{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:14:16Z","timestamp":1793297656858,"version":"4.5.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,7,11]]},"abstract":"\n Importance<\/jats:title>\n The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This masked, randomized clinical trial enrolled 13\u202f970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized to oral bempedoic acid, 180 mg daily (n\u2009=\u20092100), or matching placebo (n\u2009=\u20092106).<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures<\/jats:title>\n The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg\/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg\/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg\/L (21.5%), from a median baseline of 2.4 mg\/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89];\n P<\/jats:italic>\n \u2009=\u2009.002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT02993406<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2023.9696","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T15:31:07Z","timestamp":1687620667000},"page":"131","source":"Crossref","is-referenced-by-count":142,"title":["Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients"],"prefix":"10.1001","volume":"330","author":[{"given":"Steven E.","family":"Nissen","sequence":"first","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venu","family":"Menon","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Victorian Heart Institute, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Brennan","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Laffin","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Ridker","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kausik K.","family":"Ray","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Mason","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. P.","family":"Kastelein","sequence":"additional","affiliation":[{"name":"University of Amsterdam Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Cho","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics Inc, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnne","family":"Foody","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics Inc, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Louie","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics Inc, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Michael","family":"Lincoff","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"10","key":"joi230067r1","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1016\/j.jacc.2019.03.010","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines.","volume":"74","author":"Arnett","year":"2019","journal-title":"J Am Coll Cardiol"},{"issue":"20","key":"joi230067r2","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1056\/NEJM199511163332001","article-title":"Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.","volume":"333","author":"Shepherd","year":"1995","journal-title":"N Engl J Med"},{"issue":"20","key":"joi230067r3","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1001\/jama.279.20.1615","article-title":"Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS\/TexCAPS.","volume":"279","author":"Downs","year":"1998","journal-title":"JAMA"},{"issue":"1","key":"joi230067r4","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1001\/jamainternmed.2016.7585","article-title":"Statins for primary prevention: the debate is intense, but the data are weak.","volume":"177","author":"Redberg","year":"2017","journal-title":"JAMA Intern Med"},{"key":"joi230067r5","doi-asserted-by":"publisher","first-page":"l5674","DOI":"10.1136\/bmj.l5674","article-title":"Statins for primary prevention of cardiovascular disease.","volume":"367","author":"Byrne","year":"2019","journal-title":"BMJ"},{"issue":"1","key":"joi230067r6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7326\/M18-1279","article-title":"Finding the balance between benefits and harms when using statins for primary prevention of cardiovascular disease: a modeling study.","volume":"170","author":"Yebyo","year":"2019","journal-title":"Ann Intern Med"},{"issue":"5","key":"joi230067r7","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1001\/jamainternmed.2022.0134","article-title":"Evaluating the association between low-density lipoprotein cholesterol reduction and relative and absolute effects of statin treatment: a systematic review and meta-analysis.","volume":"182","author":"Byrne","year":"2022","journal-title":"JAMA Intern Med"},{"key":"joi230067r8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.ahj.2017.08.005","article-title":"Lipid management in contemporary community practice: results from the Provider Assessment of Lipid Management (PALM) registry.","volume":"193","author":"Navar","year":"2017","journal-title":"Am Heart J"},{"issue":"2","key":"joi230067r9","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1097\/MAJ.0000000000000292","article-title":"Statin underuse and low prevalence of LDL-C control among US adults at high risk of coronary heart disease.","volume":"348","author":"Gamboa","year":"2014","journal-title":"Am J Med Sci"},{"issue":"5","key":"joi230067r10","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1001\/jamacardio.2023.0228","article-title":"Prevalence of statin use for primary prevention of atherosclerotic cardiovascular disease by race, ethnicity, and 10-year disease risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020.","volume":"8","author":"Jacobs","year":"2023","journal-title":"JAMA Cardiol"},{"issue":"15","key":"joi230067r11","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1056\/NEJMoa2215024","article-title":"Bempedoic acid and cardiovascular outcomes in statin-intolerant patients.","volume":"388","author":"Nissen","year":"2023","journal-title":"N Engl J Med"},{"key":"joi230067r12","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ahj.2020.10.060","article-title":"Rationale and design of the CLEAR Outcomes trial: evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance.","volume":"235","author":"Nicholls","year":"2021","journal-title":"Am Heart J"},{"issue":"6","key":"joi230067r13","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1001\/jama.297.6.611","article-title":"Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score.","volume":"297","author":"Ridker","year":"2007","journal-title":"JAMA"},{"issue":"11","key":"joi230067r14","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0195-668X(03)00114-3","article-title":"Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.","volume":"24","author":"Conroy","year":"2003","journal-title":"Eur Heart J"},{"issue":"5","key":"joi230067r15","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.118.004652","article-title":"Variation in lipid-lowering therapy use in patients with low-density lipoprotein cholesterol =190 mg\/dL: insights from the National Cardiovascular Data Registry\u2013Practice Innovation and Clinical Excellence Registry.","volume":"11","author":"Virani","year":"2018","journal-title":"Circ Cardiovasc Qual Outcomes"},{"issue":"4","key":"joi230067r16","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1001\/jamacardio.2016.5922","article-title":"Adoption of the 2013 American College of Cardiology\/American Heart Association cholesterol management guideline in cardiology practices nationwide.","volume":"2","author":"Pokharel","year":"2017","journal-title":"JAMA Cardiol"},{"key":"joi230067r17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.atherosclerosis.2016.11.025","article-title":"Extent of undertreatment and overtreatment with cholesterol-lowering therapy according to European guidelines in 92,348 Danes without ischemic cardiovascular disease and diabetes in 2004-2014.","volume":"257","author":"Langsted","year":"2017","journal-title":"Atherosclerosis"},{"issue":"7","key":"joi230067r18","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.011765","article-title":"Patient-reported reasons for declining or discontinuing statin therapy: insights from the PALM registry.","volume":"8","author":"Bradley","year":"2019","journal-title":"J Am Heart Assoc"},{"issue":"21","key":"joi230067r19","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1056\/NEJMoa1600176","article-title":"Cholesterol lowering in intermediate-risk persons without cardiovascular disease.","volume":"374","author":"Yusuf","year":"2016","journal-title":"N Engl J Med"},{"issue":"21","key":"joi230067r20","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.","volume":"359","author":"Ridker","year":"2008","journal-title":"N Engl J Med"},{"issue":"9841","key":"joi230067r21","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S0140-6736(12)60367-5","article-title":"The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.","volume":"380","author":"Mihaylova","year":"2012","journal-title":"Lancet"},{"issue":"12","key":"joi230067r22","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory therapy with canakinumab for atherosclerotic disease.","volume":"377","author":"Ridker","year":"2017","journal-title":"N Engl J Med"},{"issue":"26","key":"joi230067r23","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and safety of low-dose colchicine after myocardial infarction.","volume":"381","author":"Tardif","year":"2019","journal-title":"N Engl J Med"},{"issue":"19","key":"joi230067r24","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1056\/NEJMoa2021372","article-title":"Colchicine in patients with chronic coronary disease.","volume":"383","author":"Nidorf","year":"2020","journal-title":"N Engl J Med"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2806646\/jama_nissen_2023_oi_230067_1688654420.59513.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T11:01:17Z","timestamp":1689073277000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2806646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,11]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,7,11]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2023.9696","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742692531.793599786","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.742692531.793599940","asserted-by":"object"}]},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7,11]]}}}