The PENELOPE-CTRL study showed that a protocol-led LDL‑C lowering strategy significantly improved LDL‑C goal attainment compared to real-world controls in the Netherlands. High LDL‑C target attainment with the protocol (86% initially and 64% at one year post-MI) contrasted with only 55% in routine care.

Poor LDL‑C goal attainment and infrequent LDL‑C measurements in CTRL aligns with findings from recent European studies (DA VINCI, EUROASPIRE V, SANTORINI, INTERASPIRE), highlighting a critical gap in LDL‑C monitoring in current real-world practice. A sustained LDL‑C reduction of 0.3 mmol/L after one year, relative to real-world controls, translates into an estimated 3% additional annual reduction in cardiovascular event risk [1, 8]. Continued adherence to LDL‑C lowering may amplify risk reduction over time.

Strengths of this study include the contemporary, geographically representative nationwide cohorts. However, the retrospective design of PENELOPE-CTRL may introduce bias, for example, due to the observed lack of LDL‑C monitoring in routine care. Sensitivity analysis using best- and worst-case imputation for missing LDL‑C data showed superiority of PENELOPE ≤ 70 over CTRL in both scenarios (p < 0.001).

In conclusion, the PENELOPE-CTRL study illustrates that a protocol-led LDL‑C lowering strategy significantly improves both timely and overall LDL‑C goal attainment compared to real-world controls. A graphical summary (in Dutch) of the study’s key methods, results, and implications has been developed for use in clinical settings to raise awareness and support the implementation of structured LDL‑C management in patients after myocardial infarction to optimise clinical outcomes (Electronic Supplementary Material, Fig. S4).

Distribution and median of LDL‑C levels with a short protocol-led LDL‑C lowering strategy (PENELOPE ≤ 70) versus real-world controls (CTRL) in patients after myocardial infarction. At baseline (hospitalisation for myocardial infarction), within the study period of 6 months and after approximately one year