Clopidogrel and aspirin versus aspirin alone for the prevention of stroke in patients with a history of atrial fibrillation: subgroup analysis of the CHARISMA randomized trial.
BACKGROUND
Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear.


METHODS
Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75-162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors.


RESULTS
Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49-2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6-1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7-2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone.


CONCLUSIONS
This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.
Hart
Robert G
RG
Department of Neurology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. hartr@uthscsa.edu
Bhatt
Deepak L
DL
Hacke
Werner
W
Fox
Keith A A
KA
Hankey
Graeme J
GJ
Berger
Peter B
PB
Hu
Tingfei
T
Topol
Eric J
EJ
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin