoking cessation. The results were reported at the American Heart Association scientific sessions.

“A multifaceted quality-improvement intervention did not result in a significant increase in the composite adherence score for evidence-based therapies in patients with acute ischemic stroke [AIS] or transient ischemic attack [TIA],” said M. Julia Machline-Carrion, MD, PhD, principal investigator of the BRIDGE-Stroke study and a cardiologist at the Hospital for Heart in São Paulo. “However, when using a more conservative ‘all-or-none’ approach of complete adherence, the intervention resulted in improved adherence to evidence-based therapies.”

The quality-improvement program also resulted in a significant increase in the use of thrombolysis and uptake in smoking cessation education by study participants, Dr. Machline-Carrion added.

The study randomized 1,624 patients with AIS or TIA to the multifaceted quality-improvement intervention or routine practice. The intervention consisted of a patient identification system (wristband and printed reminders), a therapeutic plan road map and checklist, case management, educational materials, interactive workshops, and periodic audit and feedback reports to each participating cluster. Colored wristbands were to help promptly identify AIS or TIA patients in the emergency department and other departments they may have been sent to later on, such as the ICU, to avoid delays in initiating recommended therapies.

On average, the composite adherence score was 85.3% for those in the intervention group vs. 77.8% for controls, Dr. Machline-Carrion said. The composite adherence score consisted of 10 quality measures, ranging from early antithrombotics and prophylaxis for deep vein thrombosis to anticoagulation for atrial fibrillation or flutter, and smoking cessation education. “There was no statistically significant difference in the composite adherence score between the intervention group and the usual-care group,” she said.

However, when the researchers applied the all-or-none model – that is, complete adherence to all 10 in-hospital quality measures – the results were strikingly different, Dr. Machline-Carrion said. “Patients in the intervention group were more likely to receive all eligible therapies,” she said: 49.2% vs. 25.3%.

“Despite the established efficacy of several interventions for the management of patients with acute ischemic stroke and transient ischemic attack, the uptake of evidence-based measures remains suboptimal, especially in low- and middle-income countries,” Dr. Machline-Carrion said.

The BRIDGE-Stroke study involved 36 hospitals in Brazil, Argentina, and Peru with full emergency department coverage, central nervous system imaging, and access to recombinant tissue plasminogen activator therapies.

Dr. Machline-Carrion disclosed financial relationships with Amgen and Boehringer Ingelheim. The Brazil Ministry of Health was the lead sponsor of the study.

SOURCE: Machline-Carrion MJ et al. AHA scientific sessions, Abstract 19361.

CHICAGO – Stroke patients in low to middle income care settings may frequently fail to get timely evidence-based treatments when they’re admitted to the hospital and even when they’re discharged, but a large South American study found that an “all-or-none” approach to a multistep quality-improvement program led to a significant increase in therapy adherence and smoking cessation. The results were reported at the American Heart Association scientific sessions.

“A multifaceted quality-improvement intervention did not result in a significant increase in the composite adherence score for evidence-based therapies in patients with acute ischemic stroke [AIS] or transient ischemic attack [TIA],” said M. Julia Machline-Carrion, MD, PhD, principal investigator of the BRIDGE-Stroke study and a cardiologist at the Hospital for Heart in São Paulo. “However, when using a more conservative ‘all-or-none’ approach of complete adherence, the intervention resulted in improved adherence to evidence-based therapies.”

The quality-improvement program also resulted in a significant increase in the use of thrombolysis and uptake in smoking cessation education by study participants, Dr. Machline-Carrion added.

The study randomized 1,624 patients with AIS or TIA to the multifaceted quality-improvement intervention or routine practice. The intervention consisted of a patient identification system (wristband and printed reminders), a therapeutic plan road map and checklist, case management, educational materials, interactive workshops, and periodic audit and feedback reports to each participating cluster. Colored wristbands were to help promptly identify AIS or TIA patients in the emergency department and other departments they may have been sent to later on, such as the ICU, to avoid delays in initiating recommended therapies.

