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Christine Knottenbelt, MB, ChB; Patrick J. Brennan, MSc; Tom W. Meade, DM, FRS; for the Medical Research Council's General Practice Research Framework

Arch Intern Med. 2002;162:881-886.

Background  In primary prevention, anticoagulation with warfarin sodium to an international normalized ratio of 1.5 and 75 mg of aspirin per day each reduced the incidence of coronary heart disease (CHD). Effects on the development of angina pectoris and total CHD (resulting from angina, myocardial infarction, and coronary death) have been assessed, particularly in light of recent evidence that warfarin may have a "durable effect" on CHD through effects on the pathologic condition of the vessel walls involved.

Methods  The Thrombosis Prevention Trial was carried out in 5499 men aged 45 through 69 years who were at increased risk of CHD. The trial was factorial, with 1 group taking active warfarin and active aspirin, 1 taking active warfarin and placebo aspirin, 1 taking placebo warfarin and active aspirin, and 1 taking double placebo treatment. In addition to those with myocardial infarction and coronary death, men developing angina pectoris after entry to the trial were identified.

Results  Warfarin appeared to reduce the incidence of stable angina by 16% (95% confidence interval [CI], –14 to 38), although not significantly (P = .26), while aspirin increased the incidence by 39% (95% CI, 0 to 91) (P = .05). The incidence of stable angina was 37% (95% CI, –1 to 60) less in those taking warfarin than in those taking aspirin (P = .05). Warfarin reduced total CHD by 18% (95% CI, 4 to 30) (P = .01), while the reduction due to aspirin was 8% (95% CI, –10 to 22) (P = .36).

Conclusions  The results are compatible with the concept of a durable effect of warfarin on the chronic pathologic conditions underlying angina, although this has not been established with certainty. Further research is needed to confirm or refute our findings, because they carry potentially important implications for the primary prevention of CHD with the use of antithrombotic agents.

From the Medical Research Council's General Practice Research Framework, London, England. Dr Meade is now affiliated with the Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, University of London. A complete list of the participating general practices is published in Lancet (1998;351:240).

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