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Canadian Journal of Cardiology
Brief Rapid Report| Volume 34, ISSUE 12, P1600-1605, December 2018

Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial

      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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      References

        • Anderson T.J.
        • Grégoire J.
        • Pearson G.J.
        • et al.
        2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
        Can J Cardiol. 2016; 32: 1263-1282
        • Waters D.D.
        • Boekholdt S.M.
        An evidence-based guide to cholesterol-lowering guidelines.
        Can J Cardiol. 2017; 33: 343-349
        • Anderson T.J.
        Optimal low-density lipoprotein cholesterol for cardiovascular prevention: how low should we go?.
        Can J Cardiol. 2017; 33: 405-408
        • Bergeron N.
        • Phan B.A.
        • Ding Y.
        • Fong A.
        • Krauss R.M.
        Proprotein convertase subtilisin/kexin type 9 inhibition a new therapeutic mechanism for reducing cardiovascular disease risk.
        Circulation. 2015; 132: 1648-1666
        • Sabatine M.S.
        • Giugliano R.P.
        • Keech A.C.
        • et al.
        Evolocumab and clinical outcomes in patients with cardiovascular disease.
        N Engl J Med. 2017; 376: 1713-1722
      1. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome [Epub ahead of print]. N Engl J Med, https://doi.org/10.1056/NEJMoa1801174, accessed November 9, 2018.

        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        PLoS Med. 2009; 6: e1000100
        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Balshem H.
        • Helfand M.
        • Schünemann H.J.
        • et al.
        GRADE guidelines: 3. Rating the quality of evidence.
        J Clin Epidemiol. 2011; 64: 401-406
        • Schmidt A.F.
        • Pearce L.S.
        • Wilkins J.T.
        • et al.
        PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
        Cochrane Database Syst Rev. 2017; : CD011748
        • Karatasakis A.
        • Danek B.A.
        • Karacsonyi J.
        • et al.
        Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: a meta-analysis of 35 randomized controlled trials.
        J Am Heart Assoc. 2017; 6: e006910
        • Hlatky M.A.
        • Kazi D.S.
        PCSK9 inhibitors: economics and policy.
        J Am Coll Cardiol. 2017; 70: 2677-2687
        • Ference B.A.
        • Robinson J.G.
        • Brook R.D.
        • et al.
        Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes.
        N Engl J Med. 2016; 375: 2144-2153
        • Schmidt A.F.
        • Swerdlow D.I.
        • Holmes M.V.
        • et al.
        PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study.
        Lancet Diabetes Endocrinol. 2017; 5: 97-105