ASPIRIN AND
COUMADIN AFTER ACUTE CORONARY SYNDROMES (THE ASPECT-2 STUDY): A RANDOMISED
CONTROLLED TRIAL.
van Es RF, et al. Lancet 2002 Jul 13;360(9327):109-13.
BACKGROUND: Antiplatelet
treatment with aspirin and oral anticoagulants reduces recurrence 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.
COMMENT: The number needed to treat was 25 for one year, resulting in 1% less ischemic stroke, and 3% less “vascular death,” with a 10% drop out rate in the Coumadin group.