• Steven E Nissen, A Michael Lincoff, Danielle Brennan, Kausik K Ray, Denise Mason, KasteleinJohn J PJJP0000-0003-2018-4532From the Cleveland Clinic, Cleveland (S.E.N., A.M.L., D.B., D.M., L.C., V.M., J.M., D.D.); Imperial College London, London (K.K.R.); University of Amsterdam Academic Medical Center, Amsterdam (J.J.P.K.), and Universi, Paul D Thompson, Peter Libby, Leslie Cho, Jorge Plutzky, Harold E Bays, Patrick M Moriarty, Venu Menon, Diederick E Grobbee, Michael J Louie, Chien-Feng Chen, Na Li, LeAnne Bloedon, Paula Robinson, Maggie Horner, William J Sasiela, Jackie McCluskey, Deborah Davey, Pedro Fajardo-Campos, Predrag Petrovic, Jan Fedacko, Witold Zmuda, Yury Lukyanov, Stephen J Nicholls, and CLEAR Outcomes Investigators.
• From the Cleveland Clinic, Cleveland (S.E.N., A.M.L., D.B., D.M., L.C., V.M., J.M., D.D.); Imperial College London, London (K.K.R.); University of Amsterdam Academic Medical Center, Amsterdam (J.J.P.K.), and University Medical Center Utrecht, Utrecht (D.E.G.) - both in the Netherlands; Hartford Hospital, Hartford, CT (P.D.T.); Brigham and Women's Hospital, Harvard Medical School, Boston (P.L., J.P.); Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); University of Kansas Medical Center, Kansas City (P.M.M.); Esperion Therapeutics, Ann Arbor, MI (M.J.L., C.-F.C., N.L., L.B., P.R., M.H., W.J.S.); Centro de Investigación Cardiovascular y Metabólica, Tijuana, Mexico (P.F.-C.); General Hospital Sveti Luka, Smederevo, Serbia (P.P.); Center of Clinical and Preclinical Research Medipark, Pavol Jozef Šafárik University, Košice, Slovakia (J.F.); Medicome, Oświęcim, Poland (W.Z.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (Y.L.); and Victorian Heart Institute, Monash University, Melbourne, VIC, Australia (S.J.N.).
• N. Engl. J. Med. 2023 Apr 13; 388 (15): 135313641353-1364.

BackgroundBempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.MethodsWe conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.ResultsA total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.ConclusionsAmong statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).Copyright © 2023 Massachusetts Medical Society.

43 keywords...

hide…