Ximelagatran vs Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

Abstract

ONVALVULAR ATRIAL FIBRILlation is implicated in nearly 15% of strokes. 1 By metaanalysis of 6 randomized trials, dose-adjusted warfarin decreases stroke risk by 62%. 2,3 In practice, the risk of bleeding limits treatment with warfarin, particularly among the elderly. Variability of anticoagulation intensity from interactions with foods and medication 4 necessitates frequent monitoring and dose adjustments yet leaves patients outside the therapeutic range almost half the time. 5,6 Underuse of warfarin in patients with atrial fibrillation at high risk of bleeding 5,6 calls for safer, more dependable alternatives. 7,8 The direct thrombin inhibitor ximelagatran offers fixed oral dosing without need for coagulation monitoring, rapid onset and offset of action, stable pharmacokinetics with little potential for drug interactions, and no known food interactions. 9-12 The SPORTIF (Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation) program included 2 longterm trials comparing ximelagatran to warfarin for prevention of thromboembolism in patients with atrial fibrillation. The open-label SPORTIF III study See also pp 681, 699, and 736. *Authors/SPORTIF Executive Steering Committee and the SPORTIF V investigators are listed at the end of this article.

Atrial Fibrillation and Antithrombotic Therapy in a 75-Year-Old Population

“…Again, this may be a local phenomenon, but may also reflect a high focus on the importance of anticoagulant therapy in AF in Norway. In this study, where most patients had their VKA treatment monitored by general practitioners, the proportion of patients within the therapeutic INR range was high, about 65%, comparable to the results from recent well-conducted clinical studies [25, 26]. …”

Factors Associated With Major Bleeding Events

“…Although ROCKET AF patients were at increased risk for both stroke (e.g., 55% with prior stroke, TIA, or systemic embolism and a median CHADS 2 ) risk score of 3 and bleeding (e.g., median age 73 years, 91% with hypertension), the major bleeding rates were similar to those in recent studies (14–18). However, cross-trial comparisons are challenging, because the patient populations and associated risk factors for stroke and bleeding, definitions of bleeding, and newer anticoagulants were clearly different in these trials.…”

Newer Anticoagulants for Non-Valvular Atrial Fibrillation

“…In addition, the most common adverse side effect of dabigatran was dyspepsia, and the authors believed that this was also related to the acid content of the tablets. Unlike in the previous trials evaluating ximelagatran, another oral direct thrombin inhibitor, rates of hepatotoxicity were not increased in the dabigatran groups compared to the warfarin group [22,23,24]. …”