Abstract 3946: Morbidity After Reports of Serious Heart Failure in Type 2 Diabetes Patients With Underlying Cardiovascular Disease: Results From PROactive
Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular (CV) events and the development of heart failure (HF), which may be exacerbated by diabetes treatment. PROactive, a CV outcome study with a primary composite endpoint of 7 CV-related components, demonstrated a beneficial trend for pioglitazone (PIO) in reducing the risk of CV events in high-risk T2D patients. However, there were increased investigator reported serious heart failure (IRSHF) cases, which were not adjudicated study endpoints. We examined the effects of PIO on morbidity and mortality after reports of serious HF in PROactive. PROactive was a randomized, double-blind, outcome study in 5238 patients with T2D and macrovascular disease randomized to PIO or placebo (PBO) in addition to their existing glucose-lowering and concomitant CV medications, such as anti-hypertensives and diuretics. Starting dose was 15 mg (PIO or PBO) with forced titration to a maximum tolerated dose of 45 mg. Mean follow up was 34.5 months. Despite more IRSHF in the PIO group, the number of deaths or CV endpoints after serious HF was similar between treatment groups. Most IRSHF cases in both groups resolved, were not related to drug, and did not limit treatment. Of those who where on therapy at the time of diagnosis of HF, only 34 of the 113 patients still receiving PIO and 17 out of 89 receiving PBO at the time of IRSHF discontinued the study drug. Although long-term PIO treatment was associated with more reports of IRSHF, the absolute number of PIO patients who subsequently died or had a MI or stroke was similar compared to PBO in high-risk T2D patients. Therefore, the overall trend of reduced macrovascular events with PIO in PROactive is not diminished by HF sequelae in these high-risk patients.