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Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies.
Dawwas, Ghadeer K; Hennessy, Sean; Brensinger, Colleen M; Deo, Rajat; Bilker, Warren B; Soprano, Samantha E; Dhopeshwarkar, Neil; Flory, James H; Bloomgarden, Zachary T; Aquilante, Christina L; Kimmel, Stephen E; Leonard, Charles E.
Afiliación
  • Dawwas GK; Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Hennessy S; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Brensinger CM; Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Deo R; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Bilker WB; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Soprano SE; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Dhopeshwarkar N; Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Flory JH; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Bloomgarden ZT; Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Aquilante CL; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Kimmel SE; Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Leonard CE; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Clin Pharmacol Ther ; 111(1): 227-242, 2022 01.
Article en En | MEDLINE | ID: mdl-34331322
In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high-dimensional propensity score (hdPS) matched, new-user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data-adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR (aHR), 2.01, 95% confidence interval (CI) 1.24-3.25). However, in Optum data, this finding was not present (aHR, 0.79, 95% CI 0.41-1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65, 95% CI 0.36-1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared with sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Muerte Súbita Cardíaca / Inhibidores de la Dipeptidil-Peptidasa IV Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Pharmacol Ther Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Muerte Súbita Cardíaca / Inhibidores de la Dipeptidil-Peptidasa IV Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Pharmacol Ther Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos