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

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

The Evolving Challenge of Appropriate Antibiotics Use in Hospitalized COVID-19 Patients: A Systematic Literature Review

“…Two hundred-three studies were excluded because they did not report data on antibiotic use in COVID-19 patients. Of the remaining 77 studies, 29 studies were included in this systematic review [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] ( Table 1 ).…”

“…Of the 29 studies included in the systematic review, 18 studies were on the prevalence of bacterial infection and antibiotics use in hospitalized COVID-19 patients [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]; of these studies, 5 reported on patients admitted to the intensive care unit [ 20 , 21 , 22 , 23 , 24 ]. Four studies reported on the efficacy of early antibiotic use in hospitalized COVID-19 patients [ 25 , 26 , 27 , 28 ]; four studies were on the use of sepsis biomarkers to improve antibiotic use among COVID-19 patients [ 29 , 30 , 31 , 32 ]; three studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19 hospitalized patients [ 33 , 34 , 35 ].…”

“…Among the 29 included studies, 23 studies were retrospective, observational studies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 29 , 30 , 35 ]; 4 studies were observational, before–after studies [ 28 , 32 , 33 , 34 ]; and 2 studies were randomized, open-label, controlled trials [ 25 , 31 ].…”

“…A retrospective cohort study analysed 4462 COVID-19 patients to assess the advantages and disadvantages of administering azithromycin within 24 h of hospital admission, compared to standard care. The study found that azithromycin treatment was consistently linked to a higher risk of acute heart failure in patients with pre-existing cardiovascular disease (risk ratio: 1.48, 95% CI: 1.06–2.06) [ 27 ].…”