Therapeutics
Review: -blockers do not reduce mortality in myocardial infarction in the reperfusion era Clinical impact ratings:
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Bangalore S, Makani H, Radford M, et al. Clinical outcomes with beta-blockers for myocardial infarction: a meta-analysis of randomized trials. Am J Med. 2014;127:939-53.
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Question In patients with myocardial infarction (MI), do -blockers reduce mortality?
Review scope Included studies compared -blockers with control (other active treatment, no treatment, or placebo) in patients with MI. Studies that compared -blockers with other -blockers or investigated post-MI heart failure/left ventricular (LV) systolic dysfunction were excluded. Outcomes were all-cause mortality, cardiovascular (CV) mortality, sudden death, recurrent MI, angina pectoris, heart failure, cardiogenic shock, stroke, and drug discontinuation.
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, and Google Scholar were searched to Feb 2013 for randomized controlled trials (RCTs) with ≥ 100 patients. 60 RCTs (n = 102 003), ranging in size from 100 to 45 852 patients, met the selection criteria. 48 RCTS (n = 31 479) were from the pre–reperfusion era, and 12 (n = 48 806) were from the reperfusion era. 40 RCTs assessed patients with acute MI (randomized ≤ 48 h after symptom onset), and 20 assessed post-MI patients (randomized > 48 h after symptom onset). Follow-up ranged from in-hospital to 4 years (mean 10 mo).
Main results Pre−reperfusion era trials. In acute MI, -blockers reduced allcause mortality (relative risk [RR] 0.86, 95% CI 0.79 to 0.94), CV mortality (RR 0.87, CI 0.78 to 0.98), MI (RR 0.78, CI 0.62 to 0.97), and angina (RR 0.88, CI 0.82 to 0.95) and increased study drug discontinuation (RR 1.13, CI 1.02 to 1.24) compared with control. Groups did not differ for sudden death, heart failure, cardiogenic shock, or stroke. In post-MI trials, -blockers reduced mortality (RR 0.79, CI 0.71 to 0.86) and recurrent MI (RR 0.77, CI 0.69 to 0.87) and increased risk for heart failure (RR 1.16, CI 1.04 to 1.30) and study drug discontinuation (RR 1.11, CI 1.04 to 1.17). Reperfusion era trials. In acute MI, -blockers reduced recurrent MI and angina and increased heart failure, cardiogenic shock, and study drug discontinuation compared with control (Table). Groups did not differ for all-cause mortality (Table), CV mortality, sudden death, or stroke. In post-MI trials, -blockers increased risk for heart failure (RR 3.77, 95% CI 1.59 to 8.94) and
多多多多多多夞 study drug discontinuation (RR 1.49, CI 1.01 to 2.19) compared with control; groups did not differ for mortality or recurrent MI.
Conclusion In patients with myocardial infarction, -blockers do not reduce mortality in the reperfusion era. Source of funding: No external funding. For correspondence: Dr. S. Bangalore, New York University School of Medicine, New York, NY, USA. E-mail [email protected].
Commentary The review by Bangalore and colleagues provides important information on the declining value of -blockers in the reperfusion era. The conclusions are solid and should influence future clinical guidelines that are the basis for quality-of-care indicators. Oral -blocker therapy initiated within 24 hours unless contraindicated is currently a class I indicated treatment for ST-elevation MI (STEMI) but, as noted in the review, is a potential precipitant of heart failure and shock. Therefore, initial doses should be low and dose titration cautious. Literature from the reperfusion era (thrombolytic and primary percutaneous coronary intervention) and the prereperfusion era differ in several important ways. There is a tendency for lowerrisk patients to be represented in reperfusion era trials because reperfusion patients are known to be at lower risk than patients not selected for reperfusion therapy. Further, trial patients tend to be at lower risk than patients not selected for trial enrollment. Lastly, successful reperfusion reduces risk to such an extent that the benefit of -blockade is probably diminished. The large COMMIT trial (1), which dominates the reperfusion population in the review, was done primarily in China. The patient population in this and other trials done in Eastern Europe may not be comparable to western populations despite identical research protocols. Finally, early IV followed by oral -blockers for STEMI is more likely to cause harm than oral -blockers started within 24 hours of hospitalization (1).
