Comparing protocol-led lipid management with daily practice in post-myocardial infarction patients

Introduction The PENELOPE study demonstrated the effectiveness of a 3-step, guideline-based lipid management strategy in achieving low-density lipoprotein-cholesterol (LDL-C) goals in very high-risk atherosclerotic cardiovascular disease (ASCVD) patients. However, this was an uncontrolled observation. The PENELOPE-CTRL study therefore retrospectively compared these findings with real-world lipid management practices in the Netherlands. Methods Between 2019 and 2020, the PENELOPE study enrolled 663 patients <70 years with acute coronary syndrome with a history of diabetes mellitus or ASCVD, to investigate a 3-step lipid lowering treatment (LLT) intensification (statins, +ezetimibe, +PCSK9 inhibitors) to achieve LDL-c ≤1.8 mmol/L. For the comparative analysis, the real-life PENELOPE-CTRL (N=827) comprised a comparable cohort of retrospectively included patients with similar inclusion criteria. The primary outcome was the proportion of patients reaching an LDL-C target of ≤1.8 mmol/L within six months and at one-year follow-up. Results Baseline lipid management was similar in both cohorts, with 33% in PENELOPE vs. 32% in PENELOPE-CTRL on target. The stepwise protocol outperformed real-life practice, with 86% (95% CI 83%-88%) vs. 55% (95% CI 51%-58%) reaching an LDL-c ≤1.8mmol/L within the study period (p<0.001). After one year, this effect was attenuated but remained statistically significant in favour of the intervention (LDL on target 64% (95% CI 60%-68%) vs. 55% (95% CI 50%-60%), p=0.008).(Figure 1). Conclusion Using a stepwise lipid protocol significantly improves the proportion of patients reaching LDL-C target in very high-risk post-acute coronary syndrome patients compared to real-life controls. These effects were attenuated after one year follow-up, suggesting the need for long-term follow-up to lower lipid-driven residual risk. Protocol-led vs. daily LDL-C management.