Therapeutic Inertia in Lipid-Lowering Treatment: A Narrative Review

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 "phenotypes" 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 "avoidable atherosclerotic burden", 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 'phenotypes' and the concept of 'avoidable atherosclerotic burden' as a framework to understand and address this gap.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2026-01-29
DOI
https://doi.org/10.3390/jcm15031075
Primary Topic
Lipoproteins and Cardiovascular Health
Type
article
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article

Therapeutic Inertia in Lipid-Lowering Treatment: A Narrative Review

Francesco Fattirolli, Andrea Faggiano, Elisabetta Angelino, Marco Vatri et al.
Journal of Clinical Medicine
Lipoproteins and Cardiovascular Health
article

Therapeutic Inertia in Lipid-Lowering Treatment: A Narrative Review

Francesco Fattirolli, Andrea Faggiano, Elisabetta Angelino, Marco Vatri, Marco Ambrosetti, Pompilio Massimo Faggiano
article en

Abstract

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 "phenotypes" 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 "avoidable atherosclerotic burden", 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 'phenotypes' and the concept of 'avoidable atherosclerotic burden' as a framework to understand and address this gap.

Journal of Clinical MedicineVol. 15(3)
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Istituti Clinici Scientifici Maugeri (IT), Ospedale Santa Maria (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), University of Florence (IT)
Openalex Percentile: Top 73%
Lipoproteins and Cardiovascular Health
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