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A Meta-analysis

Allison Oler, MD; Mary A. Whooley, MD; Jacqueline Oler, PhD; Deborah Grady, MD, MPH

JAMA. 1996;276(10):811-815.

Abstract
Objective.
—To estimate the risk of myocardial infarction (MI) and death in patients with unstable angina who are treated with aspirin plus heparin compared with patients treated with aspirin alone.

Data Sources.
—Studies were retrieved using MEDLINE, bibliographies, and consultation with experts.

Study Selection.
—Only published trials that enrolled patients with unstable angina, randomized participants to aspirin plus heparin vs aspirin alone, and reported incidence of myocardial infarction or death were included in the meta-analysis.

Data Extraction.
—Patient outcomes including MI or death, recurrent ischemic pain, and major bleeding during randomized treatment; revascularization procedures after randomization; and MI or death during the 2 to 12 weeks following randomization were extracted by 2 authors, 1 of whom was blinded to the journal, institution, and author of each study.

Data Synthesis.
—Six randomized trials were included. The overall summary relative risk (RR) of MI or death during randomized treatment was 0.67 (95% confidence interval [CI], 0.44-1.02) in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The summary RRs for secondary endpoints in patients treated with aspirin plus heparin compared with those treated with aspirin alone were 0.68 (95% CI, 0.40-1.17) for recurrent ischemic pain; 0.82 (95% CI, 0.56-1.20) for MI or death 2 to 12 weeks following randomization; 1.03 (95% CI, 0.74-1.43) for revascularization; and 1.99 (95% CI, 0.52-7.65) for major bleeding. We found no statistically significant heterogeneity among individual study findings.

Conclusions.
—Our findings are consistent with a 33% reduction in risk of MI or death in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The bulk of evidence suggests that most patients with unstable angina should be treated with both heparin and aspirin.

Author Affiliations
From the Departments of Medicine (Drs A. Oler, Whooley, and Grady) and Epidemiology and Biostatistics (Dr Grady), University of California, San Francisco, School of Medicine; the General Internal Medicine Section, San Francisco Veterans Affairs Medical Center (Drs Whooley and Grady); and the Department of Quantitative Methods, Drexel University, Philadelphia, Pa (Dr J. Oler).

Footnotes
Reprints: Deborah Grady, MD, MPH, General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, 111A1, 4150 Clement St, San Francisco, CA 94121.

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ABSTRACT | FULL TEXT  

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Collins et al.
NEJM 1997;336:847-860.
FULL TEXT  

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Journal Watch Cardiology 1996;1996:2-2.
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Collins and Peto
JAMA 1996;276:1873-1873.
ABSTRACT  

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Brophy and Blankfield
JAMA 1996;276:1873-1874.
ABSTRACT