The association between PCSK9 inhibitor use and sepsis - A systematic review and meta-analysis of 20 double-blind, randomized, placebo-controlled trials

Zhen Zhou; Wei Zhang; David Burgner; Andrew Tonkin; Chao Zhu; Chenyu Sun; Costan G Magnussen; Michael E Ernst; Monique Breslin; Stephen J Nicholls; Mark R Nelson

doi:10.1016/j.amjmed.2023.02.025

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The association between PCSK9 inhibitor use and sepsis - A systematic review and meta-analysis of 20 double-blind, randomized, placebo-controlled trials

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The association between PCSK9 inhibitor use and sepsis - A systematic review and meta-analysis of 20 double-blind, randomized, placebo-controlled trials

Zhen Zhou, Wei Zhang, David Burgner, Andrew Tonkin, Chao Zhu, Chenyu Sun, Costan G Magnussen, Michael E Ernst, Monique Breslin, Stephen J Nicholls, …

The American journal of medicine, Vol.136(6), pp.558-567.e20

06/2023

DOI: 10.1016/j.amjmed.2023.02.025

PMID: 36921646

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Abstract

To determine the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor use on incident sepsis and other severe infections. 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. 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. 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.

infection

PCSK9 inhibitor

drug safety

meta-analysis

sepsis

Details

Title: Subtitle: The association between PCSK9 inhibitor use and sepsis - A systematic review and meta-analysis of 20 double-blind, randomized, placebo-controlled trials
Creators: Zhen Zhou
Wei Zhang - Anhui Medical University
David Burgner
Andrew Tonkin - Monash University
Chao Zhu - Monash University
Chenyu Sun - AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago 60657, Illinois, USA
Costan G Magnussen
Michael E Ernst - University of Iowa
Monique Breslin - University of Tasmania
Stephen J Nicholls - Monash University
Mark R Nelson - University of Tasmania
Resource Type: Journal article
Publication Details: The American journal of medicine, Vol.136(6), pp.558-567.e20
DOI: 10.1016/j.amjmed.2023.02.025
PMID: 36921646
NLM abbreviation: Am J Med
ISSN: 0002-9343
eISSN: 1555-7162
Grant note: DOI: 10.13039/100004312, name: Eli Lilly and Company; DOI: 10.13039/100004337, name: Roche; DOI: 10.13039/501100000925, name: National Health and Medical Research Council, award: APP1175744, APP1176494
Language: English
Electronic publication date: 03/13/2023
Date published: 06/2023
Academic Unit: Family and Community Medicine; Pharmacy Practice and Science
Record Identifier: 9984378332802771

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