Schneeweiss Sebastian, Gopalakrishnan Chandrasekar, Bartels Dorothee B, Franklin Jessica M, Zint Kristina, Kulldorff Martin, Huybrechts Krista F
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (S.S., C.G., J.M.F., M.K., K.F.H.).
Global Epidemiology, Boehringer Ingelheim International GmbH, Ingelheim, Germany (D.B.B., K.Z.).
Circ Cardiovasc Qual Outcomes. 2019 Feb;12(2):e005173. doi: 10.1161/CIRCOUTCOMES.118.005173.
Background The increasing availability of electronic healthcare data enables ongoing monitoring of the effectiveness and safety of newly marketed medications. We sought to demonstrate a 5-year prospective monitoring system of dabigatran for stroke prevention that may expedite discovery and allow ongoing evidence development. Methods and Results Between 2011 and 2015, we conducted 9 sequential analyses of dabigatran versus warfarin users in a sequential cohort design in 2 US claims databases. Analyses 4 through 9 were prespecified, and analyses 1 through 3 were added subsequently using the same methodology. New users of anticoagulants with nonvalvular atrial fibrillation were followed until a study outcome of hospitalization for stroke (hemorrhagic and ischemic) or hospitalization for major hemorrhage (intracranial and extracranial). Hazard ratios and 95% CIs were estimated after 1:1 propensity score matching. Sequential analyses 1 through 3 on stroke prevention using data through June 2012 were limited by few events leading to wide CIs. As data accumulated the effect estimate in analysis 4 visually stabilized at a 25% risk reduction with increasingly narrower CIs (-46% to +9% in December 2012 and -42% to -2% in September 2015). Improved data-adaptive confounding adjustment with high-dimensional propensity score reached a stable state already at analysis 3 and was slightly closer to the randomized clinical trial finding (-39%). The risk of major hemorrhage was 28% lower in dabigatran initiators (-35% to -20%) a finding that was stable throughout analyses 2 to 9. Conclusions Prospectively monitoring the effectiveness and safety of dabigatran for stroke prevention allowed for early insights with increasing precision over time.
背景 电子医疗数据的可得性不断提高，使得对新上市药物的有效性和安全性进行持续监测成为可能。我们试图建立一个为期5年的达比加群预防卒中的前瞻性监测系统，该系统可能会加快发现速度并促进证据的持续积累。方法与结果 在2011年至2015年期间，我们在美国的2个索赔数据库中采用序贯队列设计对达比加群使用者与华法林使用者进行了9次序贯分析。分析4至9是预先设定的，分析1至3随后采用相同方法添加。对非瓣膜性心房颤动的抗凝剂新使用者进行随访，直至出现卒中住院（出血性和缺血性）或大出血住院（颅内和颅外）的研究结局。在1:1倾向评分匹配后估计风险比和95%可信区间。使用截至2012年6月的数据进行的关于预防卒中的序贯分析1至3因事件较少导致可信区间较宽而受到限制。随着数据的积累，分析4中的效应估计在视觉上稳定在降低25%的风险，可信区间越来越窄（2012年12月为-46%至+9%，2015年9月为-42%至-2%）。采用高维倾向评分的改进的数据适应性混杂调整在分析3时已达到稳定状态，且略接近随机临床试验结果（-39%）。达比加群起始使用者的大出血风险降低了28%（-35%至-20%），这一发现在分析2至9中保持稳定。结论 对达比加群预防卒中的有效性和安全性进行前瞻性监测，随着时间的推移能更精确地提供早期见解。
