Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jul 2023)

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID‐19 and Preexisting Cardiovascular Disease

  • Maria Bergami,
  • Olivia Manfrini,
  • Stefano Nava,
  • Gaetano Caramori,
  • Jinsung Yoon,
  • Lina Badimon,
  • Edina Cenko,
  • Antonio David,
  • Ilir Demiri,
  • Maria Dorobantu,
  • Natalia Fabin,
  • Oana Gheorghe‐Fronea,
  • Radmilo Jankovic,
  • Sasko Kedev,
  • Nebojsa Ladjevic,
  • Ratko Lasica,
  • Goran Loncar,
  • Giuseppe Mancuso,
  • Guiomar Mendieta,
  • Davor Miličić,
  • Petra Mjehović,
  • Marijan Pašalić,
  • Milovan Petrović,
  • Lidija Poposka,
  • Marialuisa Scarpone,
  • Milena Stefanovic,
  • Mihaela van der Schaar,
  • Zorana Vasiljevic,
  • Marija Vavlukis,
  • Maria Laura Vega Pittao,
  • Vladan Vukomanovic,
  • Marija Zdravkovic,
  • Raffaele Bugiardini

DOI
https://doi.org/10.1161/JAHA.122.028939
Journal volume & issue
Vol. 12, no. 14

Abstract

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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 (Pinteraction=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. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

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