Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation
Shaun G. Goodman, Philippe Gabríel Steg, Michael Szarek, Deepak L. Bhatt, Vera Bittner, Rafael Díaz, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Garen Manvelian, Robert Pordy, Yann Poulouin, Wanda Stipek, Geneviève Garon, Gregory G. Schwartz, ODYSSEY OUTCOMES Investigators, Gregory G. Schwartz, Philippe Gabríel Steg, Deepak L. Bhatt, Vera Bittner, Rafael Dı́az, Shaun G Goodman, Robert A. Harrington, J. Wouter Jukema, Michael Szarek, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, Robert Pordy, William J. Sasiela, Jean‐François Tamby, Rafael Dı́az, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilić, Renato D Lopes, Nina Gotcheva, Shaun G Goodman, Juan Carlos Prieto, Huo Yong, Patricio López‐Jaramillo, Ivan Pećin, Željko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Róbert Gábor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo-Soo Kim, Sang‐Hyun Kim, Andrejs Ērglis, Aleksandras Laucevičius, Saško Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Harvey D. White, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, João Morais, Maria Dorobanţu, Yuri Karpov, Arsen Ristić, Terrance Chua, Ján Murín, Zlatko Fras, Anthony J. Dalby, José Tuñón, H Asita de Silva, Emil Hagström, Ulf Landmesser, Chern‐En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Bernard Chaitman, Sheryl F. Kelsey, Anders Olsson
Abstract
The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.