{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:16:02Z","timestamp":1792145762517,"version":"4.4.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite three decades of using statin therapy, 20 years of experience with ezetimbe, and availability of innovative non-statin lipid lowering therapies (LLT), there are still about 70% patients over the low-density lipoprotein cholesterol (LDL-C) goal, with every 5th to 6th being over the target from the group of very high and extremely high cardiovascular disease (CVD) risk patients. Adding another even every 5th patient at very high CVD risk without any LLT makes this situation highly frustrating, especially lipid disorders are the most common CVD risk factor with the prevalence of over 60%, with the worst awareness within all cardiovascular risk factors (only about 15% people knows their LDL-C level). To answer this since 2021, there is an approach to apply upfront (immediate) lipid-lowering combination therapy of statin and ezetimibe in very high and extremely high-risk patients to be on the LDL-C target as low as possible, but especially as early as possible, enabling to introduce the third line therapy (i.e. bempedoic acid and\/or PCSK9 targeted therapy) already after 4\u20136 weeks. This review discusses the current stage of knowledge and recent data on the group of patients that might benefit the most from the upfront combination LLT, when it should be optimally implemented, and the recent data on its role on LDL-C reduction, cardiovascular and mortality outcomes as well as safety issues.<\/jats:p>","DOI":"10.1093\/cvr\/cvaf045","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:01:36Z","timestamp":1742274096000},"page":"851-859","source":"Crossref","is-referenced-by-count":28,"title":["Upfront lipid-lowering combination therapy in high cardiovascular risk patients: a route to effective atherosclerotic cardiovascular disease prevention"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-6874","authenticated-orcid":false,"given":"Maciej","family":"Banach","sequence":"first","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL) , Rzgowska 281\/289, Lodz 93-228 ,","place":["Poland"]},{"name":"Faculty of Medicine, the John Paul II Catholic University of Lublin , Lublin ,","place":["Poland"]},{"name":"Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother\u2019s Memorial Hospital Research Institute (PMMHRI) , Lodz ,","place":["Poland"]},{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine , Baltimore, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanis\u0142aw","family":"Surma","sequence":"additional","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL) , Rzgowska 281\/289, Lodz 93-228 ,","place":["Poland"]},{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia , Katowice 40-752 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz J","family":"Guzik","sequence":"additional","affiliation":[{"name":"Center for Medical Genomics OMICRON, Jagiellonian University Medical College , Krakow ,","place":["Poland"]},{"name":"Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College , Krakow ,","place":["Poland"]},{"name":"BHF Centre for Research Excellence, Centre for Cardiovascular Sciences, The University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E","family":"Penson","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy & Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University , Liverpool ,","place":["UK"]},{"name":"Centre of Pharmacy Innovation, Liverpool John Moores University , Liverpool ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Blaha","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine , Baltimore, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto J","family":"Pinto","sequence":"additional","affiliation":[{"name":"Structural and Coronary Heart Disease Unit, Cardiovascular Center of the University of Lisbon, Faculdade de Medicina, Universidade de Lisboa , Lisboa ,","place":["Portugal"]},{"name":"Servi\u00e7o de Cardiologia, Departamento de Cora\u00e7\u00e3o e Vasos, CHULN Hospital de Santa Maria , Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence S","family":"Sperling","sequence":"additional","affiliation":[{"name":"Emory Center for Heart Disease Prevention, Emory University School of Medicine , Atlanta, GA ,","place":["USA"]},{"name":"Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine , Atlanta, GA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"2025061210313635600_cvaf045-B1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/eurjpc\/zwab213","article-title":"Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990\u20132019","volume":"29","author":"Safiri","year":"2022","journal-title":"Eur J Prev Cardiol"},{"key":"2025061210313635600_cvaf045-B2","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2025061210313635600_cvaf045-B3","first-page":"1602","article-title":"2023: the year in cardiovascular disease\u2014the year of new and prospective lipid lowering therapies. 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