Net Clinical Benefit of Adding Clopidogrel to Aspirin Therapy in Patients With Atrial Fibrillation for Whom Vitamin K Antagonists Are Unsuitable

Study Questions:

Does the addition of clopidogrel to aspirin provide net clinical benefit in patients with atrial fibrillation (AF)?


This was a post-hoc analysis of 10,041 patients with AF in the ACTIVE A and ACTIVE B trials in which a vitamin K antagonist (VKA), aspirin (75-100 mg/day), and aspirin plus clopidogrel (75 mg/day) were compared. The endpoints consisted of ischemic stroke, intracerebral hemorrhage, subdural hematoma, major extracranial hemorrhage, and myocardial infarction. These endpoints were weighted using three different weighting systems based on clinical impact. In one of the weighting systems, a weight of 1.5 was given to intracerebral hemorrhage or subdural hematoma, 1.0 to ischemic stroke, and 0 to extracranial hemorrhage or myocardial infarction. Net clinical benefit was calculated based on the incidence of each endpoint and the weighted sum of those rates in the treatment groups minus the weighted sum of endpoints in the placebo group.


With no weighting, adding clopidogrel to aspirin did not have significant net clinical benefit. With weighting, adding clopidogrel had significant net clinical benefit, with prevention of 0.57-0.67 ischemic stroke equivalents/100 patient-years.


The authors concluded that there is modest net clinical benefit of adding clopidogrel to aspirin in patients with AF in whom a VKA is not suitable.


In the ACTIVE A trial, adding clopidogrel to aspirin reduced the risk of stroke, but increased the risk for bleeding compared to aspirin alone. The weighted analysis used in this study accounts for the variable clinical importance of events that occur during follow-up, and indicates that there is net clinical benefit of the clopidogrel-aspirin combination compared to aspirin alone.

Clinical Topics: Vascular Medicine

Keywords: Hematoma, Subdural, Vitamin K, Stroke, Myocardial Infarction, Platelet Aggregation Inhibitors, Ticlopidine, Fibrinolytic Agents, Tetrazoles, Biphenyl Compounds, Hemorrhage, Cerebral Hemorrhage

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