Lindh Jonatan D, Holm Lennart, Dahl Marja-Liisa, Alfredsson Lars, Rane Anders
Division of Clinical Pharmacology, C1-68, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
J Thromb Thrombolysis. 2008 Apr;25(2):151-9. doi: 10.1007/s11239-007-0048-2. Epub 2007 May 20.
Optimal warfarin prescription requires correct, individualized assessment of the warfarin-related bleeding risk, which randomised controlled trials may underestimate . Observational studies have reported a range of bleeding risks that differ 40-fold. This variation may be caused by time trends, variation in bleeding definition and study subject selection. We investigated the incidence of, and risk factors for severe bleeding in un-selected warfarin-treated patients from Sweden.
Between 2001 and 2005, 40 centres recruited warfarin-naïve patients commencing warfarin therapy and followed them prospectively with continuous registration of clinical data. The primary outcome was severe bleeding, according to the WHO universal definition of severe adverse drug reactions. The influence of potential risk factors was investigated by means of a Cox proportional-hazards model.
A total of 1523 patients contributed 1276 warfarin-exposed patient-years. The incidence of first-time severe bleeding was 2.3 per 100 patient-years (95% confidence interval 1.4 to 3.1). Male sex and use of drugs potentially interacting with warfarin were the only independent risk factors of severe bleeding, with hazard ratios of 2.8 and 2.3, respectively. Age, target International Normalized Ratio (INR), time spent outside target INR range, and warfarin dose requirement were not significantly associated with bleeding risk.
The risk of severe bleeding in a large naturalistic, prospective cohort of first-time warfarin users was lower than reported in some previous reports. Male gender was an independent predictor of severe bleeding as was the receipt of warfarin-interacting medications at the onset of anticoagulation therapy. Further studies are required to evaluate the effect these findings may have on the quality of current risk-benefit analysis involved in warfarin prescription.
华法林的最佳处方需要对华法林相关出血风险进行准确、个体化评估，而随机对照试验可能会低估这种风险。观察性研究报告的一系列出血风险相差40倍。这种差异可能由时间趋势、出血定义的差异以及研究对象的选择所致。我们调查了瑞典未选择的接受华法林治疗患者的严重出血发生率及危险因素。
2001年至2005年间，40个中心招募了开始接受华法林治疗的初治患者，并对他们进行前瞻性随访，持续记录临床数据。根据世界卫生组织对严重药物不良反应的通用定义，主要结局为严重出血。通过Cox比例风险模型研究潜在危险因素的影响。
共有1523例患者贡献了1276个华法林暴露患者年。首次严重出血的发生率为每100患者年2.3例（95%置信区间1.4至3.1）。男性以及使用可能与华法林相互作用的药物是严重出血仅有的独立危险因素，风险比分别为2.8和2.3。年龄、目标国际标准化比值（INR）、超出目标INR范围的时间以及华法林剂量需求与出血风险无显著相关性。
在一个大型的首次使用华法林的自然前瞻性队列中，严重出血风险低于一些既往报告中的情况。男性是严重出血的独立预测因素，抗凝治疗开始时接受与华法林相互作用的药物也是如此。需要进一步研究来评估这些发现可能对当前华法林处方中风险效益分析质量产生的影响。