The findings of this meta-analysis should challenge the clinical guideline recommendation for routine administration of -blockers as mandatory STEMI treatment. -blockers are most beneficial in nonreperfused patients and in reperfused patients with LV dysfunction or mild heart failure, in whom -blockers should be -blockers vs control in acute myocardial infarction in the reperfusion era* initiated with caution, with close monitoring for Outcomes Number of Weighted event rates At a mean 10 mo signs of decompensation. trials (n)
-blockers
Control
RRR (95% CI)
NNT (CI)†
All-cause mortality
10 (48 806)
7.4%
7.6%
2% (⫺5 to 8)
Not significant
Recurrent myocardial infarction
8 (48 274)
1.2%
1.7%
28% (17 to 38)
209 (154 to 344)
6 (2157)
16%
19%
20% (2 to 35)
26 (15 to 258)
Angina
RRI (CI)
NNH (CI)†
Heart failure
9 (47 372)
14%
13%
10% (5 to 16)
79 (50 to 158)
Cardiogenic shock
4 (46 437)
5.0%
3.9%
29% (18 to 40)
90 (65 to 145)
Drug discontinuation
3 (46 124)
14%
8.4%
64% (55 to 73)
19 (17 to 22)
*Abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from control event rates and relative risks in article.
Steven Borzak, MD University of Miami Miller School of Medicine Charles E. Schmidt College of Medicine Florida Atlantic University Atlantis, Florida, USA Reference 1. Chen ZM, Pan HC, Chen YP, et al; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005; 366:1622-32.
†CIs calculated from control event rates and relative risks in article; for drug discontinuation, both NNH and CI were calculated from data in article.
17 March 2015
Annals of Internal Medicine
ACP Journal Club
JC3
姝 2015 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/933569/ by a University of Pittsburgh User on 05/07/2017
Review: -blockers do not reduce mortality in myocardial infarction in the reperfusion era Clinical impact ratings:
多多多多多多夞
多多多多多多夞
Bangalore S, Makani H, Radford M, et al. Clinical outcomes with beta-blockers for myocardial infarction: a meta-analysis of randomized trials. Am J Med. 2014;127:939-53.
多多多多多多多
Question In patients with myocardial infarction (MI), do -blockers reduce mortality?
Review scope Included studies compared -blockers with control (other active treatment, no treatment, or placebo) in patients with MI. Studies that compared -blockers with other -blockers or investigated post-MI heart failure/left ventricular (LV) systolic dysfunction were excluded. Outcomes were all-cause mortality, cardiovascular (CV) mortality, sudden death, recurrent MI, angina pectoris, heart failure, cardiogenic shock, stroke, and drug discontinuation.
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, and Google Scholar were searched to Feb 2013 for randomized controlled trials (RCTs) with ≥ 100 patients. 60 RCTs (n = 102 003), ranging in size from 100 to 45 852 patients, met the selection criteria. 48 RCTS (n = 31 479) were from the pre–reperfusion era, and 12 (n = 48 806) were from the reperfusion era. 40 RCTs assessed patients with acute MI (randomized ≤ 48 h after symptom onset), and 20 assessed post-MI patients (randomized > 48 h after symptom onset). Follow-up ranged from in-hospital to 4 years (mean 10 mo).