On average, the composite adherence score was 85.3% for those in the intervention group vs. 77.8% for controls, Dr. Machline-Carrion said. The composite adherence score consisted of 10 quality measures, ranging from early antithrombotics and prophylaxis for deep vein thrombosis to anticoagulation for atrial fibrillation or flutter, and smoking cessation education. “There was no statistically significant difference in the composite adherence score between the intervention group and the usual-care group,” she said.

However, when the researchers applied the all-or-none model – that is, complete adherence to all 10 in-hospital quality measures – the results were strikingly different, Dr. Machline-Carrion said. “Patients in the intervention group were more likely to receive all eligible therapies,” she said: 49.2% vs. 25.3%.

“Despite the established efficacy of several interventions for the management of patients with acute ischemic stroke and transient ischemic attack, the uptake of evidence-based measures remains suboptimal, especially in low- and middle-income countries,” Dr. Machline-Carrion said.

The BRIDGE-Stroke study involved 36 hospitals in Brazil, Argentina, and Peru with full emergency department coverage, central nervous system imaging, and access to recombinant tissue plasminogen activator therapies.

Dr. Machline-Carrion disclosed financial relationships with Amgen and Boehringer Ingelheim. The Brazil Ministry of Health was the lead sponsor of the study.

SOURCE: Machline-Carrion MJ et al. AHA scientific sessions, Abstract 19361.

CHICAGO – Stroke patients in low to middle income care settings may frequently fail to get timely evidence-based treatments when they’re admitted to the hospital and even when they’re discharged, but a large South American study found that an “all-or-none” approach to a multistep quality-improvement program led to a significant increase in therapy adherence and smoking cessation. The results were reported at the American Heart Association scientific sessions.

“A multifaceted quality-improvement intervention did not result in a significant increase in the composite adherence score for evidence-based therapies in patients with acute ischemic stroke [AIS] or transient ischemic attack [TIA],” said M. Julia Machline-Carrion, MD, PhD, principal investigator of the BRIDGE-Stroke study and a cardiologist at the Hospital for Heart in São Paulo. “However, when using a more conservative ‘all-or-none’ approach of complete adherence, the intervention resulted in improved adherence to evidence-based therapies.”

The quality-improvement program also resulted in a significant increase in the use of thrombolysis and uptake in smoking cessation education by study participants, Dr. Machline-Carrion added.

The study randomized 1,624 patients with AIS or TIA to the multifaceted quality-improvement intervention or routine practice. The intervention consisted of a patient identification system (wristband and printed reminders), a therapeutic plan road map and checklist, case management, educational materials, interactive workshops, and periodic audit and feedback reports to each participating cluster. Colored wristbands were to help promptly identify AIS or TIA patients in the emergency department and other departments they may have been sent to later on, such as the ICU, to avoid delays in initiating recommended therapies.

On average, the composite adherence score was 85.3% for those in the intervention group vs. 77.8% for controls, Dr. Machline-Carrion said. The composite adherence score consisted of 10 quality measures, ranging from early antithrombotics and prophylaxis for deep vein thrombosis to anticoagulation for atrial fibrillation or flutter, and smoking cessation education. “There was no statistically significant difference in the composite adherence score between the intervention group and the usual-care group,” she said.

However, when the researchers applied the all-or-none model – that is, complete adherence to all 10 in-hospital quality measures – the results were strikingly different, Dr. Machline-Carrion said. “Patients in the intervention group were more likely to receive all eligible therapies,” she said: 49.2% vs. 25.3%.

“Despite the established efficacy of several interventions for the management of patients with acute ischemic stroke and transient ischemic attack, the uptake of evidence-based measures remains suboptimal, especially in low- and middle-income countries,” Dr. Machline-Carrion said.

