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Antiplatelet Trialist Group - Antiplatelet Trialist Group
Description:
Overview of 174 randomized trials of antiplatelet agents.
Hypothesis:
To determine the effects of prolonged antiplatelet therapy (one month or more) on vascular events in various categories of patients.
Study Design
Study Design:
Patients Screened: Not reported
Patients Enrolled: 102,459 (145 randomized trials with controls)
NYHA Class: Not reported.
Mean Follow Up: Variable
Mean Patient Age: Variable
Female: N/A
Mean Ejection Fraction: Not reported
Patient Populations:
Randomized trials that could have available for review by March 1990 of agents whose primary mode of action on the vascular system was thought to be thorugh inhibition of platelt aggregation or adhesion, or both. High-risk patients were considered those with known vascular disease or other condition(s) associated with increased risk of occlusive vascular disease.
Exclusions:
Agents known also to have a major vasodilating action (e.g. epoprostenol, oxpentifylline, ketanserin) or major anticoagulant action (e.g. heparin, warfarin).
Primary Endpoints:
Non fatal MI, non-fatal stroke, vascular deaths.
Drug/Procedures Used:
Patients were treated with a variety of antiplatelet therapies: cyclooxygenase inhibitors (e.g. aspirin, ibuprofen, naproxen), phosphodiesterase inhibitors (e.g. dipyridamole), agents with direct effects on platelet membranes (ticlopidine), thromboxane synthethase inhibitors, receptor blockers or both, phospholipase inhibitors, platelet calcium channel inhibitors.
Principal Findings:
This analysis compiled data on 145 randomized trials of antiplatelet agents versus control (~70,000 high-risk and ~30,000 low-risk patients) and 29 randomized trials comparing different agents (~10,000 high-risk patients). Among all high-risk patients, antiplatelet therapy was associated with reductions of ~1/3 in nonfatal MI, ~1/3 in nonfatal stroke, and ~1/6 in vascular death (all p < 0.00001). Specifically, among the ~20,000 acute MI patients, antiplatelet therapy was associated with 10% incidence of vascular events at 1 month compared to 14% for control subjects(p<0.00001). In the ~20,000 patients with prior MI, antiplatelet therapy was associated with 13% incidence of vascular events at 2 years vs 17% for control group (p<).00001). And among the ~10,000 patients with previous stroke or TIA, the 3 year incidence of vascular events was 18% for antiplatelet therapy vs 22% for controls (p<0.00001). Aspirin for secondary prevention was observed to confer a significant additional benefit when used between years 1 and 3, suggesting that indefinite treatment is most effective. The use of aspirin for primary prevention was associated with only a trend toward decreased vascular events (5-year benefit of ~4 per 1,000 patients treated, p = 0.09); of note, >99% of the data for this finding came from two seminal studies (British Doctors [BMJ 1988;296:313-6, US Physicians [N Engl J Med 1989;321:129-35)).
Interpretation:
Long-term antiplatelet therapy in patients at high risk of vascular disease offers significant protection against MI, stroke, and death. The agent with the most data and strongest benefit(s) was aspirin (75-325 mg/day). This analysis found no benefit of antiplatelet therapy for the primary prevention among low risk subjects.
References:
BMJ 1994;308:81–106.
Keywords: Phosphodiesterase Inhibitors, Stroke, Phospholipases, Thromboxanes, Cyclooxygenase Inhibitors, Platelet Aggregation Inhibitors, Ibuprofen, Coronary Disease, Ticlopidine, Calcium Channels, Naproxen, Cerebrovascular Disorders, Dipyridamole
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