Drug-Drug Interaction Signals for Major Bleeding in Nursing Home Residents: High-Throughput Screening of Clopidogrel and Oral Anticoagulants.

IF 2.6 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2026-08-01 DOI:10.1002/pds.70441

Adam M D'Amico, Melissa R Riester, Charles E Leonard, Daniel A Harris, Lori A Daiello, Yu-Chia Sam Hsu, Douglas P Kiel, Meghan A Cupp, Kaleen N Hayes, Andrew R Zullo

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引用次数: 0

Abstract

Purpose: Nursing home (NH) residents are at high risk for major bleeding and are frequently exposed to complex medication regimens that may increase the likelihood of clinically important drug-drug interactions (DDIs). However, DDI evidence from community-dwelling populations may not generalize to NH residents, and real-world signals involving clopidogrel and oral anticoagulants remain incompletely characterized in this setting. We aimed to identify and interpret candidate DDI signals for major bleeding involving clopidogrel and oral anticoagulants among NH residents.

Methods: Using linked Minimum Data Set assessments and Medicare fee-for-service claims (2013-2020), we conducted high-throughput, self-controlled case series (SCCS) screening analyses for four object drugs (clopidogrel, apixaban, rivaroxaban, and warfarin) paired with candidate precipitant medications. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) comparing periods of concomitant use versus object drug use alone, applying semi-Bayes shrinkage to reduce false-positive signals. To aid interpretation, we incorporated two negative controls: a negative-control object drug (pravastatin) and a negative-control outcome (fall-related injury). A panel of experts evaluated signals for biological plausibility and potential bias.

Results: After semi-Bayes adjustment, 5/40 clopidogrel, 1/29 apixaban, 2/15 rivaroxaban, and 6/22 warfarin signals remained significant, and none did for pravastatin. Signals were also observed for fall-related injury. Experts identified only clopidogrel/sertraline and warfarin with cephalexin, sulfamethoxazole-trimethoprim, and furosemide as biologically plausible signals.

Conclusion: SCCS screening for DDIs in NH residents identified bleeding signals for clopidogrel and oral anticoagulants, but few were mechanistically coherent and fall-related injury signals suggested residual bias.

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疗养院居民大出血的药物-药物相互作用信号：氯吡格雷和口服抗凝剂的高通量筛选。

目的：养老院（NH）的居民大出血的风险很高，并且经常暴露于复杂的药物治疗方案，这可能会增加临床上重要的药物相互作用（ddi）的可能性。然而，来自社区居民的DDI证据可能无法推广到NH居民，并且涉及氯吡格雷和口服抗凝剂的现实信号在这种情况下仍然不完全表征。我们的目的是识别和解释NH居民中涉及氯吡格雷和口服抗凝剂的大出血的候选DDI信号。方法：使用最小数据集评估和医疗保险按服务收费索赔（2013-2020），我们对四种目标药物（氯吡格雷、阿哌沙班、利伐沙班和华法林）与候选沉淀药物配对进行了高通量、自我控制的病例系列（SCCS）筛选分析。我们估计了联合用药与单独用药期间的比率比（rr）和95%置信区间（ci），并应用半贝叶斯收缩来减少假阳性信号。为了帮助解释，我们纳入了两个阴性对照：阴性对照对象药物（普伐他汀）和阴性对照结果（跌倒相关损伤）。一个专家小组评估了信号的生物学合理性和潜在的偏见。结果：经半贝叶斯校正后，氯吡格雷5/40、阿哌沙班1/29、利伐沙班2/15、华法林6/22的信号仍然显著，普伐他汀无显著。也观察到与跌倒有关的损伤的信号。专家认为只有氯吡格雷/舍曲林和华法林与头孢氨苄、磺胺甲恶唑-甲氧苄啶和呋塞米是生物学上合理的信号。结论：SCCS筛查NH居民ddi发现氯吡格雷和口服抗凝剂的出血信号，但很少有机制一致，跌倒相关损伤信号提示残留偏差。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.