PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis - PubMed (original) (raw)
PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis
Xing Wang et al. Cardiovasc Diabetol. 2022.
Abstract
Background: The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors.
Methods: Several databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events.
Results: Overall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72-0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04-1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90-0.99).
Conclusions: In consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.
Keywords: Atherosclerosis; Cardiovascular disease; PCSK9 inhibitors; Secondary prevention.
© 2022. The Author(s).
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
Fig. 1
Summary of the primary efficacy outcome. A Network plot of all-cause mortality. The width of the lines is proportional to the number of studies comparing every pair of treatments, and the size of each circle is proportional to the number of participants. B The forest plot shows the risk ratio (RR) and credible interval (CrI). C SUCRA-based ranking probabilities graph of each medication. The SUCRA values for each treatment were as follows: 91% for alirocumab; 24% for evolocumab; 44% for inclisiran. SUCRA surface under the cumulative ranking curve
Fig. 2
A Meta-regression analysis for the interaction of BMI on the risk of all-cause mortality. The BMI value was extracted from the control group in each trial. BMI body mass index. B Meta-regression analysis for the interaction of proportion of diabetic patients on the risk of all-cause mortality. The diabetes data was extracted from the control group in each trial
Fig. 3
Network analysis for secondary efficacy outcomes. A The forest plot for cardiovascular death. B The SUCRA value of each treatment for cardiovascular death. C The forest plot for myocardial infarction. D The SUCRA value of each treatment for myocardial infarction. E The forest plot for stroke. F The SUCRA value of each treatment for stroke. CrI credible interval, SUCRA surface under the cumulative ranking curve
Fig. 4
Summary of the primary safety outcome. A Network plot of serious adverse events. The width of the lines is proportional to the number of studies comparing every pair of treatments, and the size of each circle is proportional to the number of participants. B The forest plot shows the risk ratio (RR) and credible interval (CrI). C SUCRA-based ranking probabilities graph of each medication. The SUCRA values for each treatment were as follows: 77% for alirocumab; 20% for evolocumab; 83% for inclisiran. SUCRA surface under the cumulative ranking curve
Fig. 5
Network analysis for secondary safety outcomes. A The forest plot for injection site reaction. B The SUCRA value of each treatment for injection site reaction. C The forest plot for new-onset diabetes. D The SUCRA value of each treatment for new-onset diabetes. E The forest plot for neurocognitive disorders. F The SUCRA value of each treatment for neurocognitive disorders. CrI credible interval, SUCRA surface under the cumulative ranking curve
Fig. 6
Meta-regression analysis for the interaction of difference between PCSK9 inhibitors group and control group in LDL-C level change on the risk of new-onset diabetes. LDL-C low-density lipoprotein cholesterol, PCSK9 proprotein convertase subtilisin/kexin 9
References
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