Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial

Background Antiplatelet treatment with aspirin and oral anticoagulants reduces reocurrence of ischaemic events after myocardial infarction. We aimed to investigate which of these drugs is more effective in the long term after acute coronary events, and whether the combination of aspirin and oral anticoagulants offers greater benefit than either of these agents alone, without excessive risk of bleeding. Methods In a randomised open-label trial in 53 sites, we randomly assigned 999 patients to low-dose aspirin, high-intensity oral anticoagulation, or combined low-dose aspirin and moderate intensity oral anticoagulation. Patients were followed up for a maximum of 26 months. The primary composite endpoint was first occurrence of myocardial infarction, stroke, or death. Findings The primary endpoint was reached in 31 (9%) of 336 patients on aspirin, in 17 (5%) of 325 on anticoagulants (hazard ratio 0•55 [95% CI 0•30–1•00], p=0•0479), and in 16 (5%) of 332 on combination therapy (0•50 [0•27–0•92], p=0•03). Major bleeding was recorded in three (1%) patients on aspirin, three (1%) on anticoagulants (1•03 [0•21–5•08], p=1•0), and seven (2%) on combination therapy (2•35 [0•61–9•10], p=0•2). Frequency of minor bleeding was 5%, 8% (1•68 [0•92–3•07], p=0•20), and 15% (3•13 [1•82–5•37], p=<0•0001), in the three groups, respectively. 164 patients permanently discontinued the study drug. Analyses were done by intention to treat. Interpretation In patients recently admitted with acute coronary events, treatment with high-intensity oral anticoagulants or aspirin with medium-intensity oral anticoagulants was more effective than aspirin on its own in reduction of subsequent cardiovascular events and death.