Joyeeta Dastidar, MD

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

For more physician reviews of HM-related literature, visit our website.

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

For more physician reviews of HM-related literature, visit our website.

Clinical question: What is the prognostic influence of atrial fibrillation in patients with acute myocardial infarction?

Background: There have been conflicting reports regarding the prognostic impact of atrial fibrillation (AF) in patients with acute myocardial infarction (MI). This study represents the first meta-analysis performed to quantify the mortality risk associated with AF in MI patients.

Study design: Meta-analysis of observational studies.

Setting: Forty-three studies involving 278,854 patients diagnosed with MI from 1972 to 2000.

Synopsis: The odds ratio (OR) of mortality associated with AF in MI patients was 1.46 (95% confidence interval, 1.35 to 1.58, I2=76%, 23 studies). Although there was significant heterogeneity in included studies, in subgroup analysis, the significant association between AF and mortality was present whether the AF was new (defined as occurring for the first time within one week of MI) with OR of 1.37 (95% confidence interval, 1.26 to 1.49; I2=28%, nine studies) or old (defined as pre-existing before the MI admission) with OR of 1.28 (95% confidence interval, 1.16 to 1.40, I2=24%, four studies). Sensitivity analyses performed by pooling studies according to follow-up duration and adjustment for confounding clinical factors had little effect on the estimates.

Bottom line: AF was associated with increased mortality in patients with MI regardless of the timing of AF development.

Citation: Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction. Circulation. 2011;123:1587-1593.

For more physician reviews of HM-related literature, visit our website.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study
2. CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction
3. Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia
4. CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation
5. Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
6. MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
7. New Left Bundle Branch Block Does Not Predict MI
8. Acute Beta-Blocker Therapy for MI Increased Risk of Shock

PCI Not Inferior to CABG in Left Main Coronary Artery Stenosis at One Year, But Requires Further Study

Clinical question: Is percutaneous coronary intervention (PCI) an acceptable alternative to coronary artery bypass grafting (CABG) in unprotected left main coronary artery disease (CAD)?

Background: The current standard of care for unprotected left main CAD is CABG. A sub-study from a large randomized trial suggests that PCI might be an alternative to CABG for patients with left main CAD. Outcomes after the two treatments have not been directly compared in an appropriately powered trial.

Study design: Prospective, open-label, randomized trial powered for noninferiority.

Setting: Thirteen sites in South Korea.

Synopsis: Six hundred patients with newly diagnosed left main disease with >50% stenosis were randomized to PCI with a sirolimus-eluting stent versus CABG. The primary endpoint of major adverse cardiac or cerebrovascular events occurred in 8.7% in the PCI group and 6.7% in the CABG group at one year (absolute risk difference 2 percentage points, 95% CI, -1.6 to 5.6; P=0.01), which was considered noninferior.

However, ischemia-driven target-vessel revascularization occurred in significantly more patients in the PCI group than in the CABG group. The wide noninferiority margin was due to an unexpectedly low rate of events, thus underpowering the study. Also, study duration was only two years.

Bottom line: PCI with a sirolimus-eluting stent was noninferior to CABG for unprotected left main CAD in this study, but the wide noninferiority margin and limited follow-up duration limit clinical application.

Reference: Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-1727.

CABG Did Not Decrease Mortality in Patients with CAD and Left Ventricular Dysfunction

Clinical question: What role does coronary-artery bypass grafting (CABG) have in the treatment of patients with both coronary artery disease (CAD) and heart failure?

Background: Although CAD is the most common cause of heart failure, early trials that evaluated the use of CABG in relieving angina excluded patients who had left ventricular (LV) dysfunction with ejection fraction <35%. It is unknown whether CABG adds mortality benefit to intensive medical treatment in patients with CAD and LV dysfunction.

Study design: Multicenter, nonblinded, randomized trial.

Setting: One hundred twenty-seven sites in 26 countries.

Synopsis: From July 2002 to May 2007, 1,212 patients with known CAD amenable to CABG and LV ejection fraction <35% were randomized to medical therapy alone versus CABG plus medical therapy with an average follow-up of five years. The primary outcome of death from any cause occurred in 41% of the medical-therapy-alone group and 36% of the CABG-plus-medical-therapy group (hazard ratio with CABG 0.86; 95% CI 0.72 to 1.04; P=0.12).

