Antiplatelet Therapy for Prevention of Death, Myocardial Infarction, and Stroke
Oral antiplatelet drugs are protective in most types of patients at increased risk of occlusive vascular events. Low-dose aspirin (75 to 150 mg daily) is an effective antiplatelet regimen for long-term use. Level of evidence: "A"A systematic review 1 including 197 trials comparing antiplatelet therapy with control, of which 195 provided vascular event data (135,640 patients), and 90 trials (77,000 patients) comparing different antiplatelet regimens, was abstracted in DARE.
Overall results on vascular events
- Overall, 7,705 (10.7%) vascular events were recorded among 71,912 on antiplatelet treatment versus 9,502 (13.2%) of 72,139 allocated controls (adjusted totals), (p<0.0001), a reduction of about one-quarter. These benefits were observed among all patient groups (previous MI, acute MI, previous stroke or transient ischaemic attack, acute stroke, other high risk). The absolute reductions in events were: 36 (standard error, SE=5) per 1,000 treated for two years among patients with previous MI; 38 (SE=5) per 1,000 patients treated for one month among those with acute MI; 36 (SE=6) per 1,000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (SE=3) per 1,000 treated for three weeks among those with acute stroke; and 22 (SE=3) per 1,000 treated for two years among other high-risk patients, with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (p=0.004), and atrial fibrillation (p=0.01). Although the benefit for acute stroke patients appeared smaller, this may reflect the shorter treatment period (less than one month) among acute stroke patients, compared with an average of 29 months for patients with a previous stroke or transient ischaemic attack.
- Overall, antiplatelets produced a proportional 34% reduction in nonfatal MI, a 26% reduction in nonfatal MI or death from coronary heart disease (p<0.0001), a 25% reduction in nonfatal strokes (p<0.0001), a 15% reduction in vascular deaths (p<0.0001), and a 26% reduction in the odds of fatal or nonfatal pulmonary embolism (p<0.01).
Risk of bleeding
- The proportional increase in risk of a major extracranial bleed with antiplatelet therapy was about 60% (odds ratio 1.6, 95% confidence interval, CI: 1.4, 1.8), with similar proportional increases in each of the 5 categories of patient.
Dose of aspirin
- There was no significant differences in reductions in vascular events between different aspirin regimens (e.g. less than 75 mg daily versus at least 75 mg daily), although doses of less than 75 mg have not been widely assessed. The evidence from trials of higher doses indicates that the proportional increase in risk of a major extracranial bleed was similar with daily aspirin dose of less than 325 mg but, since gastrotoxicity is known to be dose-dependent, a dose of 75 mg to 150 mg daily is appropriate for long term protection.
Effects of other antiplatelet drugs
- Indirect comparisons of different antiplatelets provided no clear evidence of differences in the effects on serious vascular events. Direct randomised comparisons suggested a possible reduction in risk with clopidogrel of 10% compared with aspirin, but the size of any additional benefit was statistically uncertain.
Effect of adding another antiplatelet drug to aspirin
- Among 10,404 patients in 25 trials comparing dipyridamole plus aspirin versus aspirin alone, the addition was associated with a non significant further 6% reduction in serious vascular events. Among 24,802 patients in 15 trials, the addition of an intravenous glycoprotein IIb/IIIa antagonist with aspirin alone produced a highly significant 19% proportional reduction in serious vascular events, preventing 20 events per 1,000 patients treated (p<0.0001). This reduction was larger among patients undergoing percutaneous coronary interventions (32%) than among patients not having such interventions (12%), (p<0.003), but the absolute benefit among patients with acute coronary syndromes was still significant. However, the benefits were offset by an increase in cranial bleeds (23 per 1,000 patients).
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References
- Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12;324(7329):71-86. [PubMed]