PCSK9 inhibition in clinical practice: Treatment patterns and attainment of lipid goals in a large health maintenance organization

Background: Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C), improving cardiovascular outcomes in clinical trials when added to statin therapy. Objectives: As real-world evidence is lacking, we aimed to evaluate treatment and adherence patterns using PCSK9i in clinical practice. Methods: We investigated 1600 patients initiating PCSK9i between January 2016 and December 2019 in a large health maintenance organization. Treatment discontinuation was defined as a gap ≥60 days between last days' supply of one prescription and the start of the next. Re-initiation rates as well as proportion of days covered (PDC) over 1-year period and attainment of lipid goals under PCSK9i, were analyzed. Results: Evolocumab 140 mg was initiated by 50.7%, alirocumab 75 mg by 29.5% and 150 mg by 19.8%. Cumulative discontinuation rates were 28.1% after 6-months and 49.9% after 3-years. Overall, 58% of the patients that discontinued therapy have re-initiated PCSK9i (31% after 3-months from discontinuation). Mean PDC over 1-year of therapy was 56% ± 29, with PDC ≥80% evident in 29%. Of those with established cardiovascular disease (n = 991), 55% achieved LDL-C<70 mg/dL and 38% LDL-C<55 mg/dL. Attainment rates were lower in patients with PDC<80%, baseline LDL-C>190 mg/dL and in those not treated with concurrent statin therapy. Conclusions: In real-world practice of patients treated by PCSK9i, high proportion of early treatment discontinuation was evident, with non-negligible re-initiation rates but overall low medication coverage over time. This have contributed to sub-optimal attainment of LDL-C treatment goals, particularly observed in patients with severe hypercholesterolemia, inadequate drug adherence, and those using PCSK9i as monotherapy.