Author Affiliations: Cardiology, Centre Hospitalier Bichat-Claude Bernard (Dr Steg) and INSERM U695, Université Paris VII Faculté de Médecine X Bichat (Dr Marre), Paris, France. Dr Steg is also Editor, JAMA-français.
Cardiovascular events, particularly acute myocardial infarction and stroke, are the main causes of death in patients with diabetes. Whether stringent glucose control and use of specific glucose-lowering drugs reduce this risk has remained a controversial issue for decades.1,2 Thus, adequately powered randomized clinical trials are now required to study the effect of new antidiabetic drugs on cardiovascular death, myocardial infarction, and stroke. One of these studies was the Proactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) trial, which compared pioglitazone with placebo in addition to standard glucose-lowering drugs in more than 5000 patients.3 In the Proactive trial, treatment with pioglitazone failed to reduce significantly the primary composite end point of death, myocardial infarction, stroke, revascularization, and amputation, even though the secondary end point of death, myocardial infarction, and stroke was reduced (hazard ratio [HR]; 0.84, 95% confidence interval [CI], 0.72-0.98; P = .027). A patient-level meta-analysis of the 19 randomized, double-blind controlled trials of pioglitazone showed consistent results for reducing cardiovascular events, with an HR of 0.82 (95% CI, 0.72-0.94; P = .005) but at the price of an excess of serious heart failure (HR, 1.41; 95% CI, 1.14-1.76; P = .002).4
Steg PG, Marre M. Does PERISCOPE Provide a New Perspective on Diabetic Treatment?. JAMA. 2008;299(13):1603-1604. doi:10.1001/jama.299.13.1603