Rosiglitazone and the risk of MI or cardiovascular disease

Nissen SE, Wolski K. N Engl J Med 2007;356:2457-71. DOI: 10.1056/NEJMoa072761

Recognising that although rosiglitazone is widely used to treat patients with type-2 diabetes, the authors of this study wished to determine its effect on cardiovascular morbidity and mortality.The mode of enquiry used was a systematic review of existing studies. Searches were undertaken of the published literature, the website of the US Food & Drug Administration and a clinical trials registry maintained by a pharmaceutical company. Criteria for inclusion included a study duration of more than 24 weeks, the use of a randomised control group not receiving rosiglitazone, and the availability of outcome data for MI and death from cardiovascular causes. Ultimately, 42 trials met the inclusion criteria. The results were combined by means of a fixed-effects model.

In the trials, the mean age of the subjects was approximately 56 years and the mean baseline HbA1c level was approximately 8.2 per cent. In the rosiglitazone group, as compared with the control group, the odds ratio for MI was 1.43 (95 per cent CI, 1.03-1.98, P=0.03) and that for death from cardiovascular causes was 1.64 (95 per cent CI, 0.98-2.74, P=0.06).

The authors found that rosiglitazone was associated with a significant increase in the risk of MI and with an increase in the risk of death from cardiovascular causes that had borderline significance. The study was limited by lack of access to original source data, which would have enabled more precise analysis.

Despite the limitations, the authors suggest that patients and providers should consider the potential for serious adverse cardiovascular effects of rosiglitazone for type-2 diabetes.

There are several limitations to this meta-analysis. The study involved pooling the results of a group of trials that were not originally intended to explore cardiovascular outcomes. Many of these trials were small and short-term, resulting in few adverse cardiovascular events or deaths. Furthermore, the authors had no access to original source data for any of these trials, which prevented the use of more statistically powerful analysis.

The results suggest that clinicians should exercise caution in using this class of drug. Clearly, until there is prospective evidence from completed randomised controlled studies designed to evaluate cardiovascular outcomes for these drugs, clinicians should remember the maxim 'first do no harm' and resist the potential of optimism bias.

- Dr Rubin Minas is a GPSI in cardiology in Gillingham, Kent, and Medway PCT lead

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