Preventing stroke in patients with atrial fibrillation: current treatments and new concepts.
Atrial fibrillation (AF) is common, and it increases the risk of stroke. Placebo-controlled trials consistently showed that warfarin reduces the risk of stroke by two thirds, and a meta-analysis of trials of aspirin show a one-fifth reduction. Meta-analysis of trials directly comparing warfarin and aspirin shows that warfarin reduces the risk of stroke compared with aspirin by about one third. Major advisory bodies recommend risk stratification of patients with AF and prophylactic therapy with warfarin for patients at higher risk. There are several problems with warfarin therapy, which have resulted in a widely documented underuse. These problems include a narrow therapeutic window, marked variability in pharmacokinetics, and contraindications. There are new promising approaches to stroke prevention in AF. One of these is combination antiplatelet therapy. In a large randomized trial, the combination of dipyridamole and aspirin has been shown to have additive benefits against stroke. The combination of clopidogrel and aspirin results in additive benefits against vascular events, with only a modest increase in bleeding. A trial of combined antiplatelet therapy in AF is warranted. Occlusion of the left atrial appendage, either with a transvenous device or with surgery, is another strategy that is being explored. A direct thrombin inhibitor, ximelagatran, has been shown to have an excellent pharmacokinetic profile and is being developed as an oral agent for stroke prevention in AF, and it will not need regular monitoring.
Connolly
Stuart J
SJ
Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. connostu@hhsc.ca
D001241:Aspirin / Q000627:therapeutic use; D020517:Atrial Appendage / Q000601:surgery; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D001384:Azetidines / Q000627:therapeutic use; D001596:Benzylamines; D000077144:Clopidogrel; D004176:Dipyridamole / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; C426686:ximelagatran; D014859:Warfarin; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin