Diener Hans-Christoph
Department of Neurology, University of Essen, Hufelandstrasse 55, DE-45122 Essen, Germany.
Cerebrovasc Dis. 2006;21(4):279-93. doi: 10.1159/000091265. Epub 2006 Jan 5.
To show results of a prespecified pooled analysis of the studies SPORTIF III (open-label) and SPORTIF V (double-blind), to assess the homogeneity of the results and to explore subgroup analyses and adverse events.
7,329 patients with atrial fibrillation (AF) and >or=1 additional stroke risk factor were randomized to warfarin (international normalized ratio 2.0-3.0) or ximelagatran (36 mg twice daily). Over 11,346 patient-years (mean 18.5 months/patient), 184 patients developed primary events of stroke and systemic embolism (ximelagatran 1.62 vs. warfarin 1.65%/year; p = 0.94). Heterogeneity between trials with respect to the primary event rate (study-by-treatment interaction p = 0.026) was found. This could not be explained statistically by baseline patient characteristics or by treatment (except perhaps by the better anticoagulation with warfarin in SPORTIF V) and was not evident for secondary end-points. There was no conclusive difference in major bleeding rates (ximelagatran 1.88 vs. warfarin 2.46%/year; p = 0.054), but combined minor plus major bleeding was lower with ximelagatran (31.7 vs. 38.7%/year; p < 0.0001). Elevation of liver enzymes occurred more frequently in patients taking ximelagatran (6.1% vs. warfarin 0.8%; p < 0.0001) and was reversible except in rare cases.
Fixed-dose oral ximelagatran without coagulation monitoring prevented stroke and systemic embolism as effectively as warfarin in patients with AF. Differences in the results of the two trials might relate to consistency of warfarin anticoagulation, different degree of blinding in the two trials, other concomitant therapies or chance. Further investigation is required to explore the long-term safety profile of ximelagatran.
展示对SPORTIF III（开放标签）和SPORTIF V（双盲）研究进行预先指定的汇总分析结果，评估结果的同质性，并探索亚组分析和不良事件。
7329例患有房颤（AF）且至少有一项额外卒中危险因素的患者被随机分为华法林组（国际标准化比值2.0 - 3.0）或希美加群组（每日两次，每次36 mg）。在超过11346患者年（平均每位患者18.5个月）期间，184例患者发生了卒中及全身性栓塞的主要事件（希美加群1.62%/年，华法林1.65%/年；p = 0.94）。发现试验间在主要事件发生率方面存在异质性（研究与治疗交互作用p = 0.026）。这无法通过基线患者特征或治疗在统计学上得到解释（也许除了SPORTIF V中华法林更好的抗凝效果），并且在次要终点方面不明显。主要出血率无确凿差异（希美加群1.88%/年，华法林2.46%/年；p = 0.054），但希美加群的轻微加主要出血合并发生率较低（31.7%/年对38.7%/年；p < 0.0001）。服用希美加群的患者肝酶升高更频繁（6.1%对华法林0.8%；p < 0.0001），除罕见情况外是可逆的。
无需凝血监测的固定剂量口服希美加群在预防房颤患者的卒中和全身性栓塞方面与华法林同样有效。两项试验结果的差异可能与华法林抗凝的一致性、两项试验不同程度的盲法、其他伴随治疗或机遇有关。需要进一步研究以探索希美加群的长期安全性。
