Barak Zafrir1, Aya Egbaria2, Nili Stein3, Avishay Elis4, Walid Saliba5. 1. The Department of Cardiology, Lady Davis Carmel Medical Center, Haifa, Israel; The Faculty of Medicine, Technion, Israel Institute of Medicine, Haifa, Israel. Electronic address: barakzmd@gmail.com. 2. The Faculty of Medicine, Technion, Israel Institute of Medicine, Haifa, Israel. 3. The Statistical Unit, Lady Davis Carmel Medical Center, Haifa, Israel. 4. The Department of Medicine, Beilinson Hospital, Rabin Medical Center, PetachTikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. The Faculty of Medicine, Technion, Israel Institute of Medicine, Haifa, Israel; The Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
Abstract
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.
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.
Authors: Kiran Musunuru; Alexandra C Chadwick; Taiji Mizoguchi; Sara P Garcia; Jamie E DeNizio; Caroline W Reiss; Kui Wang; Sowmya Iyer; Chaitali Dutta; Victoria Clendaniel; Michael Amaonye; Aaron Beach; Kathleen Berth; Souvik Biswas; Maurine C Braun; Huei-Mei Chen; Thomas V Colace; John D Ganey; Soumyashree A Gangopadhyay; Ryan Garrity; Lisa N Kasiewicz; Jennifer Lavoie; James A Madsen; Yuri Matsumoto; Anne Marie Mazzola; Yusuf S Nasrullah; Joseph Nneji; Huilan Ren; Athul Sanjeev; Madeleine Shay; Mary R Stahley; Steven H Y Fan; Ying K Tam; Nicole M Gaudelli; Giuseppe Ciaramella; Leslie E Stolz; Padma Malyala; Christopher J Cheng; Kallanthottathil G Rajeev; Ellen Rohde; Andrew M Bellinger; Sekar Kathiresan Journal: Nature Date: 2021-05-19 Impact factor: 69.504