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非甾体抗炎药与口服抗凝药物并用是否会增加大出血、中风和全身性栓塞的风险?

Does coprescribing nonsteroidal anti-inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism?

机构信息

Manchester Centre for Health Economics, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

NIHR Greater Manchester Patient Safety Translational Research Centre, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

出版信息

Br J Clin Pharmacol. 2022 Nov;88(11):4789-4811. doi: 10.1111/bcp.15371. Epub 2022 Jun 8.

Abstract

AIMS

To examine the risk of gastrointestinal (GI) bleeding, major bleeding, stroke and systemic embolism associated with prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) to adults receiving oral anticoagulant (OAC) therapy.

METHODS

We conducted a population-based cohort study in adults receiving OAC therapy using linked primary care (Clinical Practice Research Datalink GOLD) and hospital (Hospital Episodes Statistics) electronic health records. We used cause-specific Cox regression models with time-dependent NSAID treatment in a propensity score matched population to estimate the increased risk of GI bleeding, stroke, major bleeding and systemic embolism associated with NSAID use.

RESULTS

The matched cohort contained 3177 patients with OAC therapy alone and 3177 with at least 1 concomitant NSAID prescription. Compared with OAC therapy alone, concomitant prescription of NSAIDs with OACs was associated with increased risk of GI bleeding (hazard ratio [HR] 3.01, 95% confidence interval [CI] 1.63 to 5.55), stroke (HR 2.71, 95% CI 1.48 to 4.96) and major bleeding (HR 2.77, 95% CI 1.84 to 4.19). The association with systemic embolism did not reach statistical significance (HR 3.02, 95% CI 0.82 to 11.07). Sensitivity analyses indicated that the results were robust to changes in exclusion criteria and the choice of potential confounding variables.

CONCLUSION

When OACs are coprescribed with NSAIDs, the risk of adverse bleeding events increases and, simultaneously, the protective effect of OACs to prevent strokes reduces. There is a need for interventions that reduce hazardous prescribing of NSAIDs in people receiving OAC therapy.

摘要

目的

研究在接受口服抗凝剂 (OAC) 治疗的成年人中开具非甾体抗炎药 (NSAIDs) 的处方与胃肠道 (GI) 出血、大出血、中风和全身性栓塞相关的风险。

方法

我们在接受 OAC 治疗的成年人中进行了一项基于人群的队列研究,使用了链接的初级保健(临床实践研究数据链接 GOLD)和医院(医院发病统计)电子健康记录。我们在倾向评分匹配人群中使用基于因果的 Cox 回归模型,其中 NSAID 治疗是时间依赖性的,以估计与 NSAID 使用相关的 GI 出血、中风、大出血和全身性栓塞风险增加。

结果

匹配队列包含 3177 名仅接受 OAC 治疗的患者和 3177 名至少同时开具 NSAID 处方的患者。与单独接受 OAC 治疗相比,同时开具 NSAIDs 和 OACs 与 GI 出血风险增加相关(风险比 [HR] 3.01,95%置信区间 [CI] 1.63 至 5.55)、中风(HR 2.71,95% CI 1.48 至 4.96)和大出血(HR 2.77,95% CI 1.84 至 4.19)。与全身性栓塞的关联未达到统计学意义(HR 3.02,95% CI 0.82 至 11.07)。敏感性分析表明,结果在排除标准和潜在混杂变量选择的变化下具有稳健性。

结论

当 OAC 与 NSAIDs 同时开处方时,不良出血事件的风险增加,同时,OAC 预防中风的保护作用降低。需要采取干预措施,减少接受 OAC 治疗的人群中危险的 NSAID 处方。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262e/9796910/eeac4a395eb3/BCP-88-4789-g002.jpg

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