Key result
Screening identifies 14 antithrombotic drug interaction signals for bleeding, but only four appear biologically plausible.
Why the study?
Drug-drug interaction evidence from community-dwelling populations may not generalize to nursing home residents, and bleeding signals involving clopidogrel and oral anticoagulants remain incompletely characterized in this setting.
Does concomitant use of candidate precipitant medications increase major bleeding in nursing home residents taking clopidogrel or oral anticoagulants?
Observational (n=3,017)
Yes
Does concomitant use of candidate precipitant medications increase major bleeding in nursing home residents taking clopidogrel or oral anticoagulants?
High-throughput screening in nursing home residents identified several potential drug-drug interactions increasing bleeding risk with antithrombotics, though many signals likely reflect confounding by indication or protopathic bias rather than true pharmacological interactions.
Four plausible signals identified; hypothesis-generating and should not yet change prescribing in nursing home residents.
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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D’Amico et al. (2026) conducted an observational in Major bleeding in nursing home residents on antithrombotic therapy (n=3,017). Candidate precipitant medications vs. Periods of antithrombotic use without the precipitant medication was evaluated on Major bleeding. Self-controlled case series screening in nursing home residents identified 14 significant drug-drug interaction signals for major bleeding involving clopidogrel and oral anticoagulants, though expert review deemed only four biologically plausible.
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