Despite subgroup analysis suggesting decreased death rates from cardiovascular causes in the latter group, there was no significant difference in the primary endpoint of death from any cause.

Bottom line: The addition of CABG to medical therapy for patients with CAD and left ventricular dysfunction does not decrease mortality.

Reference: Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616.

Linezolid Not Superior to Glycopeptide Antibiotics in Treatment of Nosocomial Pneumonia

Clinical question: Is linezolid superior to glycopeptide antibiotics in the treatment of nosocomial pneumonia?

Background: Current ATS/IDSA guidelines suggest that linezolid might be preferred over glycopeptide antibiotics (i.e. vancomycin and teicoplanin) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although this recommendation is based on a retrospective subgroup analysis of one randomized trial. No systematic reviews have looked at the comparative efficacy and safety of linezolid and glycopeptide antibiotics for nosocomial pneumonia.

Study design: Meta-analysis using a highly sensitive search method.

Setting: Eight multicenter, randomized controlled trials (RCTs).

Synopsis: The study authors retrieved 762 articles with a highly sensitive search strategy, from which eight RCTs were identified that met study criteria for a total of 1,641 patients. Primary outcome of clinical success at test-of-cure was not different between the two classes of antibiotics (pooled RR 1.04, 95% CI 0.97-1.11, P=0.28). Other endpoints, including mortality and microbiologic eradication, were similar between the two groups.

Clinical success in the subgroup of patients with culture-confirmed MRSA pneumonia was not different than those without culture-proven MRSA, although the study was not powered for subgroup analysis. Risk of thrombocytopenia and renal impairment were not statistically different in the limited subgroup of trials reporting this data.

The results should not be generalized to community-acquired MRSA or MRSA pneumonia with characteristics of PVL toxin-producing strain.

Bottom line: For the treatment of nosocomial pneumonia, there was no significant difference in clinical success or mortality between linezolid and glycopeptide antibiotics.

Citation: Walkey AJ, O’Donnell MR, Weiner RS. Linezolid vs. glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2011;139: 1148-1155.

CRP and Procalcitonin Independently Differentiated Pneumonia from Asthma or COPD Exacerbation

Clinical question: Are biomarkers such as CRP or procalcitonin useful in differentiating pneumonia from asthma or COPD exacerbation in hospitalized patients?

Background: Antibiotic overuse is associated with the emergence of drug resistance. One potential strategy to decrease antibiotic overuse is biomarker-guided therapy. Several randomized controlled trials (RCT) with procalcitonin-guided therapy have resulted in reduced antibiotic use for symptoms of acute respiratory tract infections (RTI). The use of CRP as a biomarker in acute RTI is not as well-described.

Study design: Prospective, observational, diagnostic accuracy study.

Setting: Winter months, 2006 to 2008, in two hospitals in England.

Synopsis: The study examined 319 patients: 62 with pneumonia, 96 with asthma exacerbation, and 161 with COPD exacerbation. Patients with pneumonia had significantly higher procalcitonin and CRP levels than those with COPD (P<0.0001) or asthma (P<0.0001). The area under receiver operator characteristic curve for distinguishing between pneumonia (requiring antibiotics) and asthma exacerbation (not requiring antibiotics) was 0.93 (0.88-0.98) for procalcitonin and 0.96 (0.93-1.00) for CRP. A CRP value >48 mg/L had a sensitivity of 91% (95% CI 80%-97%) and specificity of 93% (95% CI 86-98).

Using this CRP threshold, antibiotic use would have been reduced by 88% in asthma exacerbation, 76% in COPD exacerbation, and 9% in pneumonia cases.

This strategy was developed in a single-center study and requires further validation in a multicenter RCT.

Bottom line: Procalcitonin and CRP were elevated in patients with pneumonia compared to patients with asthma or COPD exacerbation and might be useful in guiding antibiotic usage.

Citation: Bafadhel, M, Clark TW, Reid, C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011;139:1410-1418.

Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer

Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?

Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).

Study design: Multicenter, randomized, controlled Phase 2-3 trial.

Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.

Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).

Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.

Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.

Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.

Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.

MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections

Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?

Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.

Study design: Quality-improvement (QI) observational initiative.

Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.

Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).

It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.

Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.

Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.

New Left Bundle Branch Block Does Not Predict MI

Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?

Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.

Study design: Prospective cohort study.

Setting: University hospital in the U.S.

Synopsis: From 1994 to 2009, 401 consecutive patients undergoing evaluation for acute coronary syndrome with LBBB on initial ECG were included in the analysis. Of these patients, 64% had new (37%) or presumably new (27%) LBBB. Twenty-nine percent were diagnosed with MI, but there was no difference in frequency or size of MI between the new, presumably new, or chronic LBBB groups.

Concordant ST-T changes were an independent predictor of MI (OR 17, 95% CI 3.4-81, P<0.001) and mortality (OR 4.3, 95% CI 1.3-15, P<0.001), although this finding was present in only about 11% of the patient group.

Bottom line: Left bundle branch block is not a predictor of MI, although concordant ST-T changes were an independent predictor of MI and mortality.

Citation: Kontos MC, Aziz HA, Chau VQ, et al. Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction. Am Heart J. 2011;161(4):698-704.

Acute Beta-Blocker Therapy for MI Increased Risk of Shock

Clinical question: How does acute beta-blocker therapy in myocardial infarction (MI) impact outcome?

Background: Long-term treatment with beta-blockers after myocardial infarction (MI) reduces mortality. However, data regarding outcome after acute use of beta-blockers in the first 24 hours of MI is conflicting. Updated ACA/AHA guidelines for STEMI and NSTEMI recommend caution when using beta-blockers in the first 24 hours, particularly in patients at risk for shock.

Study design: Observational registry study.

Setting: Two hundred ninety-one U.S hospitals.

Synopsis: More than 34,600 patients diagnosed with STEMI and NSTEMI from January 2007 to June 2008 were identified from a national QI MI registry. Patients were stratified by guideline-stated risk factors for shock; age >70, HR >110, and systolic BP <120 were associated with increased risk of composite outcome of shock or death.

At least one high-risk factor was present in 63% of the NSTEMI patients and 45% of STEMI patients; however, >90% of these patients received acute beta-blocker therapy. Nearly half (49%) of the NSTEMI patients received beta-blockers in the ED and 62% of the STEMI patients received beta-blockers before PCI.

In a multivariable model, NSTEMI patients receiving beta-blocker therapy in the ED were more likely to develop cardiogenic shock (OR 1.54, 95% CI 1.26-1.88, P<.001), as were STEMI patients receiving beta-blocker therapy prior to PCI (1.40, 95% CI 1.10-1.79, P=.006).

Bottom line: Caution should be exercised when using beta-blocker therapy during acute MI, particularly in the ED or prior to primary PCI.

Citation: Kontos MC, Diercks DB, Ho MP, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J. 2011;161(5):864-870.

Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

For more physician reviews of HM-related literature, visit our website.

Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

For more physician reviews of HM-related literature, visit our website.

Clinical question: Is transcatheter aortic-valve replacement comparable to surgical valve replacement in high-operative-risk patients?

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, patients who were not surgical candidates underwent transcatheter aortic-valve replacement, resulting in reduced symptoms and 20% improvement in one-year survival rates. Transcatheter valve replacement has not been compared to surgical replacement in high-operative-risk patients who remain candidates for surgical replacement.

Study design: Randomized controlled trial powered for noninferiority.

Setting: Twenty-five centers in the U.S., Canada, and Germany.

Synopsis: Six-hundred ninety-nine high-operative-risk patients with severe aortic stenosis were randomized to undergo transcatheter aortic-valve replacement or surgical replacement. In the intention-to-treat analysis, all-cause mortality rates were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% vs. 26.8% at one year (P=0.44). Rates of major stroke were 3.8% in the transcatheter group compared with 2.1% in the surgical group at 30 days (P=0.20) and 5.1% vs. 2.4% at one year (P=0.07).

The transcatheter group had a significantly higher rate of major vascular complications, but had lower rates of major bleeding and new onset-atrial fibrillation. At one year, improvement in cardiac symptoms and the six-minute-walk distance were not significantly different in the two groups.

Bottom line: In high-operative-risk patients with severe aortic stenosis, transcatheter and surgical aortic-valve replacement had similar mortality at 30 days and one year, but there were a few significant differences in periprocedural risks.

Citation: Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.

For more physician reviews of HM-related literature, visit our website.