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Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

ABSTRACT: Background and Objectives: Warfarin and a skeletal muscle relaxant are co-treatments in nearly a quarter-million annual United States (US) office visits. Despite international calls to minimize patient harm arising from anticoagulant drug interactions, scant data exist on clinical outcomes in real-world populations. We examined effects of concomitant use of warfarin and individual muscle relaxants on rates of hospitalization for thromboembolism among economically disadvantaged persons. Materials and Methods: Using 1999-2012 administrative data of four US state Medicaid programs, we conducted 16 retrospective self-controlled case series studies: half included concomitant users of warfarin + one of eight muscle relaxants; half included concomitant users of an inhaled corticosteroid (ICS) + one of eight muscle relaxants. The ICS analyses served as negative control comparisons. In each study, we calculated incidence rate ratios (IRRs) comparing thromboembolism rates in the co-exposed versus warfarin/ICS-only exposed person-time, adjusting for time-varying confounders. Results: Among ~70 million persons, we identified 8693 warfarin-treated subjects who concomitantly used a muscle relaxant, were hospitalized for thromboembolism, and met all other inclusion criteria. Time-varying confounder-adjusted IRRs ranged from 0.31 (95% confidence interval: 0.13-0.77) for metaxalone to 3.44 (95% confidence interval: 1.53-7.78) for tizanidine. The tizanidine finding was robust after quantitatively adjusting for negative control ICS findings, and in numerous prespecified secondary analyses. Conclusions: We identified a potential >3-fold increase in the rate of hospitalized thromboembolism in concomitant users of warfarin + tizanidine vs. warfarin alone. Alternative explanations for this finding include confounding by indication, a native effect of tizanidine, or chance.

SUBMITTER: Leonard CE

PROVIDER: S-EPMC9501796 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

Leonard Charles E CE Brensinger Colleen M CM Bilker Warren B WB Soprano Samantha E SE Dhopeshwarkar Neil N Hecht Todd E H TEH Kasner Scott E SE Nutescu Edith A EA Holbrook Anne A Carr Matthew M Ashcroft Darren M DM Chen Cheng C Hennessy Sean S

Medicina (Kaunas, Lithuania) 20220829 9

Background and Objectives: Warfarin and a skeletal muscle relaxant are co-treatments in nearly a quarter-million annual United States (US) office visits. Despite international calls to minimize patient harm arising from anticoagulant drug interactions, scant data exist on clinical outcomes in real-world populations. We examined effects of concomitant use of warfarin and individual muscle relaxants on rates of hospitalization for thromboembolism among economically disadvantaged persons. Materials ...[more]

PMID: 36143848

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Project description:BackgroundEmergency department (ED) patients with venous thromboembolism (VTE) are eventually treated with a standard dose of warfarin despite the fact that a number of patients are known to be sensitive to warfarin and may experience supra-therapeutic INRs and adverse bleeding events. Pharmacogenetics is an emerging field of medical practice that seeks to improve drug safety and efficacy in an individual patient by tailoring treatment to the patient's known genetic makeup.ObjectiveTo identify patients with risk for warfarin sensitivity among an ED population with VTE and to assess if the warfarin sensitivity mutations were of significant enough prevalence to be of clinical significance in customizing treatment of VTE. We sought in a pilot study to identify if testing for common CYP2C9 and VKORC1 single nucleotide polymorphisms (SNPs) in patients who were likely to begin warfarin treatment was feasible in an ED setting.MethodsA prospective study that identified and enrolled patients presenting to our ED with high clinical suspicion of VTE. Those with high clinical suspicion of VTE were defined as those who had a Doppler ultrasound or computed tomography pulmonary angiography (CTPA) ordered by the primary emergency physician. Blood was taken and processed to ascertain the following SNPs: CYP2C9*2, CYP2C9*3, and VKORC1 3673.ResultsOf the 194 patients enrolled, 132 (68.0%) had at least one known warfarin sensitivity mutation and 114 (58.8%) had the most clinically significant VKORC1 3673 mutation.ConclusionA majority of our patients had at least one mutation associated with the atypical metabolism of warfarin. Over half of our population had the most clinically significant VKORC1 3673 mutation. They would likely benefit from individualized warfarin dosing if ever needing anticoagulation. Our initial pilot study shows that allele frequencies of target warfarin sensitivity SNPs in our patient population are frequent enough to make initiation of personalized warfarin dosing feasible.

Dataset Information

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

Publications

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

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