Romanelli Robert J, Nolting Laura, Dolginsky Marina, Kym Eunice, Orrico Kathleen B
From the Palo Alto Medical Foundation Research Institute, Palo Alto, CA (R.J.R., L.N., M.D.); and Department of Clinical Pharmacy, University of California, San Francisco (E.K., K.B.O.).
Circ Cardiovasc Qual Outcomes. 2016 Mar;9(2):126-34. doi: 10.1161/CIRCOUTCOMES.115.002369. Epub 2016 Jan 26.
Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents.
A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10-2.14; P=0.020).
In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but-particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.
在非瓣膜性心房颤动治疗中，达比加群与华法林疗效及安全性对比的试验数据尚缺。我们试图回顾关于这些药物相对有效性及安全性的真实世界观察性证据。
从各数据库最早可用日期至2015年3月10日，对比较达比加群与华法林的纵向观察性研究进行系统检索。两名审阅者评估研究的合格性，并提取缺血性卒中、胃肠道及颅内出血的风险比。使用随机效应荟萃分析汇总风险比。进行Meta回归以评估治疗效应异质性。我们识别出232条独特的引文。七项回顾性队列研究符合研究合格标准，涉及348750例患者，平均随访2.2年。在汇总分析中，达比加群150mg在预防卒中方面不优于华法林（风险比，0.92；95%置信区间，0.84 - 1.01；P = 0.066），但颅内出血风险显著更低（0.44；0.34 - 0.59；P < 0.001）。达比加群150mg胃肠道出血风险显著高于华法林（1.23；1.01 - 1.50；P = 0.041），在老年与年轻人群研究中（年龄中位数/均值，≥75岁对<75岁；β = 1.53；95%置信区间，1.10 - 2.14；P = 0.020）这种差异更为明显。
在真实世界临床实践中，达比加群在预防非瓣膜性心房颤动患者缺血性卒中方面与华法林相当。然而，相对于华法林，达比加群颅内出血风险更低，但尤其是在老年人中，胃肠道出血风险更高。观察性研究的出血结局与关键的长期抗凝治疗随机评估试验结果一致。
