The Pharmaceutical Journal
Vol 278 No 7456 p697
16 June 2007

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Cardiovascular risks of rosiglitazone still unclear

Interim findings from an ongoing study of the effects of rosiglitazone on risk of admission to hospital or death from cardiovascular causes are inconclusive, according to research published online in The New England Journal of Medicine (5 June 2007).

The interim analysis of the GlaxoSmithKline-sponsored study (RECORD) was originally unscheduled but published because “the current totality of evidence needs to be made available”. This follows the recent publication of a meta-analysis (PJ, 26 May, p600), in which an increased risk of myocardial infarction for people with diabetes taking rosiglitazone was identified.

The researchers conducted an open-label, non-inferiority trial involving 4,447 patients with type 2 diabetes who had inadequate glycaemic control while receiving metformin or a sulphonylurea. Patients were randomised to receive add-on rosiglitazone or a combination of metformin and sulphonylurea. The primary endpoint was admission to hospital or death from cardiovascular causes.

After a mean follow-up of 3.75 years, 217 patients in the rosiglitazone group and 202 in the control group were judged to have met the primary endpoint (hazard ratio 1.08, 95 per cent confidence interval 0.89–1.31; P=0.43). A further 50 patients in the rosiglitazone group and 41 patients in the control group had potential primary events reported by investigators but awaiting adjudication (hazard ratio 1.11; 0.93–1.32; P=0.26).

For myocardial infarction, the hazard ratio for adjudicated plus pending events was 1.23 (0.81–1.86; P=0.34), say the researchers. Patients in the rosiglitazone group had a higher risk of congestive heart failure than those in the control group (2.15, 1.30–3.57; P=0.003), they add.

The researchers acknowledge that a high loss to follow-up and low rate of primary endpoint events meant that the study had less statistical power than initially planned. “The data do not allow a conclusion as to whether treatment with rosiglitazone results in a higher rate of myocardial infarction than does therapy with metformin or a sulphonylurea,” they conclude.

The author of an accompanying editorial comments: “Unless further studies can provide convincing assurance that treatment with rosiglitazone does not increase the risk of cardiovascular disease, the largely circumstantial evidence of the meta-analyses and the non-significant trend in the current report from the RECORD trial must be taken seriously.”