A new European trial of pioglitazone that will evaluate cardiovascular morbidity and mortality in patients with known cardiovascular disease and type 2 diabetes has enrolled 5,238 patients, according to an article in the July issue of Diabetes Care.

The study is called PROspective PioglitAzone Clinical Trial In MacroVascular Events Study (PROactive); eligible patients had one or more cardiovascular events before enrollment such as myocardial infarction, coronary artery bypass surgery, or stroke.

Study design is a randomized, double-blind, placebo-controlled outcome study assessing the incidence of cardiovascular complications of diabetes, e.g., myocardial infarction, coronary artery bypass surgery or stroke, as well as overall mortality. The primary endpoint variable is the time from randomization to the first occurrence of any of the events in the composite endpoint, including death and major macrovascular events. Pioglitazone or placebo is given as add-on therapy to existing diabetes management (including diet and exercise and other diabetes medications).

“Major studies have shown that sustained improvements in glycemic control significantly reduce the risk of some microvascular complications, but data remain inconclusive that intervention with conventional glucose-lowering agents is successful in modifying macrovascular disease,” said John Dormandy, MD, chairman of the steering committee. “Recent studies have shown ACTOS has a beneficial effect on markers of cardiovascular risk, such as atherogenic lipids and c-reactive protein. Through PROactive, we will determine if the beneficial effects of ACTOS on cardiovascular risk factors translate into a reduction in cardiovascular mortality and morbidity in a high-risk population of patients with type 2 diabetes.”

Type 2 diabetes is associated with a two- to four-fold increase in cardiovascular disease as well as other cardiovascular risk factors such as hypertension and cholesterol disorders. Additionally, heart disease is the leading cause of mortality and morbidity for patients with type 2 diabetes.

“Previous studies have suggested ACTOS can provide benefits extending beyond improvements in glucose levels,” said John Yates, M.D., M.R.C.P., representing the drug manufacturer. “Physicians who treat patients with type 2 diabetes face increasing challenges helping their patients manage cardiovascular risk factors. PROactive should generate important insights into whether the drug can play a larger role in the management of this devastating disease.”

In several large-scale trials, pioglitazone consistently improved components of diabetic dyslipidemia. Smaller, mechanistic studies have shown statistically significant changes in small, dense LDL cholesterol and in C-reactive protein.