Rosiglitazone Evaluated for Cardiovascular Outcomes — An Interim Analysis
Philip D. Home, D.M., D.Phil., Stuart J. Pocock, Ph.D., Henning Beck-Nielsen, D.M.S.C., Ramón Gomis, M.D., Ph.D., Markolf Hanefeld, M.D., Ph.D., Nigel P. Jones, M.A., Michel Komajda, M.D., John J.V. McMurray, M.D., for the RECORD Study Group
Background A recent meta-analysis raised concern regarding anincreased risk of myocardial infarction and death from cardiovascularcauses associated with rosiglitazone treatment of type 2 diabetes.
Methods We conducted an unplanned interim analysis of a randomized,multicenter, open-label, noninferiority trial involving 4447patients with type 2 diabetes who had inadequate glycemic controlwhile receiving metformin or sulfonylurea, in which 2220 patientswere assigned to receive add-on rosiglitazone (rosiglitazonegroup), and 2227 to receive a combination of metformin plussulfonylurea (control group). The primary end point was hospitalizationor death from cardiovascular causes.
Results Because the mean follow-up was only 3.75 years, ourinterim analysis had limited statistical power to detect treatmentdifferences. A total of 217 patients in the rosiglitazone groupand 202 patients in the control group had the adjudicated primaryend 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 wereno statistically significant differences between the rosiglitazonegroup and the control group regarding myocardial infarctionand death from cardiovascular causes or any cause. There weremore patients with heart failure in the rosiglitazone groupthan in the control group (hazard ratio, 2.15; 95% CI, 1.30to 3.57).
Conclusions Our interim findings from this ongoing study wereinconclusive regarding the effect of rosiglitazone on the overallrisk of hospitalization or death from cardiovascular causes.There was no evidence of any increase in death from either cardiovascularcauses or all causes. Rosiglitazone was associated with an increasedrisk of heart failure. The data were insufficient to determinewhether the drug was associated with an increase in the riskof myocardial infarction. (ClinicalTrials.gov number, NCT00379769
[ClinicalTrials.gov]
.)
Source Information
From Newcastle Diabetes Centre and Newcastle University, Newcastle upon Tyne, United Kingdom (P.D.H.); the Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London (S.J.P.); the Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark (H.B.-N.); Hospital Clinic, University of Barcelona, Barcelona (R.G.); Zentrum für Klinische Studien Forschungsbereich Endokrinologie und Stoffwechsel, Dresden, Germany (M.H.); GlaxoSmithKline Pharmaceuticals, Harlow, United Kingdom (N.P.J.); Université Pierre et Marie Curie Paris 6 and Hôpital Pitié–Salpêtrière, Paris (M.K.); and the Department of Cardiology, University of Glasgow, Western Infirmary, Glasgow (J.J.V.M.). This article (10.1056/NEJMoa073394) was published at www.nejm.org on June 5, 2007.
Address reprint requests to Dr. Home at SCMS-Diabetes, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom, or at philip.home{at}newcastle.ac.uk.
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