Dalcetrapib
Even NMR-measured HDL particle concentration, not just HDL-C, failed to predict cardiovascular risk in dal-Outcomes (Am Heart J 2020)
Original title: Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial
HDL particle concentration (HDLP), measured by nuclear magnetic resonance spectroscopy, has been proposed as a better cardiovascular risk predictor than HDL cholesterol in patients with established coronary disease. This nested case-cohort analysis of the dal-Outcomes trial (dalcetrapib versus placebo after acute coronary syndrome) measured total, large, medium and small HDLP at baseline in 476 patients who later had a major adverse cardiovascular event (MACE) and 902 controls. Baseline HDLP was not associated with MACE risk (adjusted hazard ratio 0.98 per SD, 95% CI, 0.84 to 1.15), nor was any HDLP subclass or HDL-C. Dalcetrapib raised HDL-C and total, medium and large HDLP while lowering small HDLP, but had no effect on MACE compared with placebo, and changes in HDLP or HDL-C from baseline to month 3 showed no association with MACE risk and no interaction with treatment assignment. The authors conclude neither baseline HDLP nor its change with dalcetrapib predicted cardiovascular risk after acute coronary syndrome.
Original abstract
Background: High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS).
Methods: The dal-Outcomes trial compared the CETP inhibitor dalcetrapib with placebo in patients with recent ACS. In a nested case-cohort analysis, total, large, medium, and small HDLPs were measured by nuclear magnetic resonance spectroscopy at baseline (4-12 weeks after ACS) in 476 cases with MACE and 902 controls. Hazard ratios (HRs; case-control) for 1-SD increment of HDLP or HDL-C at baseline were calculated with and without adjustment for demographic, clinical, laboratory, and treatment variables. Similarly, HRs for MACE were calculated for changes in HDLP or HDL-C from baseline to month 3 of assigned treatment.
Results: Over median follow-up of 28 months, the risk of MACE was not associated with baseline HDLP (adjusted HR = 0.98, 95% CI = 0.84-1.15, P = .81), any HDLP subclass, or HDL-C. Dalcetrapib increased HDL-C and total, medium, and large HDLP and decreased small HDLP but had no effect on MACE compared with placebo. There were no association of risk of MACE with change in HDLP or HDL-C and no interaction with assigned study treatment.
Conclusions: Neither baseline HDLP nor the change in HDLP on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS.
dalcetrapibHDL biologyoutcomes trials
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.