An evaluation of co-use of chloroquine or hydroxychloroquine plus azithromycin on cardiac outcomes: A pharmacoepidemiological study to inform use during the COVID19 pandemic.

CI, confidence interval COPD, Chronic obstructive pulmonary disease COVID19 Cardiac events Chloroquine FDA, U.S. Food & Drug Administration HR, hazard ratio Hydroxychloroquine QTc prolongation SCA/VA, sudden cardiac arrest and ventricular arrhythmias SIPTW, Standardized inverse probability treatment weighting

Journal

Research in social & administrative pharmacy : RSAP
ISSN: 1934-8150
Titre abrégé: Res Social Adm Pharm
Pays: United States
ID NLM: 101231974

Informations de publication

Date de publication:
01 2021
Historique:
received: 27 04 2020
accepted: 28 04 2020
pubmed: 16 5 2020
medline: 29 12 2020
entrez: 16 5 2020
Statut: ppublish

Résumé

Chloroquine or hydroxychloroquine (chloroquine) plus azithromycin is considered as therapy for COVID-19. With benefit evaluations underway, safety concerns due to potential additive effects on QTc prolongation should be addressed. We compared risk of cardiac adverse events between combinations of chloroquine and azithromycin and chloroquine and amoxicillin. We conducted a retrospective cohort study using the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, 2005-2018. We included autoimmune disease patients aged ≥18 years initiating azithromycin or amoxicillin for ≥5 days during chloroquine treatment. Patients had continuous insurance coverage ≥6 months before combination use until 5 days thereafter or inpatient death. Two outcomes were sudden cardiac arrest/ventricular arrhythmias (SCA/VA) and cardiac symptoms. We followed patients for up to 5 days to estimate hazard ratios (HR). Covariates were adjusted using stabilized inverse probability treatment weighting. We identified two SVC/VA events among >145,000 combination users. The adjusted incidence of cardiac symptoms among azithromycin and amoxicillin users was 276 vs 254 per 10,000 person-years with an adjusted HR of 1.10 (95%CI, 0.62-1.95). Combination use of chloroquine and azithromycin at routine doses did not show pronounced increases in arrhythmias in this real-world population, though small sample size and outcome rates limit conclusions.

Sections du résumé

Background
Chloroquine or hydroxychloroquine (chloroquine) plus azithromycin is considered as therapy for COVID-19. With benefit evaluations underway, safety concerns due to potential additive effects on QTc prolongation should be addressed.
Objective
We compared risk of cardiac adverse events between combinations of chloroquine and azithromycin and chloroquine and amoxicillin.
Methods
We conducted a retrospective cohort study using the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, 2005-2018. We included autoimmune disease patients aged ≥18 years initiating azithromycin or amoxicillin for ≥5 days during chloroquine treatment. Patients had continuous insurance coverage ≥6 months before combination use until 5 days thereafter or inpatient death. Two outcomes were sudden cardiac arrest/ventricular arrhythmias (SCA/VA) and cardiac symptoms. We followed patients for up to 5 days to estimate hazard ratios (HR). Covariates were adjusted using stabilized inverse probability treatment weighting.
Results
We identified two SVC/VA events among >145,000 combination users. The adjusted incidence of cardiac symptoms among azithromycin and amoxicillin users was 276 vs 254 per 10,000 person-years with an adjusted HR of 1.10 (95%CI, 0.62-1.95).
Conclusion
Combination use of chloroquine and azithromycin at routine doses did not show pronounced increases in arrhythmias in this real-world population, though small sample size and outcome rates limit conclusions.

Identifiants

pubmed: 32409150
pii: S1551-7411(20)30468-X
doi: 10.1016/j.sapharm.2020.04.031
pmc: PMC7190482
pii:
doi:

Substances chimiques

Hydroxychloroquine 4QWG6N8QKH
Azithromycin 83905-01-5
Chloroquine 886U3H6UFF

Types de publication

Evaluation Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2012-2017

Subventions

Organisme : NIA NIH HHS
ID : P30 AG028740
Pays : United States

Informations de copyright

© 2020 Elsevier Inc. All rights reserved.

Références

JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Res Social Adm Pharm. 2021 Feb;17(2):483-486
pubmed: 32327397
Pharmacotherapy. 2019 Dec;39(12):1167-1178
pubmed: 31674031
Int J Antimicrob Agents. 2020 Jul;56(1):105949
pubmed: 32205204
N Engl J Med. 2012 May 17;366(20):1881-90
pubmed: 22591294
Drug Saf. 2018 Oct;41(10):919-931
pubmed: 29858838
Biomed Res Int. 2018 Oct 14;2018:1574806
pubmed: 30406128
Med (N Y). 2020 Dec 18;1(1):114-127.e3
pubmed: 32838355
Med Mal Infect. 2020 Jun;50(4):384
pubmed: 32240719
Pharmacoepidemiol Drug Saf. 2010 Jun;19(6):555-62
pubmed: 19844945
Int J Rheum Dis. 2020 May;23(5):613-619
pubmed: 32281213

Auteurs

Scott M Vouri (SM)

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA; Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL, USA; University of Florida Health Physicians, Gainesville, FL, USA.

Thuy N Thai (TN)

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.

Almut G Winterstein (AG)

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA; Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL, USA. Electronic address: almut@cop.ufl.edu.

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Classifications MeSH