Clinical Significance
- •PCSK9 inhibitors are a class of novel, potent lipid-lowering therapies.
- •Respiratory infections are common adverse events reported by PCSK9 inhibitor users.
- •This meta-analysis found no association of PCSK9 inhibitor use with sepsis and severe infections.
ABSTRACT
Aims
To determine the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor
use on incident sepsis and other severe infections.
Methods
We searched PubMed, EMBASE, CENTRAL and ClinicalTrial.gov up to September 14, 2021
for double-blind, placebo-controlled randomized trials of alirocumab, evolocumab,
or inclisiran with >100 participants in each arm and report of serious adverse events
related to infection. Data were synthesized with the fixed-effect Mantel-Haenszel
model to generate risk ratios (RRs) with 95% confidence intervals (CIs) of each outcome
for PCSK9 inhibitor versus placebo. Main outcome was sepsis. Other outcomes were total
severe infections, severe bacterial and viral infections, and severe organ system-specific
infections including respiratory tract, gastrointestinal, and genitourinary tract
infections.
Results
Twenty studies of 64,984 participants were included (alirocumab: n=7; evolocumab:
n=9; inclisiran: n=4). Sepsis was reported in 292 (0.51%) participants from 11 trials
(PCSK9 inhibitor 0.47%; placebo 0.56%). PCSK9 inhibitor use was not associated with
risk of sepsis compared with placebo (Summary RR: 0.85, 95%CI: 0.67-1.07, P=.16); nor was it associated with any severe infection (0.96, 95% CI 0.89-1.03), severe
bacterial (0.96, 95%CI 0.81-1.14) and viral infections (1.03, 95%CI 0.78-1.37); nor
with any severe organ system-specific infection (all P values >0.05). The between-study heterogeneity in all analyses was small.
Conclusion
There was neither a beneficial nor a harmful association between PCSK9 inhibitors
and risk of sepsis or severe infections. These findings provide reassurance regarding
the safety of PCSK9 inhibitors in patients who are concerned about potential drug
side effects related to infections.
Keywords
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Article info
Publication history
Accepted:
February 14,
2023
Received:
October 24,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
