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.
From clinical inertia to therapeutic optimization in patients with atherosclerotic cardiovascular disease: A Monte Carlo simulation within the ITACARE-P registry / Faggiano, Andrea; Maloberti, Alessandro; Ambrosetti, Marco; Giallauria, Francesco; Mureddu, Gianfrancesco; Venturini, Elio; Ruzzolini, Matteo; Maranta, Francesco; Vatri, Marco; Zadre, Lana; Carugo, Stefano; Ruscica, Massimiliano; Fattirolli, Francesco; Faggiano, Pompilio. - In: JOURNAL OF CLINICAL LIPIDOLOGY. - ISSN 1933-2874. - 20:1(2026), pp. 21-30. [10.1016/j.jacl.2025.11.010]
From clinical inertia to therapeutic optimization in patients with atherosclerotic cardiovascular disease: A Monte Carlo simulation within the ITACARE-P registry
Giallauria, Francesco;
2026
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
