Preventing stroke in atrial fibrillation: the SPORTIF programme.

Atrial fibrillation (AF) is the most common cardiac risk factor for stroke. Oral anticoagulants such as the vitamin K antagonist warfarin have been proven effective in reducing the risk of stroke in AF. Warfarin, however, has many disadvantages including the need for coagulation monitoring, a narrow therapeutic index, inter-/intra-patient variability and food-drug interactions. As a result, warfarin is underused in clinical practice and a viable alternative is needed. Ximelagatran, the first oral direct thrombin inhibitor, is given as a fixed dose, does not have a narrow therapeutic index, has low potential for drug interactions, has no significant food interactions and does not require coagulation monitoring. Ximelagatran has been evaluated in the Stroke Prevention using an ORal direct Thrombin Inhibitor in atrial Fibrillation (SPORTIF) trial programme, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials, SPORTIF III and V, compared ximelagatran (36 mg twice daily) with well-controlled warfarin (international normalized ratio 2.0-3.0) in a combined population of more than 7,000 moderate- to high-risk AF patients. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin at 21 months (1.6 vs. 2.3% per year, respectively; p = 0.10). Preliminary data from SPORTIF V appear to further support non-inferiority between the two agents. On-treatment analysis of the rate of major bleeding events shows an absolute, nonsignificant reduction in the event rate per year with ximelagatran versus warfarin in both studies. The results of SPORTIF III and V demonstrate that a fixed oral dose of ximelagatran, without coagulation monitoring, is comparable to dose-adjusted warfarin in preventing stroke and other thromboembolic complications among moderate- to high-risk AF patients and has a lower rate of both major and minor bleeding. With its positive benefit-risk ratio, ximelagatran may increase the population of eligible patients for anticoagulation with AF and maximize the potential of anticoagulation in the prevention of stroke.