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

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.

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.

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.

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 112mg/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 86mg/dL, increasing goal attainment to 39.1%.

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 ∼11% with ezetimibe, and to ∼40% with ezetimibe+bempedoic acid.