Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study
Franck Boccara, Princy N Kumar, Bruno Caramelli, Alexandra Calmy, J Antonio G López, Sarah Bray, Marcoli Cyrille, Robert S Rosenson, BEIJERINCK Investigators, David Baker, Mark Bloch, Robert Finlayson, Jennifer Hoy, Kenneth Koh, Norman Roth, Stephane De Wit, Eric Florence, Linos Vandekerckhove, Bruno Caramelli, Jose Valdez Ramalho Madruga, Sandra Wagner Cardoso, Greg Bondy, Michael Gill, George Tsoukas, Sylvie Trottier, Marek Smieja, Franck Boccara, Christine Katlama, Fabrice Bonnet, Francois Raffi, Laurent Cotte, Jean-Michel Molina, Jacques Reynes, Antonios Papadopoulos, Simeon Metallidis, Vassilios Paparizos, Vasileios Papastamopoulos, Cristina Mussini, Massimo Galli, Andrea Antinori, Antonio Di Biagio, Pierluigi Viale, Andrzej Horban, Nuno Marques, Daniel Coutinho, Joaquim Oliveira, Paula Freitas, Liliana-Lucia Preotescu, Iosif Marincu, Rodica Silaghi, Sorin Rugina, Noluthando Mwelase, Sheena Kotze, Jose Ignacio Bernardino de la Serna, Vicente Estrada Perez, Esteban Martinez, Adrian Curran, Dominique Laurent Braun, Alexandra Calmy, Enos Bernasconi, Matthias Cavassini, John Walsh, Julie Fox, Graeme Moyle, Robert Rosenson, Jamie Morano, Jason Baker, Gerald Pierone, Carl Fichtenbaum, Paul Benson, Deborah Goldstein, Joseph Sacco, Princy Kumar, Robert Grossberg, Kara Chew, Christopher DeFilippi, Vilma Drelichman, Norman Markowitz, David Parenti, Katherine Doktor, Paul Thompson, Franck Boccara, Princy N Kumar, Bruno Caramelli, Alexandra Calmy, J Antonio G López, Sarah Bray, Marcoli Cyrille, Robert S Rosenson, BEIJERINCK Investigators, David Baker, Mark Bloch, Robert Finlayson, Jennifer Hoy, Kenneth Koh, Norman Roth, Stephane De Wit, Eric Florence, Linos Vandekerckhove, Bruno Caramelli, Jose Valdez Ramalho Madruga, Sandra Wagner Cardoso, Greg Bondy, Michael Gill, George Tsoukas, Sylvie Trottier, Marek Smieja, Franck Boccara, Christine Katlama, Fabrice Bonnet, Francois Raffi, Laurent Cotte, Jean-Michel Molina, Jacques Reynes, Antonios Papadopoulos, Simeon Metallidis, Vassilios Paparizos, Vasileios Papastamopoulos, Cristina Mussini, Massimo Galli, Andrea Antinori, Antonio Di Biagio, Pierluigi Viale, Andrzej Horban, Nuno Marques, Daniel Coutinho, Joaquim Oliveira, Paula Freitas, Liliana-Lucia Preotescu, Iosif Marincu, Rodica Silaghi, Sorin Rugina, Noluthando Mwelase, Sheena Kotze, Jose Ignacio Bernardino de la Serna, Vicente Estrada Perez, Esteban Martinez, Adrian Curran, Dominique Laurent Braun, Alexandra Calmy, Enos Bernasconi, Matthias Cavassini, John Walsh, Julie Fox, Graeme Moyle, Robert Rosenson, Jamie Morano, Jason Baker, Gerald Pierone, Carl Fichtenbaum, Paul Benson, Deborah Goldstein, Joseph Sacco, Princy Kumar, Robert Grossberg, Kara Chew, Christopher DeFilippi, Vilma Drelichman, Norman Markowitz, David Parenti, Katherine Doktor, Paul Thompson
Abstract
Background: People living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and are prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens.
Objectives: This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV.
Methods: BEIJERINCK (EvolocumaB Effect on LDL-C Lowering in SubJEcts with Human Immunodeficiency VirRus and INcreased Cardiovascular RisK) is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C <70 mg/dl and percent change in other plasma lipid and lipoprotein levels. Treatment-emergent adverse events were also examined.
Results: A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% confidence interval: 61.6% to 52.3%) from baseline to week 24 versus placebo. An LDL-C level of <70 mg/dl was achieved in 73.3% of patients in the evolocumab group versus 7.9% in the placebo group. Evolocumab also significantly reduced other atherogenic lipid levels, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (all p < 0.0001). Evolocumab was well tolerated, and treatment-emergent adverse events patient incidence was similar among evolocumab and placebo groups.
Conclusions: Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk. (Safety, Tolerability & Efficacy on LDL-C of Evolocumab in Subjects With HIV & Hyperlipidemia/Mixed Dyslipidemia; NCT02833844).
Keywords: cardiovascular disease; hypercholesterolemia; low-density lipoprotein cholesterol (LDL-C); people living with HIV (PLHIV); proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed