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| Oral anticoagulation best for preventing stroke during atrial fibrillation |
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08 June 2006
The oral anticoagulant warfarin is superior to dual antiplatelet therapy with clopidogrel plus aspirin in preventing vascular events in patients with atrial fibrillation, investigators report.
To assess the efficacy of both treatment regimens, Dr Stuart J. Connolly, of Hamilton Health Sciences Corporation, Hamilton, Ontario, and associates enrolled patients with atrial fibrillation and at least one other cardiovascular risk factor. Subjects were randomly assigned to clopidogrel 75 mg daily plus aspirin 75 to 100 mg daily (n=3,335). The remaining 3,371 were assigned to oral anticoagulant, primarily vitamin K antagonists dosed to keep the INR between 2.0 and 3.0.
The study was stopped early because of clear evidence of superiority of oral anticoagulant therapy: 164 primary outcome events (stroke, non CNS systemic embolus, MI or vascular death) in the anticoagulant group (annual risk 3.90%), versus 234 events in the other arm (annual risk 5.60%). The relative risk (RR) was 1.44, p=0.003). The greatest effect was on prevention of stroke (RR 1.72, p=0.001) and non-CNS systemic embolism (RR 4.66, p=0.005). The rates of major haemorrhage were similar between groups: RR 1.10, p=0.53), although clopidogrel plus aspirin was associated with significantly more minor bleeds (RR 1.23, p=0.0009).
These findings suggest that the adverse events are apparently caused by cardiac thrombus formation in patents with atrial fibrillation, for which oral anticoagulants are particularly effective.
In a related commentary, Dr Freek W. A. Verheugt, from University Medical Centre in Nijmegen, the Netherlands, writes that, whereas the benefit of aspirin plus clopidogrel outweighs the bleeding risk in trials of a year or less, "in longer-term aspirin plus clopidogrel studies this benefit is not seen." "At least in ischaemic heart disease, long-term oral anticoagulation is better than aspirin alone, whereas long-term aspirin plus clopidogrel is not and seems to have quite similar complications to oral anticoagulants."
Reference:
Lancet 2006; 367 (9526): 1903-1912.
Lancet 2006; 367 (9526): 1877-1878.
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