Main results Pre−reperfusion era trials. In acute MI, -blockers reduced allcause mortality (relative risk [RR] 0.86, 95% CI 0.79 to 0.94), CV mortality (RR 0.87, CI 0.78 to 0.98), MI (RR 0.78, CI 0.62 to 0.97), and angina (RR 0.88, CI 0.82 to 0.95) and increased study drug discontinuation (RR 1.13, CI 1.02 to 1.24) compared with control. Groups did not differ for sudden death, heart failure, cardiogenic shock, or stroke. In post-MI trials, -blockers reduced mortality (RR 0.79, CI 0.71 to 0.86) and recurrent MI (RR 0.77, CI 0.69 to 0.87) and increased risk for heart failure (RR 1.16, CI 1.04 to 1.30) and study drug discontinuation (RR 1.11, CI 1.04 to 1.17). Reperfusion era trials. In acute MI, -blockers reduced recurrent MI and angina and increased heart failure, cardiogenic shock, and study drug discontinuation compared with control (Table). Groups did not differ for all-cause mortality (Table), CV mortality, sudden death, or stroke. In post-MI trials, -blockers increased risk for heart failure (RR 3.77, 95% CI 1.59 to 8.94) and
多多多多多多夞 study drug discontinuation (RR 1.49, CI 1.01 to 2.19) compared with control; groups did not differ for mortality or recurrent MI.
Conclusion In patients with myocardial infarction, -blockers do not reduce mortality in the reperfusion era. Source of funding: No external funding. For correspondence: Dr. S. Bangalore, New York University School of Medicine, New York, NY, USA. E-mail [email protected].
Commentary The review by Bangalore and colleagues provides important information on the declining value of -blockers in the reperfusion era. The conclusions are solid and should influence future clinical guidelines that are the basis for quality-of-care indicators. Oral -blocker therapy initiated within 24 hours unless contraindicated is currently a class I indicated treatment for ST-elevation MI (STEMI) but, as noted in the review, is a potential precipitant of heart failure and shock. Therefore, initial doses should be low and dose titration cautious. Literature from the reperfusion era (thrombolytic and primary percutaneous coronary intervention) and the prereperfusion era differ in several important ways. There is a tendency for lowerrisk patients to be represented in reperfusion era trials because reperfusion patients are known to be at lower risk than patients not selected for reperfusion therapy. Further, trial patients tend to be at lower risk than patients not selected for trial enrollment. Lastly, successful reperfusion reduces risk to such an extent that the benefit of -blockade is probably diminished. The large COMMIT trial (1), which dominates the reperfusion population in the review, was done primarily in China. The patient population in this and other trials done in Eastern Europe may not be comparable to western populations despite identical research protocols. Finally, early IV followed by oral -blockers for STEMI is more likely to cause harm than oral -blockers started within 24 hours of hospitalization (1).
The findings of this meta-analysis should challenge the clinical guideline recommendation for routine administration of -blockers as mandatory STEMI treatment. -blockers are most beneficial in nonreperfused patients and in reperfused patients with LV dysfunction or mild heart failure, in whom -blockers should be -blockers vs control in acute myocardial infarction in the reperfusion era* initiated with caution, with close monitoring for Outcomes Number of Weighted event rates At a mean 10 mo signs of decompensation. trials (n)
-blockers
Control
RRR (95% CI)
NNT (CI)†
All-cause mortality
10 (48 806)
7.4%
7.6%
2% (⫺5 to 8)
Not significant
Recurrent myocardial infarction
8 (48 274)
1.2%
1.7%
28% (17 to 38)
209 (154 to 344)
6 (2157)
16%
19%
20% (2 to 35)
26 (15 to 258)
Angina
RRI (CI)
NNH (CI)†
Heart failure
9 (47 372)
14%
13%
10% (5 to 16)
79 (50 to 158)
Cardiogenic shock
4 (46 437)
5.0%
3.9%
29% (18 to 40)
90 (65 to 145)
Drug discontinuation
3 (46 124)
14%
8.4%
64% (55 to 73)
19 (17 to 22)
*Abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from control event rates and relative risks in article.
Steven Borzak, MD University of Miami Miller School of Medicine Charles E. Schmidt College of Medicine Florida Atlantic University Atlantis, Florida, USA Reference 1. Chen ZM, Pan HC, Chen YP, et al; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005; 366:1622-32.
†CIs calculated from control event rates and relative risks in article; for drug discontinuation, both NNH and CI were calculated from data in article.
17 March 2015
Annals of Internal Medicine
ACP Journal Club
JC3
姝 2015 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/933569/ by a University of Pittsburgh User on 05/07/2017
