ArticlesAspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial
Introduction
The beneficial effect of antithrombotic treatment in patients with acute coronary events suggests that prevention of thrombus formation after plaque rupture reduces subsequent cardiovascular events. Short-term use of aspirin and long-term use of oral anticoagulants are effective in patients who have had myocardial infarction.1, 2, 3 Compared with placebo, antiplatelet treatment, especially aspirin, reduces vascular events by 25% after myocardial infarction,1 and long-term treatment with coumadin reduced vascular events by 35%.2, 3 Indirect comparison of these trials suggests that coumadin could be more beneficial than aspirin. Aspirin has been compared directly with coumadin in patients who have had myocardial infarction, but only in two small clinical trials in the early 1980s,4, 5 in which no difference was recorded for reinfarction and mortality. Since then, lower doses of aspirin have been used, making combination treatment with anticoagulants more realistic than previously. At the start of our trial, aspirin with low-intensity coumadin (international normalised ratio [INR] values <1·5) was no more effective in prevention of ischaemic events in coronary artery disease than aspirin on its own.6 However, aspirin with moderate intensity coumadin (INR 2·0–3·0) was more effective than aspirin on its own.7
In the Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2) study, we assessed the effect of high-intensity coumadin and aspirin plus moderate-intensity coumadin, compared with aspirin on its own in patients who had had an acute coronary event.
Section snippets
Study design
The ASPECT-2 study was a prospective, multicentre, randomised, open-label trial. The study was done in accordance with the Declaration of Helsinki. The protocol was approved by the Netherlands National Health Insurance Council and by all local institutional ethics committees. All patients gave written informed consent.
Patients
Eligible patients were men or non-pregnant women who were admitted with acute myocardial infarction or unstable angina within the preceding 8 weeks. Myocardial infarction was
Results
In February, 1999, we stopped the study early because of slow patient recruitment. By that time, 999 patients had been enrolled in 53 hospitals across the Netherlands (figure 1). Five patients assigned to coumadin and one assigned to aspirin and coumadin were excluded because they refused to participate directly after randomisation, but before use of the study drug. Median length of follow-up was 12 months (range 0–26). The study drug was discontinued in 34 (10%) of 336 on aspirin, in 62 (19%)
Discussion
Plaque rupture and superimposed thrombus caused by platelet aggregation and activation of the coagulation cascade are major factors in the pathophysiology of acute coronary events. After the acute event, activation of anticoagulation is raised for several months,8 and this increase has been associated with increased risk of unfavourable outcome. In outpatients, a persistent effect can be achieved with oral anticoagulants.
In our study, high-intensity oral anticoagulation and the combination of
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