Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease
Journal
Journal of the American Heart Association
Date Issued
2023-07-14
Author(s)
Bergami, Maria
University of Bologna
Manfrini, Olivia
University of Bologna
Nava, Stefano
Caramori, Gaetano
University of Parma
Yoon, Jinsung
Badimon, Lina
Centro de Investigación y Desarrollo, City University of New York, Consejo Superior de Investigaciones Científicas, Harvard University, Institut de Recerca Sant Pau, Instituto Catalán de Ciencias Cardiovasculares, Massachusetts General Hospital, Mayo Clinic, Mount Sinai Hospital, Universitat de Vic - Universitat Central de Catalunya
Cenko, Edina
University of Bologna
Antonio David
Dorobantu, Maria
Carol Davila University of Medicine and Pharmacy
Fabin, Natalia
Humanitas University, IRCCS Humanitas Research Hospital
Gheorghe-fronea Oana
Jankovic, Radmilo
Ladjevic, Nebojsa
Faculty of Medicine, University of Belgrade, Serbian Pain Society, University Clinical centre of Serbia
Lasica, Ratko
Clnical center of Serbia
Loncar, Goran
Mancuso, Giuseppe
Mendieta, Guiomar
Davor Miličić
Mjehović, Petra
Marijan Pašalić
Milovan Petrović
Scarpone, Marialuisa
Stefanovic, Milena
Van Der Schaar Mihaela
Eindhoven University of Technology, University of Cambridge, University of Oxford
Vasiljevic, Zorana
Medical faculty, University Belgrade
Vega Maria Laura
ALMA MATER STUDIORUM - UNIVERSITA' DI BOLOGNA
Vukomanovic, Vladan
Zdravkovic, Marija
Bugiardini, Raffaele
University of Bologna
DOI
10.1161/JAHA.122.028939 Erratum in
Abstract
Background
Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID‐19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events.
Methods and Results
This study was conducted using data from the ISACS‐COVID‐19 (International Survey of Acute Coronavirus Syndromes‐COVID‐19) registry. Patients with a confirmed diagnosis of SARS‐CoV‐2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30‐day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69–1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42–0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75–2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (
P
interaction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34–3.90]).
Conclusions
These findings suggest that azithromycin use in patients with COVID‐19 and prior history of CVD is significantly associated with an increased risk of AHF and all‐cause 30‐day mortality.
Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID‐19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events.
Methods and Results
This study was conducted using data from the ISACS‐COVID‐19 (International Survey of Acute Coronavirus Syndromes‐COVID‐19) registry. Patients with a confirmed diagnosis of SARS‐CoV‐2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30‐day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69–1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42–0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75–2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (
P
interaction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34–3.90]).
Conclusions
These findings suggest that azithromycin use in patients with COVID‐19 and prior history of CVD is significantly associated with an increased risk of AHF and all‐cause 30‐day mortality.