{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:48:40Z","timestamp":1792586920807,"version":"4.5.0"},"reference-count":27,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"\n Importance<\/jats:title>\n In patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare the long-term efficacy and safety of an alternative LDL cholesterol\u2013lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials comparing an alternative LDL cholesterol\u2013lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin\/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease). The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol\u2013lowering strategies. The primary analysis was based on a 1-stage approach.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio,\u20090.98; 95% CI, 0.84-1.15;\n P<\/jats:italic>\n \u2009=\u2009.82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg\/dL in the alternative strategy group and 68.5 (20.7) mg\/dL in the high-intensity statin strategy group (\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656];\n P<\/jats:italic>\n \u2009=\u2009.047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656];\n P<\/jats:italic>\n \u2009=\u2009.02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Results of this systematic review and individual patient data meta-analysis suggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance.<\/jats:p>\n <\/jats:sec>\n \n Study Registration<\/jats:title>\n \n PROSPERO\n CRD42024532550<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2024.3911","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:01:05Z","timestamp":1732100465000},"page":"137","source":"Crossref","is-referenced-by-count":28,"title":["Alternative LDL Cholesterol\u2013Lowering Strategy vs High-Intensity Statins in Atherosclerotic Cardiovascular Disease"],"prefix":"10.1001","volume":"10","author":[{"given":"Yong-Joon","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum-Kee","family":"Hong","sequence":"additional","affiliation":[{"name":"Gangnam Severance Hospital, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong Ho","family":"Yun","sequence":"additional","affiliation":[{"name":"Wonkwang University Hospital, Iksan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong Chol","family":"Kang","sequence":"additional","affiliation":[{"name":"Gachon University College of Medicine, Incheon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Jun","family":"Hong","sequence":"additional","affiliation":[{"name":"Korea University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hyup","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Jin","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul-Min","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Keuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Guk","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangsoo","family":"Jang","sequence":"additional","affiliation":[{"name":"CHA University College of Medicine, Seongnam, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong-Ki","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"24","key":"hoi240064r1","doi-asserted-by":"publisher","first-page":"e285","DOI":"10.1016\/j.jacc.2018.11.003","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines.","volume":"73","author":"Grundy","year":"2019","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"hoi240064r2","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidemias: lipid modification to reduce cardiovascular risk.","volume":"41","author":"Mach","year":"2020","journal-title":"Eur Heart J"},{"issue":"15","key":"hoi240064r3","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1056\/NEJMoa040583","article-title":"Intensive vs moderate lipid lowering with statins after acute coronary syndromes.","volume":"350","author":"Cannon","year":"2004","journal-title":"N Engl J Med"},{"issue":"14","key":"hoi240064r4","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1056\/NEJMoa050461","article-title":"Intensive lipid lowering with atorvastatin in patients with stable coronary disease.","volume":"352","author":"LaRosa","year":"2005","journal-title":"N Engl J Med"},{"issue":"19","key":"hoi240064r5","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1001\/jama.294.19.2437","article-title":"High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.","volume":"294","author":"Pedersen","year":"2005","journal-title":"JAMA"},{"issue":"3","key":"hoi240064r6","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.jacc.2006.04.070","article-title":"Meta-analysis of cardiovascular outcomes trials comparing intensive vs moderate statin therapy.","volume":"48","author":"Cannon","year":"2006","journal-title":"J Am Coll Cardiol"},{"issue":"9753","key":"hoi240064r7","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170?000 participants in 26 randomised trials.","volume":"376","author":"Baigent","year":"2010","journal-title":"Lancet"},{"issue":"2","key":"hoi240064r8","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jacl.2015.02.003","article-title":"National lipid association recommendations for patient-centered management of dyslipidemia: part 1\u2013full report.","volume":"9","author":"Jacobson","year":"2015","journal-title":"J Clin