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Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation

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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.
Oxford University Press (OUP)
Shaun G Goodman Philippe Gabriel Steg Michael Szarek Deepak L Bhatt Vera A Bittner Rafael Diaz Robert A Harrington J Wouter Jukema Harvey D White Andreas M Zeiher Garen Manvelian Robert Pordy Yann Poulouin Wanda Stipek Genevieve Garon Gregory G Schwartz Gregory G Schwartz Ph Gabriel Steg Deepak L Bhatt Vera A Bittner Rafael Diaz 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 Diaz Philip E Aylward Heinz Drexel Peter Sinnaeve Mirza Dilic Renato D Lopes Nina N Gotcheva Shaun G Goodman Juan-Carlos Prieto Huo Yong Patricio López-Jaramillo Ivan Pećin Zeljko 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 Robert Gabor Kiss Denis Xavier Doron Zahger Marco Valgimigli Takeshi Kimura Hyo Soo Kim Sang-Hyun Kim Andrejs Erglis Aleksandras Laucevicius Sasko Kedev Khalid Yusoff Gabriel Arturo Ramos López Marco Alings Harvey D White Sigrun Halvorsen Roger M Correa Flores Rody G Sy Andrzej Budaj Joao Morais Maria Dorobantu Yuri Karpov Arsen D Ristic Terrance Chua Jan Murin 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 G Olsson Jean-Lucien Rouleau Maarten L Simoons Karen Alexander Chiara Meloni Robert Rosenson Eric J G Sijbrands Pierluigi Tricoci John H Alexander Luciana Armaganijan Akshay Bagai Maria Cecilia Bahit J Matthew Brennan Shaun Clifton Adam D DeVore Shalonda Deloatch Sheila Dickey Keith Dombrowski Grégory Ducrocq Zubin Eapen Patricia Endsley Arleen Eppinger Robert W Harrison Connie Ng Hess Mark A Hlatky Joseph Dedrick Jordan 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Lekakis Apostolos Hatzitolios Sergio R Fausto Ovando Pablo Carlos Montenegro Valdovinos Juan L Arango Benecke Edgar R Rodriguez De Leon Bryan P Y Yan David C W Siu Tibor Turi Bela Merkely Robert Gabor Kiss Imre Ungi Geza Lupkovics Lajos Nagy András Katona István Édes Gábor Müller Iván Horvath Tibor Kapin Zsolt Szigeti József Faluközy Mukund Kumbla Manjinder Sandhu Sharath Annam Naveen Reddy Proddutur Reddy Regella Rajendra K Premchand Ajaykumar Mahajan Sudhir Pawar Atul D Abhyanakar Prafulla Kerkar Ravishankar A Govinda Abraham Oomman Dhurjati Sinha Sachin N Patil Dhiman Kahali Jitendra Sawhney Abhijeet B Joshi Sanjeev Chaudhary Pankaj Harkut Santanu Guha Sanjay Porwal Srimannarayana Jujjuru Ramesh B Pothineni Minguel R Monteiro Aziz Khan Shamanna S Iyengar Jasprakash Singh Grewal Manoj Chopda Mahesh C Fulwani Dr Aparna Patange Patil Sachin Vijay K Chopra Naresh K Goyal Rituparna Shinde Gajendra V Manakshe Nitin Patki Sumeet Sethi Vengatesh Munusamy Sunil Karnaand Sunil Thanvi 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Helen M Colhoun Michael A Dempsey Mark A McClanahan
Title: Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation
Description:
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.

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