Abstract 980: Randomized Comparison of the Effects of Rosiglitazone versus Placebo on Peak Integrated Cardiovascular Performance, Cardiac Structure, and Function
Objective: Thiazolidinediones increase heart failure risk, but their cardiac effects remain unclear. We assessed the effect of rosiglitazone (Rsg) vs placebo (Plac) on cardiovascular performance, cardiac structure and function.
Methods: 150 patients with type 2 diabetes and either cardiovascular disease (CVD) or ≥1 additional CVD risk factor were randomized in a blinded, controlled trial to receive Rsg versus Plac, with assessments at baseline and after 6 months of study drug. The 1o outcome was peak oxygen uptake indexed to fat-free mass (VO2peak-FFM) during maximum exercise. A subset of 102 subjects underwent cardiac MRI.
Findings: No significant differences were observed in mean VO2peak-FFM between Rsg and Plac (26.1 +/− 7.0 vs. 27.6 +/− 6.6 ml/kg-FFM/min; p=0.26); nor were differences observed in absolute VO2peak nor scaled to total body mass (Figure⇓). Compared with Plac, Rsg was associated with numerically higher weight (100.8 vs. 97.3 kg; p=0.36); lower hematocrit (38 vs 41%; p<0.001); and more peripheral edema (53.7 vs 33.3%; p=0.03). In the cMRI substudy, compared with Plac, the Rsg group had larger end-diastolic volume (128.1 vs 112.0 ml; p=0.01) and stroke volume (83.7 vs. 72.9 ml; p=0.01), and a trend toward increased peak ventricular filling rate (79.4 vs. 60.5; p=0.07).
Interpretation: Despite increasing peripheral edema, rosiglitazone had no pernicious effects on cardiovascular performance or cardiac function, with modest improvement in selected measures of cardiac function. A number of measures suggest plasma volume expansion, which may underpin the observed heart failure with thiazolidinediones.