Thrombosis Prevention Trial - TPT
This randomized trial compared the effects of low-intensity anticoagulation with warfarin, low-dose aspirin, both, or neither on the primary prevention of fatal and nonfatal coronary events in "high-risk" British men.
The combination of aspirin and low-dose warfarin will be more effective in the primary prevention of coronary events than either agent alone.
Patients Screened: 61,422
Patients Enrolled: 5,085
Mean Follow Up: Median 6.8 years
Mean Patient Age: Mean 57 ± 7 years
Men aged 45-69 years from 108 medical group practices in the United Kingdom were screened. A novel risk score for coronary events was generated based on age, smoking history, family history, body mass index, blood pressure, total cholesterol, and fibrinogen levels. Men in the top 20% of the risk score distribution were considered high risk and therefore eligible for the study.
Current or recent history of possible peptic ulcer disease, history of possible or definite prior stroke or MI, or concurrent medication incompatible with trial medications
Fatal or nonfatal myocardial infarction (MI)
Thombotic and hemorrhagic stroke; bleeding
Patients were randomly assigned, in factorial fashion, to one of four groups:
1) Aspirin 75 mg daily plus warfarin placebo (A).
2) Aspirin placebo plus active warfarin (W).
3) Aspirin 75 mg daily plus warfarin placebo (WA).
4) Aspirin placebo plus warfarin placebo (P).
Patients assigned to active warfarin arms started at 2.5 mg daily and had their dose titrated to a target international normalized ratio of 1.5.
Warfarin containing regimens, compared with nonwarfarin containing regimens, were associated with a 21% relative reduction in total ischemic events (9.8 vs. 12.4 events/1,000 patient-years, p=0.02), primarily through a reduction in fatal events. Aspirin containing regimens, compared with nonaspirin containing regimens, were associated with a similar 20% relative reduction in ischemic events (9.5 vs. 11.8 events/1,000 patient-years, p=0.04), primarily through a reduction in nonfatal events. The only significant difference among the four individual study arms was between combined WA and P (8.7 vs. 13.3 events/1,000 patient-years, p=0.006).
No significant differences in stroke or death were observed between groups. The incidence of major bleeding events was similar in the three active therapy arms (0.6-0.9%, p=NS). "Intermediate" bleeding was more common in the WA group than W or A alone (6.3 vs. 4.0%, p<0.01).
Among men at high risk for coronary events, both low-dose aspirin and low-intensity warfarin were associated with efficacy in the primary prevention of coronary ischemic events. The combination of the two was associated with a nonsignificant trend toward fewer events than either alone, with no increase in major bleeding.
Main Trial Results
The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998;351:233-41.
Meade TW, Miller GJ. Combined use of aspirin and warfarin in primary prevention of ischemic heart disease in men at high risk. Am J Cardiol 1995;75:23B-26B.
Keywords: Stroke, Platelet Aggregation Inhibitors, Warfarin, Coronary Disease, Blood Pressure, Smoking, International Normalized Ratio, Cholesterol, Body Mass Index, Fibrinogen, Hemorrhage, Group Practice
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