The Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive)

Charbonnel B, Dormandy J, Erdmann E, Massi-Benedetti M, Skene A. Diabetes Care. 2004;27:1647-1653.

Type 2 diabetes is associated with significant cardiovascular morbidity and mortality and is considered an independent risk factor for cardiovascular disease. However, the effect of glucose-lowering medication on macrovascular disease among people with type 2 diabetes has yet to be demonstrated. This paper outlines baseline data and design of the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive), 1 of 3 studies currently being carried out to study the effect of pioglitazone (a thiazolidinedione [TZD]) on atherosclerosis among people with type 2 diabetes. The purpose of this ongoing, randomized, double-blind outcome study is to determine whether pioglitazone as an add-on therapy in patients with type 2 diabetes taking medication for glycemic, lipidemic, and hypertensive management will reduce macrovascular mortality and morbidity in high-risk subjects. A total of 5238 patients from 19 countries have been randomized to 1 of 2 groups: pioglitazone (15 mg to 45 mg) or placebo. Patients with type 2 diabetes were eligible for inclusion in the study if they had an A1C above 6.5% and were currently being treated with lifestyle changes, oral blood glucose-lowering agents other than TZDs, or a combination of oral agents (other than TZDs) and insulin. For study entry, subjects with type 2 diabetes also were required to meet one or more of the following criteria: history of myocardial infarction (>6 months); history of coronary artery revascularization, stroke, or acute coronary syndrome (>3 months); other evidence of coronary artery disease; or peripheral arterial occlusive disease. Primary study endpoint is time from randomization to occurrence of a new macrovascular event or death. The researchers are confident that enrolled subjects are typical of those at risk of a further macrovascular event and are therefore suitable for inclusion in the study. The results of this study will provide insight into the role of pioglitazone in the secondary prevention of cardiovascular disease among people with type 2 diabetes.