Internal and Emergency Medicine

, Volume 12, Issue 7, pp 1043–1053 | Cite as

PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis

  • Alessandro Squizzato
  • Matteo Basilio Suter
  • Marta Nerone
  • Robert Patrick Giugliano
  • Francesco Dentali
  • Andrea Maria Maresca
  • Leonardo Campiotti
  • Anna Maria Grandi
  • Luigina Guasti


Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality, but many patients do not adequately reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in the advanced phase of development. We aimed to investigate the efficacy and safety of PCSK9 inhibitors in patients at different cardiovascular risk in a systematic review. Studies were searched on MEDLINE and EMBASE until January 2016. Differences in the outcomes among groups were expressed as mean differences, or pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. 22 RCTs and 8833 patients were included. Six studies were performed in patients affected by homozygous or heterozygous familial hypercholesterolemia, or with increased cardiovascular risk, two in patients with statin intolerance, three in statin-naïve patients, and 10 in patients unable to achieve LDL-C target with statin therapy. PCSK9 inhibitors were associated with a statistically significant reduction of LDL-C (mean = −48.8%; 95% CI −54.1, −43.4; I 2 = 94%) compared to control groups, and with a statistically significant reduction in death for any cause (OR = 0.34; 95% CI 0.17, 0.69; I 2 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I 2 = 0%). PCSK9 inhibitors reduce LDL-C concentration in every group explored. A significant reduction in death by all cause was observed in the PCSK9 inhibitors groups, compared with control groups, even in the short time frame studied.


Lipid lowering drugs PCSK-9 inhibitors Monoclonal antibodies Dyslipidemia 


Compliance with ethical standards

Conflict of interest

Dr. Giugliano reports grants and personal fees from Amgen, personal fees from Sanofi, personal fees from Regeneron, grants and personal fees from Merck, personal fees from Pfizer, personal fees from Bristol Myers Squibb, outside the submitted work. Nothing to declare from the other authors.

Statement of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent



No organization funded our paper.

Supplementary material

11739_2017_1708_MOESM1_ESM.docx (178 kb)
Supplementary material 1 (DOCX 177 kb)


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Copyright information

© SIMI 2017

Authors and Affiliations

  • Alessandro Squizzato
    • 1
    • 2
  • Matteo Basilio Suter
    • 3
  • Marta Nerone
    • 3
  • Robert Patrick Giugliano
    • 4
  • Francesco Dentali
    • 1
    • 2
  • Andrea Maria Maresca
    • 1
  • Leonardo Campiotti
    • 1
  • Anna Maria Grandi
    • 1
  • Luigina Guasti
    • 1
  1. 1.Department of Medicine and Surgery, Research Center on DyslipidaemiaUniversity of InsubriaVareseItaly
  2. 2.Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic TherapiesUniversity of InsubriaVareseItaly
  3. 3.Department of Medical OncologyOspedale di Circolo e Fondazione Macchi, ASST Sette LaghiVareseItaly
  4. 4.Cardiovascular MedicineBrigham and Women’s HospitalBostonUSA

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