Division of Clinical Pharmacology & Toxicology, McMaster University, Hamilton, ON, Canada.
Department of Health Research Methods, Evidence and Impact (formerly Clinical Epidemiology and Biostatistics), McMaster University, Hamilton, ON, Canada.
J Popul Ther Clin Pharmacol. 2020 Apr 13;27(2):e28-e44. doi: 10.15586/jptcp.v27i2.662.
Oral anticoagulants (OACs) are high-priority medications, frequently used with clinically important benefit and serious harm. Our objective was to compare the safety and effectiveness of direct-acting oral anticoagulants (DOACs) versus warfarin in a population where anticoagulation management and DOACs were readily available. A retrospective cohort study of all adults living in British Columbia with a diagnosis of atrial fibrillation and a first prescription for an OAC was conducted. Co-primary outcomes were ischemic stroke and systemic embolism, and major bleeding. Secondary outcomes included a net clinical outcome composite and analysis of discontinuation, switching, and key subgroups. We estimated the effects of treatment using time-to-event models with high-dimensional propensity score adjustment to control confounding. After adjustment for prescribing bias, a cohort (n = 20,113, 43.8% female, mean age 72.4 years) with a mean follow-up of 18.1 months showed that patients taking warfarin tended to be poorer, sicker, and less likely to have a cardiologist prescriber. Outcome event rates were not significantly different for DOACs compared to warfarin [adjusted rate ratio of 1.15 (0.91, 1.46) for systemic embolism, 0.94 (0.82, 1.08) for major bleeding, and 0.98 (0.90, 1.06) for net clinical outcome]. Only the effect of age on net clinical outcome met our strict criteria for predicting which group might be superior. Switch of drug class was associated with increased risk of events (p < 0.003). In this population, we found no difference in important clinical outcomes between warfarin and DOACs. Switching compared to not switching was associated with harm.
口服抗凝剂 (OACs) 是高度优先的药物，经常用于具有重要临床益处和严重危害的药物。我们的目标是比较直接作用的口服抗凝剂 (DOACs) 与华法林在抗凝管理和 DOACs 易于获得的人群中的安全性和有效性。这是一项回顾性队列研究，纳入了不列颠哥伦比亚省所有患有心房颤动且首次开处方使用 OAC 的成年人。主要结局是缺血性卒中和全身性栓塞，以及大出血。次要结局包括净临床结局综合分析以及停药、换药和关键亚组分析。我们使用具有高维倾向评分调整的时间事件模型来估计治疗效果，以控制混杂因素。在调整处方偏倚后，队列（n=20113，43.8%为女性，平均年龄 72.4 岁）的平均随访时间为 18.1 个月，结果表明服用华法林的患者往往更贫困、病情更严重，并且不太可能有心脏病专家开处方。与华法林相比，DOACs 的结局事件发生率没有显著差异[调整后的系统栓塞发生率比为 1.15（0.91，1.46），大出血发生率比为 0.94（0.82，1.08），净临床结局发生率比为 0.98（0.90，1.06）]。只有年龄对净临床结局的影响符合我们预测哪个组可能更优的严格标准。药物类别转换与事件风险增加相关（p<0.003）。在该人群中，我们未发现华法林和 DOACs 在重要临床结局方面存在差异。与不换药相比，换药与危害相关。
