2026 · ARCHIVES OF CARDIOVASCULAR DISEASES

Optimizing oral low-density lipoprotein cholesterol-lowering therapy in statin-intolerant patients: A simulation study in France

Schiele, Francois, Farnier, Michel, Borsik, Benedicte

Journal
ARCHIVES OF CARDIOVASCULAR DISEASES
Année
2026
Volume
119
Numéro
3
Pages
192-200
Mois
MAR
DOI
10.1016/j.acvd.2025.08.008

Abstract

Background: Lipid-lowering therapies effectively reduce low-density lipoprotein cholesterol concentrations and the risk of cardiovascular events, but barriers such as statin intolerance, non-adherence and discontinuation can leave patients at risk. Aim: This study characterized statin-intolerant patients in France, and modelled the low-density lipoprotein cholesterol-lowering effects of ezetimibe and bempedoic acid for those at elevated cardiovascular risk. Methods: Patients were identified based on IQVIA electronic medical records from 1200 general practitioners (September 2022 to August 2023), and this sample was extrapolated to represent the French population. Patients were identified as at high or very high probability of statin intolerance based on statin-associated muscle symptoms, statin downtitration or intermittent dosing/statin switch. The low-density lipoprotein cholesterol-lowering effect of stepwise addition of ezetimibe and bempedoic acid was modelled using a Monte Carlo simulation. Results: Among patients at high or very high cardiovascular risk, 478,370 had statin intolerance: 54.5% at high and 45.5% at very high probability. Overall, 3.6% of patients were not receiving lipid-lowering therapy; most were receiving monotherapy with statins (46.8%) or ezetimibe (24.6%), and 24.4% were receiving a statin +ezetimibe. Of 179,458 patients with a low-density lipoprotein cholesterol result within 12 months and who received lipid-lowering therapy within 3.5 months of the index date, 90% (n = 160,633) were not at low-density lipoprotein cholesterol goal at simulation baseline. In this population, adding ezetimibe reduced the mean low-density lipoprotein cholesterol concentration from 127 to 112 mg/dL, with a 10.7% increase in goal attainment. Adding bempedoic acid in patients not at goal after ezetimibe further decreased the low-density lipoprotein cholesterol concentration to 86 mg/dL, increasing goal attainment to 39.1%. Conclusions: Most (90%) statin-intolerant patients in France do not meet low-density lipoprotein cholesterol goals, emphasizing the need for therapeutic strategies and evidence-based guidelines to improve outcomes. This simulation suggests that treatment escalation could increase low-density lipoprotein cholesterol goal attainment to similar to 11% with ezetimibe, and to similar to 40% with ezetimibe +bempedoic acid. (c) 2025 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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