{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:10:15Z","timestamp":1788898215189,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Therapeutic inertia in lipid-lowering treatment remains a striking paradox of modern cardiovascular medicine: at a time when the causal role of LDL-cholesterol in atherosclerotic disease is unequivocal and potent therapies are widely available, a substantial proportion of high- and very-high-risk patients still fail to receive timely treatment intensification. Contemporary European and international data consistently show fewer than one in three patients in secondary prevention achieve guideline-recommended LDL-C targets, revealing a persistent and unacceptable gap between scientific evidence and clinical reality. This narrative review examines therapeutic inertia as a key explanatory framework for this gap, describing its epidemiology, mechanisms, and clinical consequences in secondary cardiovascular prevention. We summarize the main physician-, patient-, and system-level determinants and propose recurrent clinician \u201cphenotypes\u201d of inertia that may help explain why opportunities are missed even in the highest-risk patients. The consequences are profound: therapeutic inertia contributes to what we propose as the conceptual framework of an \u201cavoidable atherosclerotic burden\u201d, the cumulative vascular injury that accrues each period in which LDL-C remains above target, translating into higher rates of avoidable cardiovascular events, and increased healthcare costs. Emerging strategies such as upfront combination therapy, decision-support systems, structured lipid pathways, and the integration of artificial intelligence offer practical tools to shift lipid management from reactive to proactive care. Overcoming therapeutic inertia is therefore not merely a matter of improving process metrics, but a clinical and ethical imperative. Closing the gap between evidence and practice requires transforming optimal lipid management from an exception into a system-level default, ensuring that every patient receives the full benefit of therapies proven to save lives. This work proposes a novel characterization of clinician \u2018phenotypes\u2019 and the concept of \u2018avoidable atherosclerotic burden\u2019 as a framework to understand and address this gap.<\/jats:p>","DOI":"10.3390\/jcm15031075","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:49:07Z","timestamp":1769690947000},"page":"1075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic Inertia in Lipid-Lowering Treatment: A Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3423-062X","authenticated-orcid":false,"given":"Marco","family":"Vatri","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Sperimentale e Clinica, Universit\u00e0 di Firenze, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3247-3203","authenticated-orcid":false,"given":"Andrea","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Dipartimento Cardio-Toracico-Vascolare, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Angelino","sequence":"additional","affiliation":[{"name":"Laboratorio dell\u2019Esercizio e dei Segnali Cardiorespiratori, Istituti Clinici Scientifici Maugeri IRCCS, 28013 Veruno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-4565","authenticated-orcid":false,"given":"Marco","family":"Ambrosetti","sequence":"additional","affiliation":[{"name":"U.O.C. Riabilitazione Cardiologica, ASST di Crema, Ospedale Santa Maria, 26027 Rivolta d\u2019Adda, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-6908","authenticated-orcid":false,"given":"Pompilio Massimo","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Cardiologia, Dipartimento Cardiovascolare, Fondazione Poliambulanza Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-0284","authenticated-orcid":false,"given":"Francesco","family":"Fattirolli","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale e Clinica, Universit\u00e0 di Firenze, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1093\/eurjpc\/zwaf288","article-title":"Despite More Aggressive Lipid-Lowering Guidelines Worldwide, the Majority of High-Risk Patients Remain Undertreated","volume":"32","author":"Toth","year":"2025","journal-title":"Eur. 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