Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis

Background Obesity and hypercholesterolemia independently increase cardiovascular disease risk. This analysis evaluated the efficacy and safety of bempedoic acid in people with obesity participating in the CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL‐Inhibiting Regimen) Outcomes...

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Main Authors: Harold E. Bays, LeAnne Bloedon, Danielle Brennan, Lei Lei, A. Michael Lincoff, Stephen J. Nicholls, Jorge Plutzky, Heather A. Powell, Steven E. Nissen
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.037898
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author Harold E. Bays
LeAnne Bloedon
Danielle Brennan
Lei Lei
A. Michael Lincoff
Stephen J. Nicholls
Jorge Plutzky
Heather A. Powell
Steven E. Nissen
author_facet Harold E. Bays
LeAnne Bloedon
Danielle Brennan
Lei Lei
A. Michael Lincoff
Stephen J. Nicholls
Jorge Plutzky
Heather A. Powell
Steven E. Nissen
author_sort Harold E. Bays
collection DOAJ
description Background Obesity and hypercholesterolemia independently increase cardiovascular disease risk. This analysis evaluated the efficacy and safety of bempedoic acid in people with obesity participating in the CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL‐Inhibiting Regimen) Outcomes trial. Methods CLEAR Outcomes randomized 13 970 patients to daily bempedoic acid 180 mg or placebo. Exploratory outcomes including major adverse cardiovascular events‐4 (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization), low‐density lipoprotein cholesterol, hs‐CRP (high‐sensitivity C‐reactive protein), weight change, and safety were assessed over a median of 40.7 months in 6177 patients with baseline body mass index ≥30 kg/m2. Results In people with obesity, bempedoic acid resulted in placebo‐corrected reductions in low‐density lipoprotein cholesterol of −22.5% and hs‐CRP of −23.2% at 6 months. Bempedoic acid treatment resulted in a major adverse cardiovascular events‐4 reduction of 23% (hazard ratio [HR], 0.77 [95% CI, 0.67–0.89]) versus placebo. Nonfatal and fatal MI were reduced by 32% (HR, 0.68 [95% CI, 0.53–0.86]), coronary revascularization was reduced by 24% (HR, 0.76 [95% CI, 0.63–0.92]), and fatal and nonfatal stroke were reduced by 36% (HR, 0.64 [95% CI, 0.45–0.89]) compared with placebo. At month 36, mean±SD change in weight from baseline was −2.3 (6.3) kg for bempedoic acid and −1.4 (6.1) kg for placebo. Adverse events were reported in 87.4% of bempedoic acid patients and 86.7% of placebo patients. The mean±SD change in uric acid at 6 months was 0.81 (1.26) mg/dL for bempedoic acid versus −0.04 (1.05) mg/dL for placebo. Conclusions Among people with obesity, bempedoic acid reduced major adverse cardiovascular events, low‐density lipoprotein cholesterol, and hs‐CRP, with a safety profile consistent with previous reports. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02993406.
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spelling doaj-art-6278a92d2d704fbc93ed1a07ea0cf5f42025-08-20T03:17:27ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114410.1161/JAHA.124.037898Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset AnalysisHarold E. Bays0LeAnne Bloedon1Danielle Brennan2Lei Lei3A. Michael Lincoff4Stephen J. Nicholls5Jorge Plutzky6Heather A. Powell7Steven E. Nissen8Louisville Metabolic and Atherosclerosis Research Center Louisville KYEsperion Therapeutics, Inc. Ann Arbor MICleveland Clinic Cleveland OHEsperion Therapeutics, Inc. Ann Arbor MICleveland Clinic Cleveland OHVictorian Heart Institute Monash University Melbourne AustraliaBrigham and Women’s Hospital, Harvard University Boston MAEsperion Therapeutics, Inc. Ann Arbor MICleveland Clinic Cleveland OHBackground Obesity and hypercholesterolemia independently increase cardiovascular disease risk. This analysis evaluated the efficacy and safety of bempedoic acid in people with obesity participating in the CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL‐Inhibiting Regimen) Outcomes trial. Methods CLEAR Outcomes randomized 13 970 patients to daily bempedoic acid 180 mg or placebo. Exploratory outcomes including major adverse cardiovascular events‐4 (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization), low‐density lipoprotein cholesterol, hs‐CRP (high‐sensitivity C‐reactive protein), weight change, and safety were assessed over a median of 40.7 months in 6177 patients with baseline body mass index ≥30 kg/m2. Results In people with obesity, bempedoic acid resulted in placebo‐corrected reductions in low‐density lipoprotein cholesterol of −22.5% and hs‐CRP of −23.2% at 6 months. Bempedoic acid treatment resulted in a major adverse cardiovascular events‐4 reduction of 23% (hazard ratio [HR], 0.77 [95% CI, 0.67–0.89]) versus placebo. Nonfatal and fatal MI were reduced by 32% (HR, 0.68 [95% CI, 0.53–0.86]), coronary revascularization was reduced by 24% (HR, 0.76 [95% CI, 0.63–0.92]), and fatal and nonfatal stroke were reduced by 36% (HR, 0.64 [95% CI, 0.45–0.89]) compared with placebo. At month 36, mean±SD change in weight from baseline was −2.3 (6.3) kg for bempedoic acid and −1.4 (6.1) kg for placebo. Adverse events were reported in 87.4% of bempedoic acid patients and 86.7% of placebo patients. The mean±SD change in uric acid at 6 months was 0.81 (1.26) mg/dL for bempedoic acid versus −0.04 (1.05) mg/dL for placebo. Conclusions Among people with obesity, bempedoic acid reduced major adverse cardiovascular events, low‐density lipoprotein cholesterol, and hs‐CRP, with a safety profile consistent with previous reports. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02993406.https://www.ahajournals.org/doi/10.1161/JAHA.124.037898bempedoic acidcardiovascular diseasecardiovascular risklipid loweringobesitystatin intolerance
spellingShingle Harold E. Bays
LeAnne Bloedon
Danielle Brennan
Lei Lei
A. Michael Lincoff
Stephen J. Nicholls
Jorge Plutzky
Heather A. Powell
Steven E. Nissen
Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
bempedoic acid
cardiovascular disease
cardiovascular risk
lipid lowering
obesity
statin intolerance
title Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
title_full Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
title_fullStr Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
title_full_unstemmed Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
title_short Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis
title_sort bempedoic acid for prevention of cardiovascular events in people with obesity a clear outcomes subset analysis
topic bempedoic acid
cardiovascular disease
cardiovascular risk
lipid lowering
obesity
statin intolerance
url https://www.ahajournals.org/doi/10.1161/JAHA.124.037898
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