Background: Despite the intensive approach recommended by the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines, low-density lipoprotein cholesterol (LDL-C) target attainment (<55 mg/dL or <40 mg/dL for patients with recurrent events within 2 years) in atherosclerotic cardiovascular disease (ASCVD) patients remains low, with clinical inertia and lack of lipid-lowering therapy (LLT) optimization as major barriers.
Methods: We analyzed real-world LLT patterns in the ITACARE-P registry, enrolling 1909 Italian ASCVD patients referred to cardiovascular rehabilitation or secondary prevention programs. Baseline LLT and LDL-C levels were recorded. For patients not at LDL-C target, a Monte Carlo simulation with 10,000 iterations was performed using efficacy data from pivotal randomized trials to model sequential addition of ezetimibe, bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and inclisiran to estimate potential LDL-C goal attainment rates.
Results: Among 1909 patients (mean age 66 ± 10 years, 26% women), 41.3% were at LDL-C target. Most (90%) were on statins, predominantly at moderate or high intensity, whereas only 3% were untreated. Among patients not at LDL-C target, the Monte Carlo simulation predicted a stepwise increase in goal attainment from 43% to 50% after ezetimibe, 63% after bempedoic acid, 95% after PCSK9 inhibitors, and 90% after inclisiran. A baseline percentage distance of 23.66% from the LDL-C target was identified as a threshold beyond which the addition of bempedoic acid alone was rarely sufficient (<5% success), supporting direct escalation to injectables.
Conclusion: A structured, guideline-based intensification strategy in secondary prevention could close the treatment gap and enable near-universal LDL-C target achievement, supporting early implementation of combination therapy.
Keywords: Clinical inertia; Lipid-lowering therapy; Lipids; Monte Carlo simulation; Secondary prevention.
Copyright © 2025. Published by Elsevier Inc.