https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Jena Klinik für Innere Medizin I - Kardiologie Jena, Deutschland; 2Universitätsklinikum Leipzig Klinik und Poliklinik für Kardiologie Leipzig, Deutschland; 3Institute of Nutritional Sciences, Friedrich Schiller University Jena Jena, Deutschland; 4Novartis Pharma GmbH Nürnberg, Deutschland; 5Nephrologisches Zentrum Göttingen GbR Göttingen, Deutschland
The role of lipid management as a crucial component in cardiovascular risk reduction is well established. However, poor adherence to guideline recommended therapy and poor goal achievement in (very) high risk Atherosclerotic Cardiovascular Disease (ASCVD) patients is observed.
Methods
In this non-interventional prospective study, data from ASCVD patients at 130 study sites in Germany are collected. The primary objective is to provide descriptive data on patient characteristics in terms of demographics, medical history, comorbidity burden and previous CV events. Patients are enrolled at the time of lipid lowering therapy (LLT) escalation and followed-up for 21 months. All data are recorded as available from clinical routine. Patients are enrolled into one of four treatment arms. In cohort A, patients initiate one or more oral LLTs (oLLT) on top of maximum tolerated statin. Patients in cohort B initiate Inclisiran according to reimbursement criteria, patients in cohort C initiate Inclisiran on top of lipid apheresis. Cohort B is subdivided into a Proprotein-Convertase-Subtilisin-Kexin-Typ-9 inhibitor (PCSK9i) naïve cohort (B1) and a cohort with prior use of PCSK9i (B2). In this interim analysis (IA), the secondary endpoints effectiveness of LDL-C lowering, LDL-C goal achievement and adherence to LLT are analyzed.
Results
At the time of this IA, baseline- and 3 months data were available for 561 patients in cohort A and for 576 patients in cohort B. Cohort C data were not representative (n=4). Patients initiating additional oLLTs (A) or Inclisiran (B) represent distinct patient populations regarding age, gender, medical history and intensity of background LLT (Table 1). Patients in cohort A represent a very high ASCVD risk population that is intensively treated with oLLTs, with 83% on statins + ezetimibe and/or bempedoic acid (BPA). Median (Q1; Q3) baseline LDL-C level is 84.9 (73.0; 104.3) mg/dL. Patients in cohort B escalated therapy with inclisiran while they could not achieve LLT goals with oLLTs, with 44% receiving any statin, 46% ezetimibe and 33% dual oLLT based on statins. Median baseline LDL-C level is 105 (81.9; 143.0) mg/dL.
Therapy escalation with one or more oLLTs shows a median LDL-C reduction of -36.4% (-47.4; -20.8) at the 3 months visit. 58.3% of oLLT patients do not reach their LDL-C goal of <55 mg/dL.
In PCSK9i naïve patients (n=511, cohort B1) Inclisiran reduces LDL-C by -42.4% (-55.6; -24.2). Patients on intensive combination therapy (n=158) show most pronounced improvement (median -51.5% (-60.5; -40.6)). Compatibly, 58.2% of cohort B1 patients receiving intensive background LLT reach their LDL-C goal, while goal achievement is significantly lower in the overall cohort (36.5%).
Patients initiating Inclisiran after discontinuation of previous PCSK9i (n= 65) show a similar LDL-C value at the 3 months visit compared to baseline (-6.8% (-37.0; 30.0)). 6.3% of these patients are below the target LDL-C of 55 mg/dL at this time.
At 15 months (n=278), the overall adherence to Inclisiran is 91% and the persistence is 94,5%, while adherence to oLLT (n=408) is 67% and persistence is 70%.
Conclusion
58.3% of very high risk ASCVD patients did not achieve their LDL-C goal with oLLT escalation in clinical practice and need further LLT escalation. After the initial dose, Inclisiran lowered LDL-C by 42% in patients not reaching target with max. tolerated oLLT. High therapy adherence and persistence was observed.