Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.
LDL cholesterol
Major cardiovascular events
Meta-analysis
Mortality
PCSK-9 inhibitors
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
28
10
2018
accepted:
07
02
2019
pubmed:
15
2
2019
medline:
25
1
2020
entrez:
15
2
2019
Statut:
ppublish
Résumé
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. PROSPERO-CRD42018087640.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality.
METHODS AND RESULTS
RESULTS
A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]).
CONCLUSIONS
CONCLUSIONS
PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE.
REGISTRATION NUMBER
BACKGROUND
PROSPERO-CRD42018087640.
Identifiants
pubmed: 30762200
doi: 10.1007/s40618-019-01019-4
pii: 10.1007/s40618-019-01019-4
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Anticholesteremic Agents
0
Cholesterol, LDL
0
PCSK9 Inhibitors
0
PCSK9 protein, human
EC 3.4.21.-
evolocumab
LKC0U3A8NJ
alirocumab
PP0SHH6V16
Types de publication
Journal Article
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1029-1039Références
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