Evaluation of the dual peroxisome proliferator-activated receptor α/γ agonist aleglitazar to reduce cardiovascular events in patients with acute coronary syndrome and type 2 diabetes mellitus: Rationale and design of the AleCardio trial

Background Peroxisome proliferator-activated receptors (PPARs) regulate transcription of genes involved in glucose uptake, lipid metabolism, and inflammation. Aleglitazar is a potent dual PPAR agonist with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles and biomarkers of cardiovascular risk. The AleCardio trial examines whether the addition of aleglitazar to standard medical therapy reduces the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome. Study Design AleCardio is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. A total of 7,228 patients were randomized to aleglitazar 150 μg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to the first event of cardiovascular death, myocardial infarction, or stroke. Principal safety end points are hospitalization due to heart failure and changes in renal function. Treatment will continue until 7,000 patients are followed up for at least 2.5 years and 950 primary end point events are adjudicated. Conclusions AleCardio will establish whether the PPAR-α/γ agonist aleglitazar improves cardiovascular outcomes in patients with diabetes and high-risk coronary disease.