Abstract 12636: Plasma Aldosterone Levels Are Not Associated With Cardiovascular Events: Insights from the ACCELERATE Trial.

Background: The failure of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib was associated with off target increased plasma aldosterone levels (PAL). The potent CETP inhibitor evacetrapib failed to show clinical benefit in a large randomized control trial. We sought to evaluate the impact of evacetrapib on PAL in a subset of the ACCELERATE trial and determine the association between PAL and major adverse cardiovascular outcomes (MACE). Methods: We included all patients who had a central laboratory measured PAL drawn per study protocol. We determined the impact of evacetrapib exposure compared to placebo on PAL levels following 12 months of exposure. Utilizing baseline and post-exposure aldosterone levels, a Kaplan-Meier hazards model generated hazard ratios (HR) for the risk of MACE (composite of cardiovascular death (CV), non-fatal myocardial infarction (MI), stroke, hospitalization for unstable angina, and revascularization) with increasing quartile of baseline PAL and percent change in PAL at follow-up. Results: Amongst 12,092 patients in ACCELERATE, 1,624 patients had a PAL drawn. The average age of the study population was 65.2 years and 75.7% male with a mean body mass index of 31.9. At baseline, 93.7% were hypertensive, 73.3% were diabetic, and 57.6% had a prior MI. Baseline PAL (85.2 [43, 150] vs. 86.8 [43, 155] pmol/L, p=0.81) and follow-up percent change (13.6% [-29, 88] vs. 17.9% [-24, 87], p=0.23) were similar between those who received evacetrapib and placebo. During a median follow-up of 28 months, the primary endpoint occurred in 263 patients (16.2%) with all-cause mortality occurring in 78 patients (4.8%). The HR for increasing quartile of the log of baseline PAL or percent change in PAL at follow-up were not significant for MACE (Table 1). Conclusions: Exposure to evacetrapib did not result in significant change in PAL compared to placebo. Among patients with high risk vascular disease, PAL was not a predictor for CV events. [ABSTRACT FROM AUTHOR]