Effectiveness, adherence and safety of evolocumab in a Swiss multicenter prospective observational study

Abstract

Abstract Background/Introduction Achievement of low LDL-C-levels and adherence to lipid lowering therapy (LLT) is essential to prevent recurrent cardiovascular (CV) events. However, most patients (pts) with acute coronary syndromes don't maintain LDL-C levels within guideline recommendations beyond 1 year. Practical solutions to increase long-term adherence to LLT are needed. Purpose To describe pts receiving evolocumab (evo) and drug adherence in a real-world clinical setting. Methods We enrolled adults ≥18 years with confirmed atherosclerotic cardiovascular disease (ASCVD) or at high CV risk, and elevated LDL-C levels despite maximally tolerated statin therapy. Physicians in clinical practice prescribed evo according to Swiss reimbursement limitations. At baseline (BL), all pts used evo; some were already on PCSK9i treatment (PCSK9i pre-treated), others were newly initiated on evo (PCSK9i naïve); planned follow-up was 12 months. The web-based mHealthAlert system was offered to support pts' therapy management. The primary outcome was cholesterol levels at BL and after 3, 6 and 12 months of evo therapy. Results All 100 enrolled pts completed 12 months follow-up. For BL characteristics see Table. 81% had a history of at least one CV event and 55% had ≥2 previous CV events; 3% had familial hypercholesterolemia. At BL, 71% had a history of statin-related muscle symptoms, 44% had documented statin use, 65% were PCSK9i pre-treated and 35% were PCSK9i naïve; overall median LDL-C was 1.9 mmol/L. In PCSK9i naive pts, median LDL-C at enrolment was 3.5 mmol/L and fell by a mean of 2.1 mmol/L (60% reduction) within 3 months of evo initiation; this reduction was maintained over 12 months. The 2016 ESC/EAS LDL-C goals (<1.8 mmol/L) were attained at least once over 12 months by 74% of pts while 69% attained the 2019 goals (<1.4 mmol/L). In PCSK9i pre-treated pts, LDL-C remained stable during evo treatment; 79% and 74% attained the 2016 and 2019 goals, respectively, at least once over 12 months. Goal attainment was higher in pts receiving combination therapy of evo ± statin ± ezetimibe (Figure). Overall, 89% of pts self-reported full adherence to evo. Adverse events were reported in 30% of pts, two events in one pt were considered serious (increased blood creatine phosphokinase and myopathy) and three pts discontinued evo due to adverse events. Conclusion In Swiss clinical practice, evo was mainly used in high CV risk pts with statin-related muscle symptoms and severe CV disease. In this population, adherence to evo and low LDL-C levels were maintained over one-year. Among pts using evo either in mono- or combination therapy, the majority attained guideline recommended LDL-C levels. However, goal attainment was higher in pts using evo in combination with other LLT, especially with regards to LDL-C <1.4 mmol/L. Effectiveness and safety of evo in real-world clinical practice was comparable to that found in randomized, controlled clinical trials. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Study 20150245 was funded by Amgen Switzerland AG