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ARTICLE

Warfarin plus Aspirin after Myocardial Infarction or the Acute Coronary Syndrome: Meta-Analysis with Estimates of Risk and Benefit

Michael B. Rothberg, MD, MPH; Carmel Celestin, MD; Louis D. Fiore, MD, MPH; Elizabeth Lawler, MPH; and James R. Cook, MD, MPH

16 August 2005 | Volume 143 Issue 4 | Pages 241-250

Background: After the acute coronary syndrome, adding warfarin to standard aspirin therapy decreases myocardial infarction and stroke but increases major bleeding.

Purpose: To quantify the risks and benefits of warfarin therapy after the acute coronary syndrome.

Data Sources: MEDLINE from 1990 to October 2004. Additional data were obtained from study authors. Clinical risk factors were used to classify hypothetical patients into cardiovascular and bleeding risk groups on the basis of published data.

Study Selection: Randomized trials comparing intensive warfarin therapy (international normalized ratio > 2.0) plus aspirin with aspirin alone after the acute coronary syndrome.

Data Extraction: Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including myocardial infarction, stroke, revascularization, death, and major and minor bleeding. Rate ratios for outcomes were calculated and pooled by using the method of DerSimonian and Laird.

Data Synthesis: Ten trials involving a total of 5938 patients (11 334 patient-years) met the study criteria. Compared with aspirin alone, warfarin plus aspirin was associated with a decrease in the annual rate of myocardial infarction (0.022 vs. 0.041; rate ratio, 0.56 [95% CI, 0.46 to 0.69]), ischemic stroke (0.004 vs. 0.008; rate ratio, 0.46 [CI, 0.27 to 0.77]), and revascularization (0.115 vs. 0.135; rate ratio, 0.80 [CI, 0.67 to 0.95]). Warfarin was associated with an increase in major bleeding (0.015 vs. 0.006; rate ratio, 2.5 [CI, 1.7 to 3.7]). Mortality did not differ.

Limitations: Two large studies provided most of the data. Studies did not include coronary stenting, and results should not be applied to patients with stents. Relative risk reductions may not be consistent across risk groups.

Conclusions: For patients with the acute coronary syndrome who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding risks.

Editors' Notes Context Continued thrombin generation persists for several months after acute cardiac events. Contribution Data from 10 randomized trials involving 5938 patients with the acute coronary syndrome who were not stented showed that, compared with aspirin alone, warfarin plus aspirin decreased annual rates of myocardial infarction, ischemic stroke, and revascularization and increased major bleeding rates. In patients with low or average bleeding risks, numbers of cardiovascular events prevented by warfarin plus aspirin exceeded numbers of major bleeding episodes caused by it. Implications Benefits of warfarin plus aspirin may exceed harms in patients with the acute coronary syndrome who are not stented and do not have high bleeding risks. –The Editors

 

Author and Article Information

From Baystate Medical Center, Springfield, Massachusetts, and Tufts University School of Medicine, Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Michael B. Rothberg, MD, MPH, Division of General Medicine and Geriatrics, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199; e-mail, Michael.Rothberg{at}bhs.org.

Current Author Addresses: Dr. Rothberg: Division of General Medicine and Geriatrics, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199.

Dr. Celestin: Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199.

Dr. Fiore and Ms. Lawler: Massachusetts Veterans Epidemiology Research and Information Center, 150 South Huntington Avenue, Boston, MA 02130.

Dr. Cook: Cardiac Services, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199.

Author Contributions: Conception and design: M.B. Rothberg, C. Celestin.

Analysis and interpretation of the data: M.B. Rothberg, L.D. Fiore, E. Lawler, J.R. Cook.

Drafting of the article: M.B. Rothberg, J.R. Cook.

Critical revision of the article for important intellectual content: M.B. Rothberg, C. Celestin, L.D. Fiore, E. Lawler, J.R. Cook.

Final approval of the article: M.B. Rothberg, C. Celestin, L.D. Fiore, E. Lawler, J.R. Cook.

Provision of study materials or patients: L.D. Fiore, E. Lawler.

Statistical expertise: J.R. Cook.

Collection and assembly of data: M.B. Rothberg, C. Celestin, L.D. Fiore.

Related articles in Annals:

Summaries for Patients
Benefits and Harms of Warfarin plus Aspirin after Acute Coronary Events

Annals 2005 143: I-14. [Full Text]  

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