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.
Authors
- Francesco Fattirolli (ORCID: https://orcid.org/0000-0002-1345-0284)
- Andrea Faggiano (ORCID: https://orcid.org/0000-0002-3247-3203)
- Elisabetta Angelino (ORCID: https://orcid.org/0000-0003-2300-6985)
- Marco Vatri (ORCID: https://orcid.org/0009-0000-3423-062X)
- Marco Ambrosetti
- Pompilio Massimo Faggiano
Institutions
- 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)
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
- Field-Weighted Citation Impact
- 0.00