In response to recent attention to potential cardiovascular risks associated with the use of rosiglitazone (NEJM May 21, 2007) investigators for the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial have published an unplanned interim analysis. RECORD is a 6-year, open-label study of patients with inadequate blood glucose control on metformin or sulfonylurea alone, designed to determine if a glucose control strategy that included rosiglitazone was noninferior to a strategy that did not include rosiglitazone. Subjects were randomized to receive either rosiglitazone plus sulfonylurea, rosiglitazone plus metformin, or metformin plus sulfonylurea. If glucose control was still inadequate at the maximum tolerated doses, then a third drug was added to the regimen of patients in the rosiglitazone groups, or insulin was started in patients in the nonrosiglitazone group. According to the study design, the rosiglitazone
strategy would be considered noninferior if the increased risk for the primary endpoint -- hospitalization or death from cardiovascular causes -- was no greater than 20%.
In all, 4458 patients were enrolled from April 2001 through April 2003; 10% were lost to follow-up. At a mean follow-up time of 3.75 years, the primary endpoint occurred in 217 patients in the rosiglitazone group compared with 202 patients in the nonrosiglitazone group (hazard ratio, 1.08). No significant between-group differences were found in rates of acute MI, death from CV causes or any cause, or a composite of CV death, MI, and stroke; however, the study was underpowered to detect such differences. Patients in the rosiglitazone group had a significantly increased risk for congestive heart failure (HR, 2.24).
This study adds little to the current debate about rosiglitazone. It is inconclusive and cannot exclude a clinically meaningful hazard with respect to CV outcomes. The rationale for using rosiglitazone while its safety is under debate remains unclear
http://www.diabetes.org/uedocuments/pr-ada-rosiglitazone-statement-060607.pdf
Please Click the links below to New York Times and NEJM for more info
http://www.nytimes.com/2007/06/06/health/06fda.html?ei=5070&en=032fd7f8c5b6bebc&ex=
1181793600&adxnnl=1&emc=eta1&adxnnlx=1181152963-eDTNauYQe3H40UL6a2tqDg
Original Article: Rosiglitazone Evaluated for Cardiovascular Outcomes --
An Interim Analysis
P.D. Home and Others
http://content.nejm.org/cgi/content/full/NEJMoa073394
Editorial: Rosiglitazone -- Continued Uncertainty about Safety
J.M. Drazen, S. Morrissey, and G.D. Curfman
http://content.nejm.org/cgi/content/full/NEJMe078118
Editorial: Rosiglitazone and Cardiotoxicity -- Weighing the Evidence D.M. Nathan
http://content.nejm.org/cgi/content/full/NEJMe078117
Editorial: The Record on Rosiglitazone and the Risk of Myocardial Infarction
B.M. Psaty and C.D. Furberg
http://content.nejm.org/cgi/content/full/NEJMe078116
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