Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis

JAMA. 1999 Dec 1;282(21):2058-67. doi: 10.1001/jama.282.21.2058.


Context: Despite years of use in coronary artery disease (CAD) and several studies of its effectiveness, the role of oral anticoagulants (OAs) remains controversial.

Objective: To determine the effects of long-term OA therapy, stratified by the intensities of anticoagulation and aspirin therapy, on outcomes in patients with CAD.

Data sources: Studies were identified by MEDLINE, EMBASE, and CURRENT CONTENTS searches (1960-July 1999) and by reviewing reference lists and inquiring with experts and pharmaceutical companies.

Study selection: Studies were included if they were published between 1960 and July 1999, were randomized, had recruited patients with CAD, who had used OA therapy for at least 3 months. Of 43 articles identified, 30 articles (31 trials) were analyzed.

Data extraction: Information on type, duration, and method of monitoring OA therapy, as well as rates of death, myocardial infarction (MI), thromboembolic complications, stroke, and bleeding were abstracted by 2 independent observers.

Data synthesis: With high-intensity (international normalized ratio [INR], 2.8-4.8) OAs vs control (16 trials, 10056 patients), clear reductions in mortality (odds reduction [ORed], 22%; 95% confidence interval [CI], 13%-31%), MIs (ORed, 42%; 95% CI, 34%-48%), and thromboembolic complications including stroke (ORed, 63%; 95% CI, 53-71%) were observed, but were associated with a 6.0-fold (95% CI, 4.4- to 8.2-fold) increase in major bleeding. For moderate OAs (INR, 2-3) vs control (4 trials, 1365 patients) the ORed for death was 18% (95% CI, -6% to 37%); for MI, 52% (95% CI, 37%-64%); and for stroke, 53% (95% CI, 19%-73%), but it increased bleeding by 7.7-fold (95% CI, 3.3- to 18-fold). For moderate- to high-intensity OAs (INR, > or =2) vs aspirin (7 trials, 3457 patients), no reduction in death, MI, or stroke was observed, and it was associated with a 2.4-fold (95% CI, 1.6- to 3.6-fold) increase in major bleeding. For moderate- to high-intensity OAs and aspirin vs aspirin alone (3 trials, 480 patients), the ORed for death, MI, or stroke was 56% (95% CI, 17%-77%) and major bleeding increased by 1.9-fold (0.6- to 6.0-fold). For low-intensity OAs (INR, <2.0) and aspirin vs aspirin alone (3 trials, 8435 patients), no significant reduction in death, MI, or stroke was observed, and major bleeding increased by 1.3-fold (95% CI, 1.0- to 1.8-fold).

Conclusions: Among patients with CAD, high-intensity and moderate-intensity OA are effective in reducing MI and stroke but increase the risk of bleeding. In the presence of aspirin, low-intensity OA does not appear to be superior to aspirin alone, while moderate- to high-intensity OA and aspirin vs aspirin alone appears promising and the bleeding risk is modest, but this requires confirmation from ongoing trials.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use*
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Drug Therapy, Combination
  • Humans
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk
  • Stroke / epidemiology
  • Stroke / prevention & control


  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Aspirin