Treatment with PCSK9 monoclonal antibodies is associated with discontinuation of oral lipid lowering therapy.

Aims: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) are recommended for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe. We studied persistence and adherence to 1) PCSK9 mAbs and 2) statins and ezetimibe in a nationwide cohort of incident PCSK9 mAb users.

Methods and results: Information on all PCSK9 mAb users ≤80 years from 2015 through 2023 were extracted from the Norwegian Drug Registry. Discontinuation was defined as a gap in treatment ≥180 days and ≥90 days. Adherence was measured as the proportion of days covered (PDC) during the initial year of PCSK9 mAb therapy. We analyzed adherence of statins and ezetimibe before and after PCSK9 mAb initiation. Of 4,784 patients initiating PCSK9 mAbs, median age was 63 years, 41% were female, 61% had atherosclerotic disease, and 34% had familial hypercholesterolemia. Within three years after initiation, 17% experienced a PCSK9 mAb treatment gap exceeding 180 days. In the 12-month period preceding PCSK9 mAb initiation, 74% dispensed statins whereas 67% dispensed ezetimibe. These numbers were reduced to 35% for statins and 42% for ezetimibe during the 12-month period after PCSK9 mAb initiation. Atherosclerotic disease, using ≥3 statins previously, and older age were significantly associated with discontinuation of statins and ezetimibe.

Conclusion: In this high-risk cohort of incident PCSK9 mAb users, more than 1 out of 2 stopped taking statin treatment whereas 40% discontinued ezetimibe. There is a major potential for improving adherence to oral LLD treatment following initiation of PCSK9 mAb.