Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
Clinical Pharmacology & Toxicology, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
BMJ Open. 2022 Jun 13;12(6):e057991. doi: 10.1136/bmjopen-2021-057991.
Proton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole, pantoprazole, lansoprazole) when coprescribed with direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban). Our objective is to explore the risk of clinically relevant events, including bleeding, thromboembolic events and death, in patients prescribed DOACs while taking PPIs versus no PPI.
The protocol describes a retrospective cohort study of all Ontario residents aged 66 years or older with atrial fibrillation and at least one pharmacy dispensation for a DOAC identified using linked administrative healthcare databases covering 2009-2020. Ontario drug benefit dispensation records will be used to ascertain PPI exposure during DOAC therapy. The primary outcome is a composite of clinically relevant bleeding, thrombotic events or all-cause death. A minimum of 520 patients in total with at least one of the components of the composite outcome are needed. Poisson regression with a generalised estimating equation model will be used to calculate the adjusted incidence rate difference, incidence rate ratios 95% CI, adjusting for propensity for PPI use using inverse probability of treatment weights.
This research is exempt from REB review under section 45 of Ontario's Personal Health Information Protection Act. We will report our findings in a peer-reviewed biomedical journal and present them at conferences. The study will provide useful evidence to optimise the coprescription of DOACs and PPIs in practice.
质子泵抑制剂 (PPI) 被广泛用于上消化道出血的一级和二级预防。然而，在与直接口服抗凝剂 (DOAC；达比加群、利伐沙班、阿哌沙班、依度沙班) 联合使用时，PPI（奥美拉唑、雷贝拉唑、泮托拉唑、兰索拉唑）的总体净临床获益仍存在争议。我们的目的是探索在开具 DOAC 处方的同时使用 PPI 与不使用 PPI 的患者发生包括出血、血栓栓塞事件和死亡在内的临床相关事件的风险。
该方案描述了一项使用链接的行政医疗保健数据库（涵盖 2009 年至 2020 年）对所有 66 岁或以上患有心房颤动且至少有一次 DOAC 药物配药的安大略省居民进行的回顾性队列研究。安大略省药物福利配药记录将用于确定 DOAC 治疗期间 PPI 的暴露情况。主要结局是临床相关出血、血栓形成事件或全因死亡的复合结局。总共需要至少 520 名患者，其中至少有复合结局的一个组成部分。将使用广义估计方程模型的泊松回归来计算调整后的发病率差异、发病率比 95%CI，使用治疗反概率权重调整 PPI 使用的倾向。
根据安大略省个人健康信息保护法案第 45 条，本研究免于 REB 审查。我们将在同行评审的生物医学期刊上报告我们的研究结果，并在会议上展示。该研究将为优化 DOAC 和 PPI 的联合处方实践提供有用的证据。
