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Antithrombotic Treatment and the Incidence of Angina Pectoris
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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