From Clinical Inertia to Therapeutic Optimization in Patients with Atherosclerotic Cardiovascular Disease: A Monte Carlo Simulation within the ITACARE-P Registry

Background Despite the intensive approach recommended by the 2019 ESC/EAS guidelines, 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, 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. Conclusions 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.