Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis

N Engl J Med. 2007 Jul 5;357(1):28-38. doi: 10.1056/NEJMoa073394. Epub 2007 Jun 5.

Abstract

Background: A recent meta-analysis raised concern regarding an increased risk of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes.

Methods: We conducted an unplanned interim analysis of a randomized, multicenter, open-label, noninferiority trial involving 4447 patients with type 2 diabetes who had inadequate glycemic control while receiving metformin or sulfonylurea, in which 2220 patients were assigned to receive add-on rosiglitazone (rosiglitazone group), and 2227 to receive a combination of metformin plus sulfonylurea (control group). The primary end point was hospitalization or death from cardiovascular causes.

Results: Because the mean follow-up was only 3.75 years, our interim analysis had limited statistical power to detect treatment differences. A total of 217 patients in the rosiglitazone group and 202 patients in the control group had the adjudicated primary end point (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.31). After the inclusion of end points pending adjudication, the hazard ratio was 1.11 (95% CI, 0.93 to 1.32). There were no statistically significant differences between the rosiglitazone group and the control group regarding myocardial infarction and death from cardiovascular causes or any cause. There were more patients with heart failure in the rosiglitazone group than in the control group (hazard ratio, 2.15; 95% CI, 1.30 to 3.57).

Conclusions: Our interim findings from this ongoing study were inconclusive regarding the effect of rosiglitazone on the overall risk of hospitalization or death from cardiovascular causes. There was no evidence of any increase in death from either cardiovascular causes or all causes. Rosiglitazone was associated with an increased risk of heart failure. The data were insufficient to determine whether the drug was associated with an increase in the risk of myocardial infarction. (ClinicalTrials.gov number, NCT00379769 [ClinicalTrials.gov].).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Failure / chemically induced*
  • Hospitalization
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Risk
  • Rosiglitazone
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use

Substances

  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00379769