The effect of implementing a guideline-based approach to achieve target LDL-C levels in very high risk patients. The PENELOPE study one year follow-up results

Abstract

Abstract Background/introduction Hyperlipidemia is a major modifiable risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease (1,2). The PENELOPE study implemented an ESC-guideline-based, stepwise strategy of lipid-lowering therapy (LLT) to achieve target LDL-C levels in very high-risk patients, with a mean duration of 61 days. Purpose This paper demonstrates the legacy effect after one year. Methods Nine hundred and ninety-nine (999) patients with a myocardial infarction and a history of atherosclerotic cardiovascular disease and/or diabetes mellitus were included in PENELOPE for stepwise intensified LLT (high intensity statin (HIST) monotherapy, HIST + ezetimibe, HIST + ezetimibe + PCSK9i) until reaching target LDL-C level (≤1.8mmol/L). The primary objective was to assess the prevalence of maintained LDL-C ≤1.8 mmol/L and therapy-adherence after one year. Results For the one year follow up visit, 738 patients (73%) were available. Thirty patients had died, 45 were lost to follow up and from 178 patients no signed informed reconsent was obtained. The per protocol cohort included six hundred and seventy-one (671) patients. In this cohort, a non-participation bias cannot be excluded. After one year, in four-hundred forty-nine (449) patients target LDL-C level (66,9%) was maintained. Mean LDL-C level after one year was 1.67 mmol/L and the adherence rate to LLT was 94,5%. The major treatment regimens were statin monotherapy (61,7%), statin + ezetimibe (28,3%) and PCK9i + ezetimibe (+ statin) (5,8%). Maintained target (LDL-C ≤1.8mmol/L) was 64%, 77% and 82%, respectively. The large percentage loss of patients on target after one year could be explained by the cut-off at 1.8 mmol/L (only 0.28 mmol/L increase in mean LDL-C level), the short-term effect of heart rehabilitation and a treatment change in 20,4% of patients. Therapy adherence was high and did not differ between treatment regimen. Conclusion Using an ESC-guideline-based flowchart with quick, stepwise intensification of LLT leads to a 99% success rate (LDL-C ≤1.8mmol/L) within 3 months and 67% after one year. The mean LDL-C level increases with 0.28 mmol/L.