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.