Cardiology · 1994
Antiplatelet Trialists' Collaboration Overview
Collaborative overview of randomised trials of antiplatelet therapy
By the early 1990s, dozens of randomized trials had tested aspirin and other antiplatelet agents in patients at risk for vascular events, but most were too small to yield reliable estimates of effect on mortality or stroke. The published literature was a patchwork: different patient populations, different doses, different endpoints, and different durations of follow-up. Clinicians reading individual trials could not extract a coherent message about which patients benefited, by how much, or at what risk. The question called for a different approach.
The Antiplatelet Trialists' Collaboration, coordinated from Oxford under Richard Peto and colleagues, assembled individual-patient data from 145 randomized trials covering roughly 100,000 patients at high vascular risk. The collaboration included trials of aspirin, dipyridamole, and other agents across patients with prior myocardial infarction, stroke or transient ischemic attack, unstable angina, and peripheral arterial disease. Pooling individual-patient data rather than published summary statistics gave the group statistical power no single trial could approach and allowed subgroup analyses that aggregate meta-analyses cannot perform reliably.
Antiplatelet therapy, predominantly aspirin at daily doses well below those used for analgesia, cut nonfatal myocardial infarction by about one-third, nonfatal stroke by a similar proportion, and vascular death by about one-sixth. Benefit was consistent across the different high-risk clinical categories; what varied was the absolute gain, which was naturally greatest where baseline risk was highest. Bleeding risk was real but, in the populations studied, was substantially outweighed by the cardiovascular benefit.
The BMJ published the overview in January 1994, and it became one of the most cited papers in cardiovascular medicine. Colin Baigent at the Oxford Clinical Trial Service Unit was among the key contributors to the collaborative's methodology. The overview's conclusions were direct enough to drive aspirin into secondary prevention guidelines for coronary disease, stroke, and peripheral arterial disease in virtually every country that had such guidelines.
Among its methodological contributions, the collaborative demonstrated that small, consistent effects across thousands of patients could be detected and quantified with precision, establishing individual-patient data meta-analysis as a legitimate and sometimes necessary alternative to single large trials. Later overviews in oncology, most notably the Early Breast Cancer Trialists' Collaborative Group analyses, followed the same model. Subsequent overviews from the same group clarified the dose-response relationship for aspirin and distinguished its role in primary prevention, where the benefit-to-bleeding ratio is considerably less favorable than in secondary prevention.
Key People
- Richard Peto — Oxford statistician who led the collaborative overview methodology
- Colin Baigent — Oxford clinical trialist, key contributor to the antiplatelet meta-analyses
- Antiplatelet Trialists' Collaboration — International group pooling data from 145 randomized trials
- Rory Collins — Oxford epidemiologist and co-director of the Clinical Trial Service Unit overseeing the work
BMJ 1994;308:81-106
Related landmarks
- 1994 · 4S (Scandinavian Simvastatin Survival Study) (Cardiology)
- 1995 · WOSCOPS (West of Scotland Coronary Prevention Study) (Cardiology)
- 1991 · SOLVD Treatment Trial (Cardiology)
- 1988 · ISIS-2 (Second International Study of Infarct Survival) (Cardiology)