The BRIDGE-Stroke study involved 36 hospitals in Brazil, Argentina, and Peru with full emergency department coverage, central nervous system imaging, and access to recombinant tissue plasminogen activator therapies.

Dr. Machline-Carrion disclosed financial relationships with Amgen and Boehringer Ingelheim. The Brazil Ministry of Health was the lead sponsor of the study.

SOURCE: Machline-Carrion MJ et al. AHA scientific sessions, Abstract 19361.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.

U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.

“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.

The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.


Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).

“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.

His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.

In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.

mzoler@mdedge.com

SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.

CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.

U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.

“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.

The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.


Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).

“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.

His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.

In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.

mzoler@mdedge.com

SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.

CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.

U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.

“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.

The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.


Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).

“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.

His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.

In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.

mzoler@mdedge.com

SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.

CHICAGO – Both methotrexate and canakinumab are anti-inflammatory drugs, but only canakinumab cut the incidence of cardiovascular disease events in a major clinical trial, CANTOS. A second big trial designed to parallel CANTOS tested methotrexate in roughly the same way and found it produced no cardiovascular disease benefit among high-risk patients.

Mitchel L. Zoler/MDedge News

The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) results with canakinumab and the new results with methotrexate “demonstrate that inflammation inhibition [with canakinumab] can significantly reduce cardiovascular event rates independent of lipid lowering and blood pressure reduction,” Paul M. Ridker, MD, said at the American Heart Association scientific sessions. But, “inhibition of the IL [interleukin]–1 beta to IL-6 to CRP [C-reactive protein] pathway of innate immunity appears to be important for atheroprotection,” and was something methotrexate couldn’t deliver, concluded Dr. Ridker, a professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.

The new results he reported showed that weekly treatment with a single, oral, 15- to 20-mg dose of methotrexate not only had no effect on cardiovascular events but also had no discernible impact on serum levels of IL-1beta (IL-1B), IL-6, or high sensitivity (hs) CRP, in contrast to canakinumab, which Dr. Ridker took as evidence that this inflammatory pathway links to the pathophysiology of atherosclerotic cardiovascular disease.

CIRT (Cardiovascular Inflammation Reduction Trial) randomized 4,786 patients at 417 centers in the United States or Canada. Enrolled patients had to have a history of an MI or documented multivessel coronary disease, and also had to have type 2 diabetes, metabolic syndrome, or both. All patients were maintained on optimized dosages of a statin, aspirin, a beta-blocker, and an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. All patients also received 1 mg folate daily. Randomization assigned patients to either receive 15-20 mg methotrexate orally once a week or placebo.


CIRT stopped prematurely because of futility after a median follow-up of 2.3 years. At that time, the incidence of one of two primary endpoints, the combination of cardiovascular death, nonfatal MI, and nonfatal stroke was 3.46/100 person-years with methotrexate treatment and 3.43/100 person-years with placebo, a difference that was not statistically significant. The incidence of the second primary endpoint, which combined the first three types of events plus hospitalization for unstable angina that led to urgent coronary revascularization, occurred in 4.13/100 person-years with methotrexate and 4.31/100 person years with placebo, also a difference that was not statistically significant. Concurrently with this report, the results were published online (N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1809798).

Analysis of inflammatory markers in the blood after 8 months on treatment showed that methotrexate had no effect on levels of IL-1B, IL-6, and hsCRP. Methotrexate’s lack of an effect on these markers as well as the absence of an effect on cardiovascular disease events contrasted sharply with results that Dr. Ridker and his associates reported a little more than a year earlier in CANTOS. The study’s investigators randomized 10,061 patients with a history of an MI and an elevated serum level of hsCRP, at least 2.0 mg/L. After a median follow-up of 3.7 years, treatment with 150 mg of canakinumab injected subcutaneously once every 3 months produced a 15% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, compared with patients treated with placebo, a statistically significant between-group difference (N Engl J Med. 2017 Sep 21;377[12]:1119-31). Canakinumab had no impact on LDL cholesterol levels, but lowered hsCRP levels by more than a third. Dr. Ridker and his associates designed the CIRT and CANTOS trials “in parallel,” he said, and the CIRT results using methotrexate provided a “neutral control” to complement the positive results from canakinumab in CANTOS,

