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Effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events

A meta-analysis of randomized controlled trials
  • Y. Zhu
  • X. Shen
  • Q. Jiang
  • Z. Wang
  • Z. Wang
  • X. Dong
  • J. Li
  • Q. Han
  • J. Zhao
  • B. Wang
  • L. Liu
Original articles

Abstract

Background

The present meta-analysis was designed to improve statistical power and review the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events.

Methods

PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to May 2017. Studies considered to be eligible were randomized controlled trials about the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. The primary endpoint was positively adjudicated cardiovascular events; the secondary endpoint comprised cardiac mortality, myocardial infarction (MI), coronary revascularization, stroke, and hospitalization for unstable angina.

Results

We included 20 randomized controlled trials involving 67,934 patients. Monoclonal antibodies against PCSK9 were associated with a significant reduction in positively adjudicated cardiovascular events (relative risk [RR] = 0.87; 95% confidence interval [CI] = 0.81–0.93; z = 4.03; p = 0.000), MI (RR = 0.78; 95% CI = 0.71–0.86; z = 4.96; p = 0.000), coronary revascularization (RR = 0.81, 95% CI = 0.75–0.88; z = 4.93; p = 0.000), and stroke (RR = 0.76, 95% CI = 0.65–0.89; z = 3.47; p = 0.001). Monoclonal antibodies against PCSK9 did not reduce hospitalization rates due to unstable angina. The results of subgroup analysis showed that evolocumab was associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke without reducing cardiac mortality. Alirocumab reduced the incidence of cardiac mortality but not of other cardiovascular events, while bococizumab was associated with a reduced risk of stroke.

Conclusion

Monoclonal antibodies against PCSK9 were associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke.

Keywords

Stroke Proprotein convertase, subtilisin-kexin type 9 Low-density lipoprotein cholesterol Cardiovascular disease Meta-analysis 

Wirkungen monoklonaler Antikörper gegen PCSK9 auf klinische kardiovaskuläre Ereignisse

Metaanalyse randomisierter kontrollierter Studien

Zusammenfassung

Hintergrund

Die vorliegende Metaanalyse diente dazu, die statistische Power zu verbessern und die Wirkungen monoklonaler Antikörper gegen PCSK9 auf klinische kardiovaskuläre Ereignisse darzustellen.

Methoden

Die Datenbanken PubMed, Embase, Web of Science und Cochrane Library wurden von Beginn bis Mai 2017 durchsucht. Geeignet erscheinende Studien waren randomisierte kontrollierte Studien zu den Wirkungen monoklonaler Antikörper gegen PCSK9 auf klinische kardiovaskuläre Ereignisse. Primärer Endpunkt waren von einem verblindeten unabhängigen zentralen Entscheidungskomitee positiv beurteilte (adjudizierte) kardiovaskuläre Ereignisse; der sekundäre Endpunkt umfasste kardiale Mortalität, Myokardinfarkt (MI), Koronargefäßrevaskularisierung, Schlaganfall und stationäre Aufnahme wegen instabiler Angina pectoris.

Ergebnisse

Die Autoren schlossen 20 randomisierte kontrollierte Studien mit 67.934 Patienten in ihre Auswertung ein. Monoklonale Antikörper gegen PCSK9 waren mit einer signifikanten Verminderung positiv adjudizierter kardiovaskulärer Ereignisse assoziiert (relatives Risiko, RR = 0,87; 95%-Konfidenzintervall, 95%-KI: 0,81–0,93; Z = 4,03; p = 0,000), MI (RR = 0,78; 95%-KI: 0,71–0,86; Z = 4,96; p = 0,000), Koronargefäßrevaskularisierung (RR = 0,81, 95%-KI: 0,75–0,88; Z = 4,93; p = 0,000) und Schlaganfall (RR = 0,76, 95%-KI: 0,65–0,89; Z = 3,47; p = 0,001). Die Hospitalisierungsraten wegen instabiler Angina pectoris senkten monoklonale Antikörper gegen PCSK9 nicht. Den Ergebnissen der Subgruppenanalyse zufolge war Evolocumab mit einem niedrigeren Risiko für positiv adjudizierte kardiovaskuläre Ereignisse, MI, Koronargefäßrevaskularisierung und Schlaganfall assoziiert, ohne die kardiale Mortalität zu senken. Alirocumab senkte zwar die Inzidenz der kardialen Mortalität, nicht jedoch die anderer kardiovaskulärer Ereignisse, während Bococizumab mit einem verminderten Risiko für einen Schlaganfall assoziiert war.

Schlussfolgerung

Monoklonale Antikörper gegen PCSK9 waren mit einem niedrigeren Risiko für positiv adjudizierte kardiovaskuläre Ereignisse, MI, Koronargefäßrevaskularisierung und Schlaganfall assoziiert.

Schlüsselwörter

Schlaganfall Proproteinkonvertase, Subtilisin-Kexin-Typ 9 Low-Density-Lipoprotein-Cholesterin Herz-Kreislauf-Erkrankung Metaanalyse 

Notes

Compliance with ethical guidelines

Conflict of interest

Y. Zhu, X. Shen, Q. Jiang, Z. Wang, Z. Wang, X Dong, J. Li, Q. Han, J. Zhao, B. Wang, and L. Liu declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors. The ethical guidelines of the studies analyzed in this article are provided within the respective study.

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Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  • Y. Zhu
    • 1
  • X. Shen
    • 2
    • 4
  • Q. Jiang
    • 3
  • Z. Wang
    • 1
  • Z. Wang
    • 1
  • X. Dong
    • 1
  • J. Li
    • 1
  • Q. Han
    • 1
  • J. Zhao
    • 1
  • B. Wang
    • 1
  • L. Liu
    • 1
  1. 1.Dongzhimen HospitalDongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijingChina
  2. 2.Cardiovascular Department of Dongzhimen HospitalDongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijingChina
  3. 3.ICU Department of Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
  4. 4.BeijingChina

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