open access
Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials


- Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong, China
open access
Abstract
Background: Safety concerns about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors make physicians reluctant to prescribe agents for patients. The present aim was to assess the efficacy and safety of alirocumab, evolocumab and bococizumab in patients with atherosclerotic cardiovascular disease (ASCVD). Methods: Medline, the Cochrane Library and Clinicaltrials.gov were searched for 45 randomized controlled trials, involving 97,297 patients. Results: Compared with the control group, PCSK9 inhibitors could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol. Alirocumab was associated with lower incidence of unstable angina (p < 0.05) and myocardial infarction (p < 0.05), compared with the control group. Alirocumab (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.60–0.97, p < 0.05), evolocumab (OR 0.79, 95% CI 0.66–0.95, p < 0.05) and bococizumab (OR 0.60, 95% CI 0.42–0.84, p < 0.05) were associated with lower incidence of stroke, compared with control group. The incidence of injection-site reactions was significantly higher in alirocumab (OR 1.68, 95% CI 1.45–1.93, p < 0.05), evolocumab (OR 1.64, 95% CI 1.41–1.91, p < 0.05) and bococizumab (OR 8.03, 95% CI 6.85–9.41, p < 0.05) group than in the control group. Conclusions: Alirocumab and evolocumab could ameliorate lipid profile and reduce the risk of cardiac disorders and stroke with satisfactory safety and tolerability. However, injection-site reactions should be paid attention to.
Abstract
Background: Safety concerns about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors make physicians reluctant to prescribe agents for patients. The present aim was to assess the efficacy and safety of alirocumab, evolocumab and bococizumab in patients with atherosclerotic cardiovascular disease (ASCVD). Methods: Medline, the Cochrane Library and Clinicaltrials.gov were searched for 45 randomized controlled trials, involving 97,297 patients. Results: Compared with the control group, PCSK9 inhibitors could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol. Alirocumab was associated with lower incidence of unstable angina (p < 0.05) and myocardial infarction (p < 0.05), compared with the control group. Alirocumab (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.60–0.97, p < 0.05), evolocumab (OR 0.79, 95% CI 0.66–0.95, p < 0.05) and bococizumab (OR 0.60, 95% CI 0.42–0.84, p < 0.05) were associated with lower incidence of stroke, compared with control group. The incidence of injection-site reactions was significantly higher in alirocumab (OR 1.68, 95% CI 1.45–1.93, p < 0.05), evolocumab (OR 1.64, 95% CI 1.41–1.91, p < 0.05) and bococizumab (OR 8.03, 95% CI 6.85–9.41, p < 0.05) group than in the control group. Conclusions: Alirocumab and evolocumab could ameliorate lipid profile and reduce the risk of cardiac disorders and stroke with satisfactory safety and tolerability. However, injection-site reactions should be paid attention to.
Keywords
proprotein convertase subtilisin/kexin type 9, efficacy, safety, meta-analysis




Title
Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials
Journal
Issue
Article type
Original Article
Pages
574-581
Published online
2021-09-23
Page views
5619
Article views/downloads
1221
DOI
Pubmed
Bibliographic record
Cardiol J 2022;29(4):574-581.
Keywords
proprotein convertase subtilisin/kexin type 9
efficacy
safety
meta-analysis
Authors
Qiang Geng
Xuan Li
Qingjiao Sun
Zhengzhong Wang


- Turgeon RD, Tsuyuki RT, Gyenes GT, et al. Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial. Can J Cardiol. 2018; 34(12): 1600–1605.
- Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017; 376(16): 1527–1539.
- Ridker PM, Tardif JC, Amarenco P, et al. Lipid-Reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med. 2017; 376(16): 1517–1526.
- Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine. 2009; 6(7): e1000097.
- Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.
- Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011. http://www.cochrane-handbook.org (accessed 21 March 2011).
- Zhang XL, Zhu QQ, Zhu Li, et al. Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials. BMC Med. 2015; 13: 123.
- Li J, Liang X, Wang Y, et al. Investigation of highly expressed PCSK9 in atherosclerotic plaques and ox-LDL-induced endothelial cell apoptosis. Mol Med Rep. 2017; 16(2): 1817–1825.
- Koskinas KC, Windecker S, Pedrazzini G, et al. Design of the randomized, placebo-controlled evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial. Clin Cardiol. 2018; 41(12): 1513–1520.