Adherence to PCSK9 Inhibitors in Clinical Practice: Systematic Review and Meta-Analysis of Observational Studies

Medication nonadherence is a barrier to the long-term effectiveness of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in clinical practice.

The aim of the study was to determine the prevalence of adherence to PCSK9 inhibitors in real-world practice across all adherence phases.

MEDLINE, EMBASE, PsycINFO, CINAHL Plus, and medRxiv were searched from inception to August 2, 2024. Observational studies reporting at least 1 quantitative adherence measure for alirocumab, evolocumab, or inclisiran were included. Study quality was assessed with the Joanna Briggs Institute checklist for prevalence studies. Data were pooled using random-effects meta-analysis with multilevel models to account for measurements at multiple time points. Measures of medication adherence were categorized into initiation, implementation (medication possession ratio [MPR] and proportion of days covered), and persistence (persistence and discontinuation) phases.

We included 94 studies in the systematic review, with 56 studies (n = 75,902), primarily evaluating alirocumab and evolocumab, contributing to a quantitative synthesis. Initiation was high at 91.7% (95% CI: 83.6-96.0; I² = 94.2%). MPR was 95.1% (95% CI: 92.7-97.5; I² = 98.4%) at 6 months and 86.5% (95% CI: 80.2-92.9; I² = 99.7%) at 24 months. The 12-month proportion of days covered was 69.7% (95% CI: 55.9-83.5; I² = 99.8%). At 12 months, persistence was 81.8% (95% CI: 68.2-90.4; I² = 99.1%), and the discontinuation rate was 12.1% (95% CI: 7.4-19.0; I² = 98.9%). Multilevel meta-analyses demonstrated declines in MPR and persistence beyond 12 months of follow-up.

Although patients frequently initiate PCSK9 inhibitors, both implementation and persistence diminish over time, underscoring the need for strategies that sustain medication adherence in clinical practice. With limited evidence beyond 24 months of follow-up and for inclisiran, additional long-term observational studies are essential to guide real-world management.