Record 1 of 1 - MEDLINE EXPRESS (R) 1996-1998

TI: 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. The Medical Research Council's General Practice Research Framework [see comments]

CM: Comment in: Lancet 1998 Jan 24;351(9098):227-8. Comment in: Lancet 1998 Apr 18;351(9110):1204; discussion 1206-7. Comment in: Lancet 1998 Apr 18;351(9110):1204-5; discussion 1206-7. Comment in: Lancet 1998 Apr 18;351(9110):1205; discussion 1206-7. Comment in: Lancet 1998 Apr 18;351(9110):1205-6; discussion 1206-7. Comment in: Lancet 1998 Apr 18;351(9110):1206; discussion 1206-7. Comment in: Lancet 1998 Apr 18;351(9110):1206-7. Comment in: ACP J Club 1998 Jul-Aug;129(1):4

SO: Lancet. 1998 Jan 24; 351(9098): 233-41

ISSN: 0140-6736

PY: 1998

LA: ENGLISH

CP: ENGLAND

AB: BACKGROUND: We aimed to evaluate low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease (IHD). METHODS: 5499 men aged between 45 years and 69 years at high risk of IHD were recruited from 108 practices in the UK that belong to the Medical Research Council's General Practice Research Framework. Initially, warfarin or placebo was randomly allocated to 1427 men; 1013 of these men later moved to a factorial stage of the trial, retaining their warfarin or placebo warfarin allocation and adding randomly allocated active or placebo aspirin. Another 4072 men entered directly into the factorial stage making a total of 5085 men. The four factorial treatment groups were: active warfarin and active aspirin (WA, n = 1277), active warfarin and placebo aspirin (W, n = 1268), and placebo warfarin and active aspirin (A, n = 1268), and placebo warfarin and placebo aspirin (P, n = 1272). The primary end-point was all IHD defined as the sum of coronary death and fatal and non-fatal myocardial infarction (MI). FINDINGS: The mean International Normalised Ratio (INR) of those on active warfarin was 1.47. The mean warfarin dose was 4.1 mg a day (range 0.5 mg-12.5 mg). There were 410 IHD events (142 fatal, 268 non-fatal). The main effect of warfarin (i.e., WA and W vs A and P) was a reduction in all IHD of 21% (95% CI 4-35, p = 0.02) chiefly due to a 39% reduction (15-57, p = 0.003) in fatal events so that warfarin reduced the death rate from all causes by 17% (1-30, p = 0.04). The main effect of aspirin (i.e., WA and A vs W and P) was a reduction in all IHD of 20% (1-35, p = 0.04) almost entirely due to a 32% reduction (12-48, p = 0.004) in non-fatal events. Absolute reductions in all

IHD due to warfarin or aspirin were 2.6 and 2.3 per 1000 person years, respectively. WA reduced all IHD by 34% (11-51, p = 0.006) compared with P. WA increased haemorrhagic and fatal strokes. Ruptured aortic or dissecting aneurysms occurred in 15 of those

who were or had been on warfarin compared with three of those who had not (p = 0.01). INTERPRETATION: These results add to evidence that aspirin reduces non-fatal IHD. Warfarin reduced all IHD chiefly because of an effect on fatal events. Combined treatment with warfarin and aspirin is more effective in the reduction of IHD than either agent on its own.

MESH: Administration,-Oral; Aged-; Anticoagulants-administration-and-dosage; Anticoagulants-adverse-effects; Aspirin-administration-and-dosage; Aspirin-adverse-effects; Cerebrovascular-Disorders-chemically-induced; Cerebrovascular-Disorders-epidemiology;

Double-Blind-Method; Drug-Therapy,-Combination; Factor-Analysis,-Statistical; Hemorrhage-chemically-induced; Incidence-; Middle-Age; Myocardial-Ischemia-mortality; Platelet-Aggregation-Inhibitors-administration-and-dosage; Platelet-Aggregation-Inhibitors-adverse-effects; Primary-Prevention; Risk-Factors; Warfarin-administration-and-dosage; Warfarin-adverse-effects

MESH: *Anticoagulants-therapeutic-use; *Aspirin-therapeutic-use; *Myocardial-Ischemia-prevention-and-control; *Platelet-Aggregation-Inhibitors-therapeutic-use; *Thrombosis-prevention-and-control; *Warfarin-therapeutic-use

TG: Comparative-Study; Human; Male; Support,-Non-U.S.-Gov't

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL

RN: 0; 0; 50-78-2; 81-81-2

NM: Anticoagulants; Platelet-Aggregation-Inhibitors; Aspirin; Warfarin

AN: 1998118275

UD: 199804

SB: AIM