Abstract 16388: Efficacy and Safety of Early Dalcetrapib Treatment on Lipid Profile and Markers of HDL Functionality in Patients Hospitalized for an Acute Coronary Syndrome - The dal-ACUTE Study
Introduction: The dal-ACUTE study assessed the efficacy and safety of the CETP modulator dalcetrapib in patients with a recent acute coronary syndrome (ACS) event.
Methods: In this Phase III, multi-center study, patients were randomized (1:1) to dalcetrapib 600 mg or placebo daily for 20 weeks within 1 week of hospitalization for an ACS event with 4-week safety follow up. The primary efficacy endpoint was percent change from baseline in HDL-C after 4 weeks. Secondary endpoints included blood lipid, lipoprotein and apolipoprotein levels and measures of HDL functionality (pre-β1-HDL and cholesterol efflux capacity). P<0.05 was considered statistically significant.
Results: 300 patients were randomized, within mean 3.9 days of the index ACS event. The majority of patients (75.2%) were statin naïve prior to the index event. By Week 4, dalcetrapib increased HDL-C by 33.7% vs placebo (P<0.0001), with a corresponding increase in ApoA1 of 11.8% (P<0.0001). LDL-C and ApoB levels declined post ACS but did not differ between placebo and dalcetrapib (both P>0.1). Pre-β1-HDL levels were unchanged vs placebo (P=0.42), however, total cholesterol efflux (% efflux over 4 hours) was significantly increased with dalcetrapib [LSM (95% CI) 9.5% (3.17, 16.18) P=0.003]. The change in cholesterol efflux correlated moderately with changes in HDL-C, pre-β1-HDL and ApoA1 (r = 0.42, 0.40 and 0.54 respectively, all P<0.0001). Dalcetrapib was generally well tolerated with a similar adverse event profile to placebo.
Conclusions: Dalcetrapib was well tolerated and significantly increased HDL-C and ApoA1 levels consistent with previous studies in stable patients. In the context of ACS, the variance (r2) in cholesterol efflux with dalcetrapib was approximately twice as strong with change in ApoA1 than with change in HDL-C levels. The clinical relevance of these different parameters will be assessed in other datasets.
- © 2012 by American Heart Association, Inc.