Abstract

OBJECTIVE--- PROactive enrolled patients with type 2 diabetes and pre-existing cardiovascular disease. These patients were at high risk for heart failure (HF), so any therapeutic benefit could potentially be offset by risk of associated HF mortality. We analyzed the HF cases to assess the effects of treatment on morbidity and mortality following reports of serious HF (SHF).

RESEARCH DESIGN AND METHODS--- PROactive was an outcome study in 5,238 patients randomized to pioglitazone or placebo. Patients with NYHA Class II–IV HF at screening were excluded. A SAE of HF was defined as HF that required hospitalization or prolonged a hospitalization stay, was fatal or life threatening, or resulted in persistent significant disability or incapacity. HF risk was evaluated by multivariate regression.

RESULTS--- More pioglitazone (5.7%) than placebo patients (4.1%) had a SHF event during the study (P=0.007). However, mortality due to HF was similar (25/2605 [0.96%] for pioglitazone versus 22/2633 [0.84%] for placebo; P=0.639). Among patients with a SHF event, subsequent all-cause mortality was proportionately lower with pioglitazone (40/149 [26.8%]) versus 37/108 [34.3%] with placebo; P=0.1338). Proportionately fewer pioglitazone patients with SHF went on to have an event in the primary (47.7% with pioglitazone versus 57.4% with placebo; P=0.0593) or main secondary endpoint (34.9% with pioglitazone versus 47.2% with placebo; P=0.025).

CONCLUSIONS--- Although the incidence of SHF was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with SHF.