The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety

Cardiovasc Diabetol. 2020 Feb 25;19(1):25. doi: 10.1186/s12933-020-00999-5.

Abstract

Background: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA).

Methods: We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999-2012) and a commercial health insurance plan (Optum Clinformatics | 2000-2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset.

Results: The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75-1.10) in Medicaid and 0.88 (0.61-1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54-0.93] and 1.16 [0.89-1.52] in men and women respectively, interaction term p-value = 0.01).

Conclusions: Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

Keywords: Cardiac arrhythmias; Cohort studies; Medicaid; Pharmacoepidemiology; Propensity score; Sudden cardiac death; Thiazolidinediones; Type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / epidemiology*
  • Arrhythmias, Cardiac / prevention & control
  • Databases, Factual
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / prevention & control
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Male
  • Medicaid
  • Middle Aged
  • Pioglitazone / adverse effects
  • Pioglitazone / therapeutic use*
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Rosiglitazone / adverse effects
  • Rosiglitazone / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Hypoglycemic Agents
  • Rosiglitazone
  • Pioglitazone