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BARCELONA – Intensive perioperative statin therapy in patients undergoing CABG surgery doesn’t protect against postop atrial fibrillation or myocardial injury, according to a large randomized clinical trial hailed as the "definitive" study addressing this issue.
"There are many reasons why these patients should be put on statin treatment, but the prevention of postop complications is not one of them," Dr. Barbara Casadei said in presenting the findings of the Statin Therapy in Cardiac Surgery (STICS) trial at the annual congress of the European Society of Cardiology.
The STICS results are at odds with conventional wisdom. ESC guidelines give a favorable class IIa, level of evidence B recommendation that "statins should be considered for prevention of new-onset atrial fibrillation after coronary artery bypass grafting, either isolated or in combination with valvular interventions."
"STICS was a very carefully conducted, large scale, robust study that I think has definitely closed the door on this issue," commented Dr. Keith A.A. Fox, professor of cardiology at the University of Edinburgh and chair of the scientific and clinical program committee at ESC Congress 2014.
STICS was a double-blind prospective trial in which 1,922 patients scheduled for elective CABG were randomized to 20 mg per day of rosuvastatin (Crestor) or placebo starting up to 8 days prior to surgery and continued for 5 days postop. All participants were in sinus rhythm preoperatively, with no history of AF, said Dr. Casadei, professor of cardiovascular medicine at the University of Oxford, England.
The two coprimary endpoints in STICS were the incidence of new-onset AF during 5 days of postop Holter monitoring, and evidence of postop myocardial injury as demonstrated in serial troponin I assays.
Postop AF occurred in 21% of those given high-intensity therapy with rosuvastatin and 20% of placebo-treated controls. There was no subgroup where rosuvastatin was protective (see graphic).
Troponin I measurements obtained 6, 24, 48, and 120 hours postop showed areas under the curve that were superimposable in the two study groups, meaning perioperative high-dose statin therapy provided absolutely no protection against postop cardiac muscle injury.
Mean hospital length of stay and ICU time didn’t differ between the two groups, either.
The impetus for conducting STICS was recognition that the guidelines’ endorsement of perioperative high-dose statin therapy in conjunction with cardiac surgery was based upon a series of small randomized trials with serious limitations. Although the results of a meta-analysis of the 14 prior trials looked impressive at first glance – a 17% incidence of postop AF in statin-treated patients, compared with 30% in controls, for a near-halving of the risk of this important complication – these 14 studies totaled 1,300 patients, and there were many methodologic shortcomings.
The STICS researchers hypothesized that a large, well-designed trial – bigger than all previous studies combined – would shore up the previously shaky supporting evidence and perhaps provide grounds for statins to win a new indication from regulatory agencies. Post-CABG AF is associated with a doubled risk of stroke and mortality, and excess hospital costs of $8,000-$18,000 dollars per patient.
Discussant Dr. Paulus Kirchhof, a member of the task force that developed the current ESC guidelines (Europace 2010;12:1360-420), said those guidelines now clearly need to be revisited. Beyond that, he added, STICS provides important new contributions in understanding the pathophysiology of AF.
"We know that AF is caused by several vicious circles, and we believe that inflammation could influence those and cause AF. And we also thought that postop AF was the condition where inflammation plays the biggest role. Based upon the negative results with this anti-inflammatory intervention, I think we have to question this concept a bit," said Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham, England.
Dr. Casadei countered that she’s not ready to write off postop inflammation entirely as a major trigger of new-onset AF following CABG.
"The inflammation is there. We know from experimental work in animals that there is a strong association between inflammation and postop atrial fibrillation, but whether the association is causal, I think, is still debated. However, it may be that the anti-inflammatory effect of statins is not sufficiently strong to actually prevent this complication," she said.
Discussant Dr. Steven Nissen praised STICS as "an outstanding trial."
"I also think there’s a terribly important lesson here, which is the power of self-delusion in medicine. When we base our guidelines on small, poorly controlled trials, we are often making mistakes. This is one of countless examples where when someone finally does a careful, thoughtful trial, we find out that something that people believe just isn’t true. We can’t cut corners with evidence. We need good randomized trials," declared Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.
The STICS trial was funded primarily by the British Heart Foundation, the Oxford Biomedical Research Center, and the UK Medical Research Council. In addition, Dr. Casadei reported receiving an unrestricted grant from AstraZeneca in conjunction with the trial.
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| Dr. Hiren Shah |
There are two key lessons from the results of the STICS trial. First, extrapolation of results from biochemical pathways and measured cellular markers does not always translate into meaningful clinical outcomes. Thus, it has long been known from several large trials that statin therapy effectively and rapidly lowers CRP levels both in hyper- and normocholesterolemic patients and that statins are effective in decreasing systemic inflammation. It has also been known that inflammation contributes to the development and maintenance of AF, so it was postulated that by improving endothelial nitric oxide availability, reducing inflammation, and decreasing oxidative stress, and through neurohormonal activation, statins would reduce the incidence of post-op AF. This link was so strong that clinical guidelines adopted limited data from small trials to make treatment recommendations.
This leads us to consider the second key lesson from this study. Trials with small sample size, even when combined across many other trials (1,300 patients were involved across 14 trials in this case), do not always yield reliable results, especially when they have significant limitations, notably not always being blind and having been performed in statin-naive patients only. The large, randomized, and well-designed STICS trial puts to rest an important issue, given the high prevalence of AF after cardiac surgery, which is associated with a longer length of stay, an increased risk of stroke, higher mortality, and greater costs, and should prompt us to consider further evaluation of different strategies to reduce this significant complication.
Dr. Hiren Shah is medical director of the medicine and cardiac telemetry hospitalist unit at Northwestern Memorial Hospital in Chicago and an adviser to Hospitalist News. He is the national chair of the Clinician Committee for ACP’s Initiative on Stroke Prevention and Atrial Fibrillation and is the lead physician for the Society of Hospital Medicine’s National Atrial Fibrillation Initiative.
|
| Dr. Hiren Shah |
There are two key lessons from the results of the STICS trial. First, extrapolation of results from biochemical pathways and measured cellular markers does not always translate into meaningful clinical outcomes. Thus, it has long been known from several large trials that statin therapy effectively and rapidly lowers CRP levels both in hyper- and normocholesterolemic patients and that statins are effective in decreasing systemic inflammation. It has also been known that inflammation contributes to the development and maintenance of AF, so it was postulated that by improving endothelial nitric oxide availability, reducing inflammation, and decreasing oxidative stress, and through neurohormonal activation, statins would reduce the incidence of post-op AF. This link was so strong that clinical guidelines adopted limited data from small trials to make treatment recommendations.
This leads us to consider the second key lesson from this study. Trials with small sample size, even when combined across many other trials (1,300 patients were involved across 14 trials in this case), do not always yield reliable results, especially when they have significant limitations, notably not always being blind and having been performed in statin-naive patients only. The large, randomized, and well-designed STICS trial puts to rest an important issue, given the high prevalence of AF after cardiac surgery, which is associated with a longer length of stay, an increased risk of stroke, higher mortality, and greater costs, and should prompt us to consider further evaluation of different strategies to reduce this significant complication.
Dr. Hiren Shah is medical director of the medicine and cardiac telemetry hospitalist unit at Northwestern Memorial Hospital in Chicago and an adviser to Hospitalist News. He is the national chair of the Clinician Committee for ACP’s Initiative on Stroke Prevention and Atrial Fibrillation and is the lead physician for the Society of Hospital Medicine’s National Atrial Fibrillation Initiative.
|
| Dr. Hiren Shah |
There are two key lessons from the results of the STICS trial. First, extrapolation of results from biochemical pathways and measured cellular markers does not always translate into meaningful clinical outcomes. Thus, it has long been known from several large trials that statin therapy effectively and rapidly lowers CRP levels both in hyper- and normocholesterolemic patients and that statins are effective in decreasing systemic inflammation. It has also been known that inflammation contributes to the development and maintenance of AF, so it was postulated that by improving endothelial nitric oxide availability, reducing inflammation, and decreasing oxidative stress, and through neurohormonal activation, statins would reduce the incidence of post-op AF. This link was so strong that clinical guidelines adopted limited data from small trials to make treatment recommendations.
This leads us to consider the second key lesson from this study. Trials with small sample size, even when combined across many other trials (1,300 patients were involved across 14 trials in this case), do not always yield reliable results, especially when they have significant limitations, notably not always being blind and having been performed in statin-naive patients only. The large, randomized, and well-designed STICS trial puts to rest an important issue, given the high prevalence of AF after cardiac surgery, which is associated with a longer length of stay, an increased risk of stroke, higher mortality, and greater costs, and should prompt us to consider further evaluation of different strategies to reduce this significant complication.
Dr. Hiren Shah is medical director of the medicine and cardiac telemetry hospitalist unit at Northwestern Memorial Hospital in Chicago and an adviser to Hospitalist News. He is the national chair of the Clinician Committee for ACP’s Initiative on Stroke Prevention and Atrial Fibrillation and is the lead physician for the Society of Hospital Medicine’s National Atrial Fibrillation Initiative.
BARCELONA – Intensive perioperative statin therapy in patients undergoing CABG surgery doesn’t protect against postop atrial fibrillation or myocardial injury, according to a large randomized clinical trial hailed as the "definitive" study addressing this issue.
"There are many reasons why these patients should be put on statin treatment, but the prevention of postop complications is not one of them," Dr. Barbara Casadei said in presenting the findings of the Statin Therapy in Cardiac Surgery (STICS) trial at the annual congress of the European Society of Cardiology.
The STICS results are at odds with conventional wisdom. ESC guidelines give a favorable class IIa, level of evidence B recommendation that "statins should be considered for prevention of new-onset atrial fibrillation after coronary artery bypass grafting, either isolated or in combination with valvular interventions."
"STICS was a very carefully conducted, large scale, robust study that I think has definitely closed the door on this issue," commented Dr. Keith A.A. Fox, professor of cardiology at the University of Edinburgh and chair of the scientific and clinical program committee at ESC Congress 2014.
STICS was a double-blind prospective trial in which 1,922 patients scheduled for elective CABG were randomized to 20 mg per day of rosuvastatin (Crestor) or placebo starting up to 8 days prior to surgery and continued for 5 days postop. All participants were in sinus rhythm preoperatively, with no history of AF, said Dr. Casadei, professor of cardiovascular medicine at the University of Oxford, England.
The two coprimary endpoints in STICS were the incidence of new-onset AF during 5 days of postop Holter monitoring, and evidence of postop myocardial injury as demonstrated in serial troponin I assays.
Postop AF occurred in 21% of those given high-intensity therapy with rosuvastatin and 20% of placebo-treated controls. There was no subgroup where rosuvastatin was protective (see graphic).
Troponin I measurements obtained 6, 24, 48, and 120 hours postop showed areas under the curve that were superimposable in the two study groups, meaning perioperative high-dose statin therapy provided absolutely no protection against postop cardiac muscle injury.
Mean hospital length of stay and ICU time didn’t differ between the two groups, either.
The impetus for conducting STICS was recognition that the guidelines’ endorsement of perioperative high-dose statin therapy in conjunction with cardiac surgery was based upon a series of small randomized trials with serious limitations. Although the results of a meta-analysis of the 14 prior trials looked impressive at first glance – a 17% incidence of postop AF in statin-treated patients, compared with 30% in controls, for a near-halving of the risk of this important complication – these 14 studies totaled 1,300 patients, and there were many methodologic shortcomings.
The STICS researchers hypothesized that a large, well-designed trial – bigger than all previous studies combined – would shore up the previously shaky supporting evidence and perhaps provide grounds for statins to win a new indication from regulatory agencies. Post-CABG AF is associated with a doubled risk of stroke and mortality, and excess hospital costs of $8,000-$18,000 dollars per patient.
Discussant Dr. Paulus Kirchhof, a member of the task force that developed the current ESC guidelines (Europace 2010;12:1360-420), said those guidelines now clearly need to be revisited. Beyond that, he added, STICS provides important new contributions in understanding the pathophysiology of AF.
"We know that AF is caused by several vicious circles, and we believe that inflammation could influence those and cause AF. And we also thought that postop AF was the condition where inflammation plays the biggest role. Based upon the negative results with this anti-inflammatory intervention, I think we have to question this concept a bit," said Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham, England.
Dr. Casadei countered that she’s not ready to write off postop inflammation entirely as a major trigger of new-onset AF following CABG.
"The inflammation is there. We know from experimental work in animals that there is a strong association between inflammation and postop atrial fibrillation, but whether the association is causal, I think, is still debated. However, it may be that the anti-inflammatory effect of statins is not sufficiently strong to actually prevent this complication," she said.
Discussant Dr. Steven Nissen praised STICS as "an outstanding trial."
"I also think there’s a terribly important lesson here, which is the power of self-delusion in medicine. When we base our guidelines on small, poorly controlled trials, we are often making mistakes. This is one of countless examples where when someone finally does a careful, thoughtful trial, we find out that something that people believe just isn’t true. We can’t cut corners with evidence. We need good randomized trials," declared Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.
The STICS trial was funded primarily by the British Heart Foundation, the Oxford Biomedical Research Center, and the UK Medical Research Council. In addition, Dr. Casadei reported receiving an unrestricted grant from AstraZeneca in conjunction with the trial.
BARCELONA – Intensive perioperative statin therapy in patients undergoing CABG surgery doesn’t protect against postop atrial fibrillation or myocardial injury, according to a large randomized clinical trial hailed as the "definitive" study addressing this issue.