Given its high cost, canakinumab (Ilaris) is not an obviously practical option for treating patients similar to those enrolled in CANTOS, so other candidate agents that inhibit the IL-1B, IL-6, CRP inflammatory pathway are now under study, Dr. Ridker said in an interview. The mechanism of methotrexate’s inhibition of inflammation is unknown, but clearly does not involve this pathway; it may be mediated by adenosine, Dr. Ridker suggested. Canakinumab has Food and Drug Administration approval for treating systemic juvenile idiopathic arthritis and a handful of additional, low-prevalence diseases. Novartis, the company that markets canakinumab, made a submission to the Food and Drug Administration seeking an indication for prevention of cardiovascular disease based on the CANTOS results, and the company said in October 2018 that the FDA denied this request.

The CIRT results also showed a previously unseen signal of a possible safety issue with the tested methotrexate regimen. The incidence of non–basal cell skin cancer was 0.65/100 person-years with methotrexate, compared with 0.24/100 person-years with placebo, a statistically significant difference. Until now, no one had reported a link like this and it requires further analysis, Dr. Ridker said.

CIRT received no commercial funding. Dr. Ridker has been a consultant to Corvidia, Inflazome, and Novartis; he has received research funding from Kowa and Novartis; and his work led to a patent held by Brigham and Women’s Hospital for inflammatory biomarkers licensed to Siemens and AstraZeneca.

mzoler@mdedge.com

SOURCE: Ridker P et al. AHA scientific sessions, Abstract 17778.

CHICAGO – Both methotrexate and canakinumab are anti-inflammatory drugs, but only canakinumab cut the incidence of cardiovascular disease events in a major clinical trial, CANTOS. A second big trial designed to parallel CANTOS tested methotrexate in roughly the same way and found it produced no cardiovascular disease benefit among high-risk patients.

Mitchel L. Zoler/MDedge News

The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) results with canakinumab and the new results with methotrexate “demonstrate that inflammation inhibition [with canakinumab] can significantly reduce cardiovascular event rates independent of lipid lowering and blood pressure reduction,” Paul M. Ridker, MD, said at the American Heart Association scientific sessions. But, “inhibition of the IL [interleukin]–1 beta to IL-6 to CRP [C-reactive protein] pathway of innate immunity appears to be important for atheroprotection,” and was something methotrexate couldn’t deliver, concluded Dr. Ridker, a professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.

The new results he reported showed that weekly treatment with a single, oral, 15- to 20-mg dose of methotrexate not only had no effect on cardiovascular events but also had no discernible impact on serum levels of IL-1beta (IL-1B), IL-6, or high sensitivity (hs) CRP, in contrast to canakinumab, which Dr. Ridker took as evidence that this inflammatory pathway links to the pathophysiology of atherosclerotic cardiovascular disease.

CIRT (Cardiovascular Inflammation Reduction Trial) randomized 4,786 patients at 417 centers in the United States or Canada. Enrolled patients had to have a history of an MI or documented multivessel coronary disease, and also had to have type 2 diabetes, metabolic syndrome, or both. All patients were maintained on optimized dosages of a statin, aspirin, a beta-blocker, and an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. All patients also received 1 mg folate daily. Randomization assigned patients to either receive 15-20 mg methotrexate orally once a week or placebo.


