Abstract 4365680: Discontinuation of PCSK9 Inhibitor Therapy and Its Impact on Cardiovascular Outcomes in a Japanese Cohort

Abstract

Background: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have been shown to effectively lower low-density lipoprotein cholesterol (LDL-C) and reduce the risk of cardiovascular events. However, despite these benefits, some patients are unable to continue PCSK9 inhibitor therapy due to financial or other non-medical reasons. Clinical evidence regarding outcomes following discontinuation of PCSK9 inhibitors remains limited. Purpose: This study aims to investigate patients who were unable to continue PCSK9 inhibitor therapy, with particular emphasis on those who discontinued treatment due to financial or other non-medical reasons. The primary objective is to evaluate the impact of therapy discontinuation on the incidence of major adverse cardiovascular events (MACE). Methods: This study included 201 Japanese patients with coronary artery disease who received PCSK9 inhibitor therapy between July 2016 and December 2023. Clinical outcomes were compared between patients who continued therapy and those who discontinued. The primary endpoint was MACE, defined as a composite of all-cause mortality, coronary revascularization, target lesion revascularization (TLR), fatal or non-fatal myocardial infarction (MI), and hospitalization for heart failure. Results: Among the 201 patients (median age: 69 years; interquartile range [IQR]: 59–75; 73% male), the median follow-up duration was 4.7 years (IQR: 2.2–6.4). At one year, the median LDL-C was 42 mg/dL, with 82% achieving LDL-C <70 mg/dL. During follow-up, 111 patients (55.2%) continued therapy, while 90 (44.8%) discontinued. Among those who discontinued, 33% cited financial difficulties, 23% clinical stability, and 21% patient preference. Multivariate Cox regression analysis showed that those who discontinued therapy had a significantly higher incidence of MACE compared to those who continued (hazard ratio: 1.76; 95% confidence interval: 1.03–3.02; p=0.039). Conclusions: Discontinuation of PCSK9 inhibitors—particularly for financial or other non-medical reasons—is associated with an increased risk of MACE. These findings underscore the need for strategies to support long-term adherence and address socioeconomic barriers to therapy continuation. This insight has important implications for clinical decision-making and healthcare policy.