Lipidol"},{"issue":"11","key":"hoi240064r9","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/j.jacc.2016.12.036","article-title":"Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction.","volume":"69","author":"Serban","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"8","key":"hoi240064r10","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1001\/jamacardio.2017.0911","article-title":"Adherence to high-intensity statins following a myocardial infarction hospitalization among Medicare beneficiaries.","volume":"2","author":"Colantonio","year":"2017","journal-title":"JAMA Cardiol"},{"issue":"34","key":"hoi240064r11","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1093\/eurheartj\/ehac015","article-title":"Prevalence of statin intolerance: a meta-analysis.","volume":"43","author":"Byty\u00e7i","year":"2022","journal-title":"Eur Heart J"},{"key":"hoi240064r12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2024.07.007","article-title":"High-intensity statins vs. moderate-intensity statin-ezetimibe combination therapy: a patient centered approach.","author":"Grant","journal-title":"J Clin Lipidol"},{"issue":"7","key":"hoi240064r13","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1056\/NEJM199908123410707","article-title":"Drug treatment of lipid disorders.","volume":"341","author":"Knopp","year":"1999","journal-title":"N Engl J Med"},{"issue":"25","key":"hoi240064r14","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1056\/NEJMoa1410489","article-title":"Ezetimibe added to statin therapy after acute coronary syndromes.","volume":"372","author":"Cannon","year":"2015","journal-title":"N Engl J Med"},{"issue":"2","key":"hoi240064r15","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.atherosclerosis.2012.02.016","article-title":"Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials.","volume":"223","author":"Morrone","year":"2012","journal-title":"Atherosclerosis"},{"issue":"20","key":"hoi240064r16","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1016\/j.jacc.2016.02.071","article-title":"Statin-associated side effects.","volume":"67","author":"Thompson","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"17","key":"hoi240064r17","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1093\/eurheartj\/ehv043","article-title":"Statin-associated muscle symptoms: impact on statin therapy\u2014European Atherosclerosis Society consensus panel statement on assessment, etiology, and management.","volume":"36","author":"Stroes","year":"2015","journal-title":"Eur Heart J"},{"issue":"27","key":"hoi240064r18","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1093\/eurheartj\/ehy182","article-title":"Adverse effects of statin therapy: perception vs the evidence\u2014focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract.","volume":"39","author":"Mach","year":"2018","journal-title":"Eur Heart J"},{"issue":"9716","key":"hoi240064r19","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S0140-6736(09)61965-6","article-title":"Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials.","volume":"375","author":"Sattar","year":"2010","journal-title":"Lancet"},{"issue":"24","key":"hoi240064r20","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1001\/jama.2011.860","article-title":"Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.","volume":"305","author":"Preiss","year":"2011","journal-title":"JAMA"},{"issue":"10349","key":"hoi240064r21","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/S0140-6736(22)00916-3","article-title":"Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy vs high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomized, open-label, noninferiority trial.","volume":"400","author":"Kim","year":"2022","journal-title":"Lancet"},{"issue":"13","key":"hoi240064r22","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1001\/jama.2023.2487","article-title":"Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial.","volume":"329","author":"Hong","year":"2023","journal-title":"JAMA"},{"issue":"16","key":"hoi240064r23","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1001\/jama.2015.3656","article-title":"Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD statement.","volume":"313","author":"Stewart","year":"2015","journal-title":"JAMA"},{"key":"hoi240064r24","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomized trials.","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"issue":"7","key":"hoi240064r25","doi-asserted-by":"publisher","first-page":"468","DOI":"10.7326\/M13-2526","article-title":"Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review.","volume":"160","author":"Gudzune","year":"2014","journal-title":"Ann Intern Med"},{"issue":"18","key":"hoi240064r26","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and clinical outcomes in patients with cardiovascular disease.","volume":"376","author":"Sabatine","year":"2017","journal-title":"N Engl J Med"},{"issue":"22","key":"hoi240064r27","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome.","volume":"379","author":"Schwartz","year":"2018","journal-title":"N Engl J Med"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2826516\/jamacardiology_lee_2024_oi_240064_1738111892.43775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:01:51Z","timestamp":1739358111000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2826516"}},"subtitle":["A Systematic Review and Individual Patient Data Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2025,2,1]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2024.3911","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2,1]]}}}