Federica Fogacci1, Giuseppe Danilo Norata2, Peter P Toth3,4, Marcello Arca5, Arrigo F G Cicero6,7. 1. Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy. 2. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. 3. The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA. 4. Preventive Cardiology, CGH Medical Center, Sterling, IL, USA. 5. Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. 6. Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy. arrigo.cicero@unibo.it. 7. Medical and Surgical Sciences Department, Sant'Orsola-Malpighi University Hospital, Via Albertoni, 15, 40138, Bologna, Italy. arrigo.cicero@unibo.it.
Abstract
PURPOSE OF REVIEW: To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies. RECENT FINDINGS: The meta-analysis of three clinical studies comprising 11 arms (N = l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = - 67.90%, 95%CI = - 85.32, - 50.48, P < 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P < 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = - 72.90%, 95%CI = - 82.73, - 63.07, P < 0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P = 0.007], Apo B-48 [MD = - 64.63, 95%CI = - 105.37, - 23.88, P = 0.002], ApoCIII [MD = - 74.83%, 95%CI = - 85.93, - 63.73, P < 0.001], and VLDL ApoCIII [MD = - 83.69%, 95%CI = - 94.08, - 73.29, P < 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = - 1.31, 95.33, P = 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P < 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P < 0.05) when compared to placebo. Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.
PURPOSE OF REVIEW: To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies. RECENT FINDINGS: The meta-analysis of three clinical studies comprising 11 arms (N = l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = - 67.90%, 95%CI = - 85.32, - 50.48, P < 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P < 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = - 72.90%, 95%CI = - 82.73, - 63.07, P < 0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P = 0.007], Apo B-48 [MD = - 64.63, 95%CI = - 105.37, - 23.88, P = 0.002], ApoCIII [MD = - 74.83%, 95%CI = - 85.93, - 63.73, P < 0.001], and VLDL ApoCIII [MD = - 83.69%, 95%CI = - 94.08, - 73.29, P < 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = - 1.31, 95.33, P = 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P < 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P < 0.05) when compared to placebo. Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.
Authors: Abel A Pavía-López; Marco A Alcocer-Gamba; Edith D Ruiz-Gastelum; José L Mayorga-Butrón; Roopa Mehta; Filiberto A Díaz-Aragón; Jorge A Aldrete-Velasco; Nitzia López-Juárez; Ivette Cruz-Bautista; Adolfo Chávez-Mendoza; Nikos C Secchi-Nicolás; Francisco J Guerrero-Martínez; Jorge E Cossio-Aranda; Victoria Mendoza-Zubieta; Guillermo Fanghänel-Salmon; Martha Valdivia-Proa; Luis Olmos-Domínguez; Carlos A Aguilar-Salinas; Luis Dávila-Maldonado; Armando Vázquez-Rangel; Vanina Pavia-Aubry; María de Los A Nava-Hernández; Carlos A Hinojosa-Becerril; Juan C Anda-Garay; Manuel O de Los Ríos-Ibarra; Ana C Berni-Betancourt; Julio López-Cuellar; Diego Araiza-Garaygordobil; Romina Rivera-Reyes; Gabriela Borrayo-Sánchez; Mónica Tapia-Hernández; Claudia V Cano-Nigenda; Arturo Guerra-López; Josué Elías-López; Marco A Figueroa-Morales; Bertha B Montaño-Velázquez; Liliana Velasco-Hidalgo; Ana L Rodríguez-Lozano; Claudia Pimentel-Hernández; María M Baquero-Hoyos; Felipe Romero-Moreno; Mario Rodríguez-Vega Journal: Arch Cardiol Mex Date: 2022