Evolocumab 140mg/1ml solution for injection pre-filled disposable devices

BackgroundHypercholesterolemia is a major risk factor for cardiovascular disorders. Evolocumab is efficacious and safe for the management of low-density lipoprotein cholesterol (LDL-C); however, evidence supporting the utility of evolocumab in Japanese patients is lacking. To fill this evidence gap, we conducted this systematic review and meta-analysis.Methods and resultsPubMed, EMBASE, Web of Science, and the Cochrane Library from inception to October 2023 were searched for relevant publications. The primary outcomes were LDL-C levels and coronary artery plaque regression or stabilization. The secondary outcome was the incidence of adverse events. Nine studies were included: 6 randomized control trials (RCTs) and 3 cohort studies. The meta-analysis showed that evolocumab significantly reduced LDL-C levels in RCTs in the short (≤1 month), medium (≤3 months), and long (1 year) term, with a mean difference (MD) relative to placebo/standard of care (SOC) of -52.06% (95% confidence interval [CI] -59.32%, -44.79%), -69.12% (95% CI -71.45%, -66.79%), and -78.08% (95% CI -82.98%, -73.18%), respectively, and in the mid- to long (≤6 months) term in a cohort study, with an MD of -57.81% (95% CI -74.37%, -41.25%). Evolocumab also increased fibrous cap thickness and reduced macrophage grade. Adverse events were rare across included studies.ConclusionsEvolocumab seems to be effective and safe in reducing the LDL-C levels and leading to plaque regression/stabilization in Japanese patients.

Abstract licence: CC BY-NC-ND

BackgroundMedication nonadherence is a barrier to the long-term effectiveness of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in clinical practice.ObjectivesThe aim of the study was to determine the prevalence of adherence to PCSK9 inhibitors in real-world practice across all adherence phases.MethodsMEDLINE, 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.ResultsWe 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.ConclusionsAlthough 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.

Abstract licence: CC BY