Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering
agents, but more precise estimates of their effects on major adverse cardiovascular
events (MACE), mortality, and safety are needed. We systematically reviewed and meta-analyzed
randomized controlled trials with durations ≥ 6 months comparing MACE, mortality,
and safety with PCSK9 inhibitors vs control. We searched CENTRAL, Embase, MedLine
and the grey literature to November 7, 2018. From 2048 articles, we included 23 trials
(n = 60,723). PCSK9 inhibitors reduced MACE (relative risk, 0.83; 95% confidence interval,
0.78-0.88), but did not clearly reduce mortality (relative risk, 0.93; 95% confidence
interval, 0.85-1.02) or increase adverse events. In conclusion, PCSK9 inhibitors reduce
nonfatal MACE, are well tolerated, but effects on mortality remain unclear.
Résumé
Les inhibiteurs de la proprotéine convertase subtilisine/kexine de type 9 (PCSK9)
sont des agents hypolipidémiants efficaces, mais il est nécessaire d’estimer de façon
plus précise leur innocuité ainsi que leurs effets sur les événements indésirables
cardiovasculaires majeurs (EICM) et la mortalité. Nous avons effectué une recension
systématique et une méta-analyse des essais randomisés contrôlés d’une durée supérieure
à 6 mois pour comparer les EICM, la mortalité et l’innocuité des inhibiteurs de la
PCSK9 comparativement à des témoins. Nos recherches ont porté sur les publications
dans les bases de données CENTRAL, Embase et MedLine et la littérature grise jusqu’au
7 novembre 2018. À partir de 2048 articles recensés, nous avons analysé 23 essais
(n = 60 723). Les inhibiteurs de la PCSK9 ont réduit les EICM (risque relatif, 0,83;
intervalle de confiance à 95 % : de 0,78 à 0,88), mais n’ont pas réduit la mortalité
de façon nette (risque relatif, 0,93; intervalle de confiance à 95 % : de 0,85 à 1,02)
ou entraîné une augmentation des événements indésirables. En conclusion, les inhibiteurs
de la PCSK9 réduisent la fréquence des EICM non mortels et sont bien tolérés, mais
leurs effets sur la mortalité restent à déterminer.
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Article info
Publication history
Accepted:
April 2,
2018
Received:
March 16,
2018
Footnotes
See page 1604 for disclosure information.
Identification
Copyright
© 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.