Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W).
OBJECTIVE
In ACTIVE-W, oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular events in patients with atrial fibrillation. However, because OAC carries important bleeding complications, risk stratification schemes have been devised to identify patients for whom the absolute benefits of OAC exceed its risks.


METHODS
Participants were risk-stratified with the widely-used CHADS(2) scheme. Treatment-specific rates of stroke and major bleeding were calculated for patients with a CHADS(2)=1 and compared to those with a CHADS(2)>1.


RESULTS
Observed stroke rates for those with a CHADS(2)=1 were 1.25% per year on C+A and 0.43% per year on OAC (RR=2.96, 95% CI: 1.26 to 6.98, P=0.01). Among patients with a CHADS(2)>1, the stroke rates were 3.15% per year on C+A and 2.01% per year on OAC (RR=1.58, 95% CI: 1.11 to 2.24, P=0.01) (P for interaction between stroke risk category and efficacy of OAC=0.19). The risk of major bleeding during OAC was significantly lower among patients with CHADS(2)=1 (1.36% per year) compared with CHADS(2)>1 (2.75% per year) (RR=0.49, 95% CI 0.30 to 0.79, P=0.003).


CONCLUSIONS
In this clinical trial, patients with a CHADS(2)=1 had a low risk of stroke, yet still derived a modest (<1% per year) but statistically significant absolute reduction in stroke with OAC and had low rates of major hemorrhage on OAC.
Healey
Jeff S
JS
Population Health Research Institute, McMaster University, 237 Barton St E, Hamilton, Ontario, Canada. healeyj@hhsc.ca
Hart
Robert G
RG
Pogue
Janice
J
Pfeffer
Marc A
MA
Hohnloser
Stefan H
SH
De Caterina
Raffaele
R
Flaker
Greg
G
Yusuf
Salim
S
Connolly
Stuart J
SJ
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D002985:Clinical Protocols; D000077144:Clopidogrel; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000925:Anticoagulants; D001713:Biphenyl Compounds; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014859:Warfarin; D000077144:Clopidogrel; D000077405:Irbesartan; D013988:Ticlopidine; D001241:Aspirin