Atrial Fibrillation - Recent Key Trials on Anticoagulation

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Citation
US Cardiology, 2007;4(1):18-9

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Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is associated with a five-fold increase in the risk of stroke and embolism.1 Oral anticoagulation (OAC) with warfarin reduces stroke by two-thirds compared with no treatment.1–3 Compared with aspirin, OAC reduces the risk of stroke by 45% and reduces cardiovascular events by 29%.4 However, it increases the risk of major bleeding by about 70% compared with aspirin. In addition, the response to OAC is influenced by variations in hepatic function, gut flora, and interactions with numerous drugs and diet, requiring regular monitoring of the level of anticoagulation. Despite the fact that OAC is at present the treatment of choice for patients at higher risk of stroke,5 only about half of potentially eligible patients currently receive OAC.6 An effective, simple, and safe alternative to OAC could be of great potential clinical value.
Recently, new data in AF thromboprophylaxis for potential alternative approaches to anticoagulation have emerged from several large, randomized clinical trials. These studies have compared the efficacy of a new class of oral anticoagulants—the oral direct thrombin inhibitors—and that of the combination of two antiplatelet agents—aspirin plus clopidogrel—with standard warfarin therapy. This brief summary will review the results of these trials.

Trials with Direct Thrombin Inhibitors

Oral direct thrombin inhibitors are a new class of anticoagulants currently developed for stroke prevention in AF. Ximelagratan has been the first such compound that has been thoroughly evaluated in clinical trials. The compound has a predictable pharmacokinetic profile that is stable over time. With a rapid onset of action and metabolism independent of the hepatic cytochrome P450 enzyme system, ximelagratan has a low potential for drug interactions and no known food interactions, making coagulation monitoring and dose adjustments unnecessary. Two large pivotal trials have been carried out comparing the efficacy and safety of ximelagratan with that of warfarin. The Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III7 study was a European long-term phase III study, and similar to the North American SPORTIF V study.8 The major difference between the trials was that SPORTIF III was an open-label, randomized trial whereas anticoagulation was administered in a double-blind fashion in SPORTIF V.

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References
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