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Clin Pharmacol Ther. 2019 May 20. doi: 10.1002/cpt.1507. [Epub ahead of print]

Clopidogrel Drug Interactions and Serious Bleeding: Generating Real-World Evidence via Automated High-Throughput Pharmacoepidemiologic Screening.

Author information

1
Department of Biostatistics, Epidemiology, and Informatics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2
Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3
Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

Few population-based studies have examined bleeding associated with clopidogrel drug-drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000-2015 Optum commercial health insurance claims to identify DDI signals. We performed self-controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13-3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.

PMID:
31106397
DOI:
10.1002/cpt.1507

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