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.

Predicting Bleeding Events in Anticoagulated Patients With Atrial Fibrillation: A Comparison Between the HAS‐BLED and GARFIELD‐AF Bleeding Scores

“…The original protocol and principal results have been previously described 14, 15, 16. In brief, the SPORTIF trials were 2 multicenter phase III clinical trials comparing the efficacy and safety of the direct thrombin inhibitor, ximelagatran, against warfarin in patients with nonvalvular AF.…”

Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review

“…Of these, 14 studies [50][51][52][53][54][55][56][57][58][59][60][61][62][63] (in 14 articles) reported data from observational designs, both prospective [50][51][52][53][54][55] and retrospective [56][57][58][59][60][61][62][63] in nature. The remaining four studies in 10 articles [64][65][66][67][68][69][70][71][72][73] were originally designed to assess the effectiveness of an anticoagulant without additional APT. However, these were included because they reported data on a subgroup of patients treated with combined anticoagulant plus APT.…”

“…[50][51][52][53][55][56][57][59][60][61][62][63][64][65] One RCT 39 and one non-randomised study 54 reported data on acenocoumarol (Sinthrome ® , Alliance) plus an APT compared with acenocoumarol alone. The remaining one RCT 41 reported data on fluindione plus aspirin compared with fluindione plus placebo.…”

“…The remaining one RCT 41 reported data on fluindione plus aspirin compared with fluindione plus placebo. 41 One study 72 reporting non-randomised comparisons used idraparinux, and one used dabigatran (Pradaxa ® , Boehringer Ingelheim) as anticoagulant agent, 73 whereas two studies 64,65 reported data on ximelagatran plus warfarin compared with ximelagatran alone. Doses of APT varied between studies.…”

“…The differences in the event rates reported by the included studies may reflect differences in the population risk profile, with some studies including high-risk AF populations (three RCTS 39,41,43 and seven nonrandomised comparisons 50,55,58,64,65,72,73 ) and/or intermediate-risk patients with AF (one RCT 39 ), whereas other studies did not report the risk profile of included patients (two RCTs 40,42 ) and 11 other nonrandomised comparisons. [51][52][53][54]56,57,[59][60][61][62][63] The sample size also varied considerably between included studies, from 43 participants in one RCT 40 to 118,606 in a large non-randomised comparison.…”