Randomized comparison of the effects of rosiglitazone vs. placebo on peak integrated cardiovascular performance, cardiac structure, and function

Abstract

Aims: To assess the effect of rosiglitazone on cardiovascular performance and cardiac function.

Methods and results: One hundred and fifty type 2 diabetes patients with cardiovascular disease (CVD) or ≥ 1 other CVD risk factor were randomized to receive rosiglitazone vs. placebo for 6 months. The primary outcome was peak oxygen uptake indexed to fat-free mass (VO(2peak)-FFM) during maximum exercise. A subset of 102 subjects underwent cardiac magnetic resonance imaging (cMRI). On hundred and eight subjects completed the study, including 75 completing the cMRI substudy. No significant differences were observed in mean VO(2peak)-FFM between rosiglitazone and placebo (26.1 ± 7.0 vs. 27.6 ± 6.6 mL/kg-FFM/min; P = 0.26). Compared with placebo, the rosiglitazone group had lower hematocrit (38 vs. 41%; P < 0.001) and more peripheral oedema (53.7 vs. 33.3%; P = 0.03). In the cMRI substudy, compared with placebo, the rosiglitazone 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).

Conclusion: Rosiglitazone increased peripheral oedema but had no pernicious effects on cardiovascular performance or cardiac function, with modest improvement in selected cMRI measures. Changes in indirect markers of plasma volume suggest expansion with rosiglitazone.

Trial registration: clinicaltrials.gov identifier: NCT00424762.

Figures

Figure 1

Flow of patients through the trial (MRI, magnetic resonance imaging; CPX, cardiopulmonary exercise test).

Figure 2

Changes in mean haemoglobin A1c during the trial.

Figure 3

Mean peak oxygen consumption during maximal treadmill exercise (VO2peak) by treatment group at baseline and at study end (A) indexed to fat-free mass (primary endpoint); (B) indexed to total body weight; and (C) absolute measure without indexation.

Figure 4

Changes in selected parameters during the trial suggesting plasma volume expansion, including (A) weight; (B) hematocrit; (C) circulating brain natriuretic peptide; and (D) left ventricular end-diastolic volume.