biostudies-literatureLeonard CENIA NIH HHSNIDA NIH HHSNIGMS NIH HHS1171https://www.ebi.ac.uk/biostudies/studies/S-EPMC9501796biostudies-literatureUnknown58(9)<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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. <i>Conclusions</i>: We identified a potential &gt;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.Medicina (Kaunas, Lithuania)Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.PMC9501796R01 AG025152R01 AG060975T32GM075766T32 GM075766R01AG025152; R01AG060975; R01AG064589R01DA048001R01 DA048001R01 AG064589Hecht TEHSoprano SEAshcroft DMBilker WBDhopeshwarkar NNutescu EACarr MBrensinger CMChen CLeonard CEKasner SEHolbrook AHennessy SfalseThromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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. <i>Conclusions</i>: We identified a potential &gt;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.2022-01-01T00:00:00Z2022 Aug2025-04-18T22:29:01.666Z2024-10-19T08:20:53.586ZS-EPMC95017963614384810.3390/medicina58091171