CIRT stopped prematurely because of futility after a median follow-up of 2.3 years. At that time, the incidence of one of two primary endpoints, the combination of cardiovascular death, nonfatal MI, and nonfatal stroke was 3.46/100 person-years with methotrexate treatment and 3.43/100 person-years with placebo, a difference that was not statistically significant. The incidence of the second primary endpoint, which combined the first three types of events plus hospitalization for unstable angina that led to urgent coronary revascularization, occurred in 4.13/100 person-years with methotrexate and 4.31/100 person years with placebo, also a difference that was not statistically significant. Concurrently with this report, the results were published online (N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1809798).

Analysis of inflammatory markers in the blood after 8 months on treatment showed that methotrexate had no effect on levels of IL-1B, IL-6, and hsCRP. Methotrexate’s lack of an effect on these markers as well as the absence of an effect on cardiovascular disease events contrasted sharply with results that Dr. Ridker and his associates reported a little more than a year earlier in CANTOS. The study’s investigators randomized 10,061 patients with a history of an MI and an elevated serum level of hsCRP, at least 2.0 mg/L. After a median follow-up of 3.7 years, treatment with 150 mg of canakinumab injected subcutaneously once every 3 months produced a 15% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, compared with patients treated with placebo, a statistically significant between-group difference (N Engl J Med. 2017 Sep 21;377[12]:1119-31). Canakinumab had no impact on LDL cholesterol levels, but lowered hsCRP levels by more than a third. Dr. Ridker and his associates designed the CIRT and CANTOS trials “in parallel,” he said, and the CIRT results using methotrexate provided a “neutral control” to complement the positive results from canakinumab in CANTOS,

Given its high cost, canakinumab (Ilaris) is not an obviously practical option for treating patients similar to those enrolled in CANTOS, so other candidate agents that inhibit the IL-1B, IL-6, CRP inflammatory pathway are now under study, Dr. Ridker said in an interview. The mechanism of methotrexate’s inhibition of inflammation is unknown, but clearly does not involve this pathway; it may be mediated by adenosine, Dr. Ridker suggested. Canakinumab has Food and Drug Administration approval for treating systemic juvenile idiopathic arthritis and a handful of additional, low-prevalence diseases. Novartis, the company that markets canakinumab, made a submission to the Food and Drug Administration seeking an indication for prevention of cardiovascular disease based on the CANTOS results, and the company said in October 2018 that the FDA denied this request.

The CIRT results also showed a previously unseen signal of a possible safety issue with the tested methotrexate regimen. The incidence of non–basal cell skin cancer was 0.65/100 person-years with methotrexate, compared with 0.24/100 person-years with placebo, a statistically significant difference. Until now, no one had reported a link like this and it requires further analysis, Dr. Ridker said.

CIRT received no commercial funding. Dr. Ridker has been a consultant to Corvidia, Inflazome, and Novartis; he has received research funding from Kowa and Novartis; and his work led to a patent held by Brigham and Women’s Hospital for inflammatory biomarkers licensed to Siemens and AstraZeneca.

mzoler@mdedge.com

SOURCE: Ridker P et al. AHA scientific sessions, Abstract 17778.

CHICAGO – Both methotrexate and canakinumab are anti-inflammatory drugs, but only canakinumab cut the incidence of cardiovascular disease events in a major clinical trial, CANTOS. A second big trial designed to parallel CANTOS tested methotrexate in roughly the same way and found it produced no cardiovascular disease benefit among high-risk patients.

Mitchel L. Zoler/MDedge News

The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) results with canakinumab and the new results with methotrexate “demonstrate that inflammation inhibition [with canakinumab] can significantly reduce cardiovascular event rates independent of lipid lowering and blood pressure reduction,” Paul M. Ridker, MD, said at the American Heart Association scientific sessions. But, “inhibition of the IL [interleukin]–1 beta to IL-6 to CRP [C-reactive protein] pathway of innate immunity appears to be important for atheroprotection,” and was something methotrexate couldn’t deliver, concluded Dr. Ridker, a professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.

The new results he reported showed that weekly treatment with a single, oral, 15- to 20-mg dose of methotrexate not only had no effect on cardiovascular events but also had no discernible impact on serum levels of IL-1beta (IL-1B), IL-6, or high sensitivity (hs) CRP, in contrast to canakinumab, which Dr. Ridker took as evidence that this inflammatory pathway links to the pathophysiology of atherosclerotic cardiovascular disease.

CIRT (Cardiovascular Inflammation Reduction Trial) randomized 4,786 patients at 417 centers in the United States or Canada. Enrolled patients had to have a history of an MI or documented multivessel coronary disease, and also had to have type 2 diabetes, metabolic syndrome, or both. All patients were maintained on optimized dosages of a statin, aspirin, a beta-blocker, and an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. All patients also received 1 mg folate daily. Randomization assigned patients to either receive 15-20 mg methotrexate orally once a week or placebo.


CIRT stopped prematurely because of futility after a median follow-up of 2.3 years. At that time, the incidence of one of two primary endpoints, the combination of cardiovascular death, nonfatal MI, and nonfatal stroke was 3.46/100 person-years with methotrexate treatment and 3.43/100 person-years with placebo, a difference that was not statistically significant. The incidence of the second primary endpoint, which combined the first three types of events plus hospitalization for unstable angina that led to urgent coronary revascularization, occurred in 4.13/100 person-years with methotrexate and 4.31/100 person years with placebo, also a difference that was not statistically significant. Concurrently with this report, the results were published online (N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1809798).

Analysis of inflammatory markers in the blood after 8 months on treatment showed that methotrexate had no effect on levels of IL-1B, IL-6, and hsCRP. Methotrexate’s lack of an effect on these markers as well as the absence of an effect on cardiovascular disease events contrasted sharply with results that Dr. Ridker and his associates reported a little more than a year earlier in CANTOS. The study’s investigators randomized 10,061 patients with a history of an MI and an elevated serum level of hsCRP, at least 2.0 mg/L. After a median follow-up of 3.7 years, treatment with 150 mg of canakinumab injected subcutaneously once every 3 months produced a 15% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, compared with patients treated with placebo, a statistically significant between-group difference (N Engl J Med. 2017 Sep 21;377[12]:1119-31). Canakinumab had no impact on LDL cholesterol levels, but lowered hsCRP levels by more than a third. Dr. Ridker and his associates designed the CIRT and CANTOS trials “in parallel,” he said, and the CIRT results using methotrexate provided a “neutral control” to complement the positive results from canakinumab in CANTOS,

Given its high cost, canakinumab (Ilaris) is not an obviously practical option for treating patients similar to those enrolled in CANTOS, so other candidate agents that inhibit the IL-1B, IL-6, CRP inflammatory pathway are now under study, Dr. Ridker said in an interview. The mechanism of methotrexate’s inhibition of inflammation is unknown, but clearly does not involve this pathway; it may be mediated by adenosine, Dr. Ridker suggested. Canakinumab has Food and Drug Administration approval for treating systemic juvenile idiopathic arthritis and a handful of additional, low-prevalence diseases. Novartis, the company that markets canakinumab, made a submission to the Food and Drug Administration seeking an indication for prevention of cardiovascular disease based on the CANTOS results, and the company said in October 2018 that the FDA denied this request.

The CIRT results also showed a previously unseen signal of a possible safety issue with the tested methotrexate regimen. The incidence of non–basal cell skin cancer was 0.65/100 person-years with methotrexate, compared with 0.24/100 person-years with placebo, a statistically significant difference. Until now, no one had reported a link like this and it requires further analysis, Dr. Ridker said.

CIRT received no commercial funding. Dr. Ridker has been a consultant to Corvidia, Inflazome, and Novartis; he has received research funding from Kowa and Novartis; and his work led to a patent held by Brigham and Women’s Hospital for inflammatory biomarkers licensed to Siemens and AstraZeneca.

mzoler@mdedge.com

SOURCE: Ridker P et al. AHA scientific sessions, Abstract 17778.