Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis

Pharmacoepidemiol Drug Saf. 2009 Jun;18(6):437-47. doi: 10.1002/pds.1722.

Abstract

Purpose: To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis.

Methods: We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality.

Results: 19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048).

Conclusions: Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.

Publication types

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

MeSH terms

  • Acute Disease
  • Cardiovascular Diseases / mortality
  • Cohort Studies
  • Data Interpretation, Statistical
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality*
  • Pioglitazone
  • Proportional Hazards Models
  • Retrospective Studies
  • Rosiglitazone
  • Stroke / mortality
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Pioglitazone