189-LB: LDL Cholesterol Reduction and Cardiovascular Outcomes in High-Risk Primary Prevention Patients

Abstract

Background: Current guidelines recommend reducing LDL cholesterol in patients at high risk for a first major adverse cardiovascular event (primary prevention). However, these recommendations are predominately based on clinical trials conducted many years ago. Most contemporary trials of LDL-cholesterol lowering therapies have enrolled only secondary prevention patients. Some authorities have questioned whether the benefits of cholesterol lowering exceed the harms in primary prevention patients. Currently, lipid-lowering therapies are underutilized in high-risk patients without a prior event, particularly in women and patients with diabetes. More than half of eligible patients are not currently receiving LDL-cholesterol lowering therapies. Methods: The CLEAR Outcomes trial reported cardiovascular outcomes for bempedoic acid treatment compared with placebo in a mixed population of primary and secondary prevention patients unable or unwilling to take guideline-recommended doses of statins (N=13,970). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization. The results of the CLEAR OUTCOMES trial were presented and simultaneously published in the NEJM on March 4. The hazard ratio for the primary end point for the full population was 0.87 (95% CI 0.79-0.96), P=0.004. Results: In the CLEAR Outcomes trial, 4206 patients (30%) met high risk primary prevention entry criteria, two thirds with diabetes. The HR in these primary prevention patients was lower than the HR for secondary prevention patients, 0.68 (95% CI 0.53-0.87), with a significant interaction P value (0.03). The current Late Breaking Trial will report detailed results for the primary and all key secondary endpoints for the 4206 patients enrolled based on high risk primary prevention criteria. Full results will be available in mid-April for simultaneous presentation and publication during the ADA meeting. Disclosure S. Nissen: Research Support; Eli Lilly and Company, AbbVie Inc., AstraZeneca, Bristol-Myers Squibb Company, ESPERION Therapeutics, Inc., New Amsterdam Pharma, Novartis, Patient-Centered Outcomes Research Institute, Silence Therapeutics. For the clear outcomes trial investigators: n/a. Funding National Heart, Lung, and Blood Institute (K23HL153774 to J.E.T.); University of Toronto (to B.R.S.)