Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.
OBJECTIVE
This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.


BACKGROUND
Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.


METHODS
We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.


RESULTS
Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.


CONCLUSIONS
The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.
Cardiology Service, Hospital Clínico San Carlos, Prof. Martin lagos s/n, 28040 Madrid, Spain. fperezg.hcsc@salud.madrid.org
Francisco
F
Pérez-Gómez
Eduardo
E
Alegría
Jesus
J
Berjón
Jose A
JA
Iriarte
Javier
J
Zumalde
Antonio
A
Salvador
Luis
L
Mataix
D000074:Acenocoumarol / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D002423:Cause of Death; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004617:Embolism / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D019934:International Normalized Ratio; D020766:Intracranial Embolism / Q000401:mortality / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D008946:Mitral Valve Stenosis / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012459:Salicylates / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D000074:Acenocoumarol