"There are many reasons why these patients should be put on statin treatment, but the prevention of postop complications is not one of them," Dr. Barbara Casadei said in presenting the findings of the Statin Therapy in Cardiac Surgery (STICS) trial at the annual congress of the European Society of Cardiology.
The STICS results are at odds with conventional wisdom. ESC guidelines give a favorable class IIa, level of evidence B recommendation that "statins should be considered for prevention of new-onset atrial fibrillation after coronary artery bypass grafting, either isolated or in combination with valvular interventions."
"STICS was a very carefully conducted, large scale, robust study that I think has definitely closed the door on this issue," commented Dr. Keith A.A. Fox, professor of cardiology at the University of Edinburgh and chair of the scientific and clinical program committee at ESC Congress 2014.
STICS was a double-blind prospective trial in which 1,922 patients scheduled for elective CABG were randomized to 20 mg per day of rosuvastatin (Crestor) or placebo starting up to 8 days prior to surgery and continued for 5 days postop. All participants were in sinus rhythm preoperatively, with no history of AF, said Dr. Casadei, professor of cardiovascular medicine at the University of Oxford, England.
The two coprimary endpoints in STICS were the incidence of new-onset AF during 5 days of postop Holter monitoring, and evidence of postop myocardial injury as demonstrated in serial troponin I assays.
Postop AF occurred in 21% of those given high-intensity therapy with rosuvastatin and 20% of placebo-treated controls. There was no subgroup where rosuvastatin was protective (see graphic).
Troponin I measurements obtained 6, 24, 48, and 120 hours postop showed areas under the curve that were superimposable in the two study groups, meaning perioperative high-dose statin therapy provided absolutely no protection against postop cardiac muscle injury.
Mean hospital length of stay and ICU time didn’t differ between the two groups, either.
The impetus for conducting STICS was recognition that the guidelines’ endorsement of perioperative high-dose statin therapy in conjunction with cardiac surgery was based upon a series of small randomized trials with serious limitations. Although the results of a meta-analysis of the 14 prior trials looked impressive at first glance – a 17% incidence of postop AF in statin-treated patients, compared with 30% in controls, for a near-halving of the risk of this important complication – these 14 studies totaled 1,300 patients, and there were many methodologic shortcomings.
The STICS researchers hypothesized that a large, well-designed trial – bigger than all previous studies combined – would shore up the previously shaky supporting evidence and perhaps provide grounds for statins to win a new indication from regulatory agencies. Post-CABG AF is associated with a doubled risk of stroke and mortality, and excess hospital costs of $8,000-$18,000 dollars per patient.
Discussant Dr. Paulus Kirchhof, a member of the task force that developed the current ESC guidelines (Europace 2010;12:1360-420), said those guidelines now clearly need to be revisited. Beyond that, he added, STICS provides important new contributions in understanding the pathophysiology of AF.
"We know that AF is caused by several vicious circles, and we believe that inflammation could influence those and cause AF. And we also thought that postop AF was the condition where inflammation plays the biggest role. Based upon the negative results with this anti-inflammatory intervention, I think we have to question this concept a bit," said Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham, England.
Dr. Casadei countered that she’s not ready to write off postop inflammation entirely as a major trigger of new-onset AF following CABG.
"The inflammation is there. We know from experimental work in animals that there is a strong association between inflammation and postop atrial fibrillation, but whether the association is causal, I think, is still debated. However, it may be that the anti-inflammatory effect of statins is not sufficiently strong to actually prevent this complication," she said.
Discussant Dr. Steven Nissen praised STICS as "an outstanding trial."
"I also think there’s a terribly important lesson here, which is the power of self-delusion in medicine. When we base our guidelines on small, poorly controlled trials, we are often making mistakes. This is one of countless examples where when someone finally does a careful, thoughtful trial, we find out that something that people believe just isn’t true. We can’t cut corners with evidence. We need good randomized trials," declared Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.
The STICS trial was funded primarily by the British Heart Foundation, the Oxford Biomedical Research Center, and the UK Medical Research Council. In addition, Dr. Casadei reported receiving an unrestricted grant from AstraZeneca in conjunction with the trial.
AT THE ESC CONGRESS 2014
Key clinical point: Perioperative statin therapy in patients undergoing CABG failed to protect against new-onset postop atrial fibrillation.
Major finding: The incidence of postop atrial fibrillation within 5 days post-CABG was 21% in patients randomized to 20 mg/day of rosuvastatin and 20% in placebo-treated controls.
Data source: The multicenter STICS trial included 1,922 randomized patients scheduled for elective CABG.
Disclosures: STICS was funded by the British Heart Foundation, the Oxford Biomedical Research Center, and the UK Medical Research Council. The presenter reported having received a research grant from AstraZeneca.
