Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care

Alispahic, Imane Achir; Eklöf, Josefin; Sivapalan, Pradeesh; Jordan, Alexander Ryder; Harboe, Zitta Barrella; Biering-Sørensen, Tor; Leth-Møller, Katja Biering; Linneberg, Allan; Jensen, Jens-Ulrik Stæhr

doi:10.3390/biomedicines14061197

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Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care

by

Imane Achir Alispahic

^1,*,

Josefin Eklöf

¹

,

Pradeesh Sivapalan

^1,2,*

,

Alexander Ryder Jordan

¹,

Zitta Barrella Harboe

³

,

Tor Biering-Sørensen

⁴,

Katja Biering Leth-Møller

⁵,

Allan Linneberg

^2,5

and

Jens-Ulrik Stæhr Jensen

^1,2

¹

Department of Internal Medicine, Respiratory Medicine Section, Herlev and Gentofte Hospital, University Hospital of Copenhagen, 2900 Copenhagen, Denmark

²

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2000 Copenhagen, Denmark

³

Department of Respiratory and Infectious Diseases, Copenhagen University Hospital, 3400 North Zealand, Denmark

⁴

Department of Cardiology, Gentofte University Hospital, 2900 Hellerup, Denmark

⁵

Center for Clinical Research and Prevention, Copenhagen University Hospital–Bispebjerg and Frederiksberg, 2000 Copenhagen, Denmark

^*

Authors to whom correspondence should be addressed.

Biomedicines 2026, 14(6), 1197; https://doi.org/10.3390/biomedicines14061197 (registering DOI)

Submission received: 20 April 2026 / Revised: 12 May 2026 / Accepted: 21 May 2026 / Published: 25 May 2026

(This article belongs to the Section Molecular and Translational Medicine)

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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition where many patients are given antibiotics like amoxicillin and macrolides (clarithromycin, azithromycin, roxithromycin) for bacterial infections. Recent concerns about clarithromycin’s potential link to cardiovascular events have arisen, despite its effectiveness against respiratory pathogens. This study aims to compare the cardiovascular risk of macrolide antibiotics versus amoxicillin in suspected COPD patients. Method: We used the Danish National Health Service Prescription Database (DNHSP) to identify COPD patients and their use of antibiotics. The included COPD patients were divided into four groups: amoxicillin users, roxithromycin users, clarithromycin users and azithromycin users. Data from multiple registries were merged to track hospitalizations, causes of death, and major adverse cardiovascular events (MACEs) as the primary endpoint. Patients were followed for a 3-year period. We applied adjusted Cox regression and sensitivity analyses with IPTW and IPCW to address confounders and censoring. Results: Our study involved 45,869 patients who were prescribed a long-acting muscarinic antagonist, over the age of 40 years old and who received one of the following antibiotics: amoxicillin, azithromycin, clarithromycin, or roxithromycin. No increased risk of MACEs was observed in macrolide-treated patients compared to those treated with amoxicillin (azithromycin: HR 0.97: 95% CI 0.83–1.13 p = 0.69, clarithromycin: HR 1.06 95% CI 0.87–1.28 p = 0.57, roxithromycin: HR 1.04 95% CI 0.91–1.18 p = 0.60), as confirmed by the sensitivity analysis (azithromycin: HR 0.95 95% CI 0.82–1.11 p = 0.52, clarithromycin: HR 1.05 95% CI 0.87–1.27 p = 0.60, roxithromycin: HR 1.05 95% CI 0.92–1.19 p = 0.48). Similarly, hazard ratios for all-cause mortality and cardiovascular death among the antibiotic groups showed no significant statistical differences. Conclusions: These findings suggest that there is no difference in the risk of MACEs, all-cause mortality, or cardiovascular death between the amoxicillin group and the macrolide group in a large and unselected population of COPD patients.

Keywords: COPD; stroke; AMI; major adverse cardiovascular event; macrolide; clarithromycin; amoxicillin; azithromycin; roxithromycin

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MDPI and ACS Style

Alispahic, I.A.; Eklöf, J.; Sivapalan, P.; Jordan, A.R.; Harboe, Z.B.; Biering-Sørensen, T.; Leth-Møller, K.B.; Linneberg, A.; Jensen, J.-U.S. Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care. Biomedicines 2026, 14, 1197. https://doi.org/10.3390/biomedicines14061197

AMA Style

Alispahic IA, Eklöf J, Sivapalan P, Jordan AR, Harboe ZB, Biering-Sørensen T, Leth-Møller KB, Linneberg A, Jensen J-US. Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care. Biomedicines. 2026; 14(6):1197. https://doi.org/10.3390/biomedicines14061197

Chicago/Turabian Style

Alispahic, Imane Achir, Josefin Eklöf, Pradeesh Sivapalan, Alexander Ryder Jordan, Zitta Barrella Harboe, Tor Biering-Sørensen, Katja Biering Leth-Møller, Allan Linneberg, and Jens-Ulrik Stæhr Jensen. 2026. "Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care" Biomedicines 14, no. 6: 1197. https://doi.org/10.3390/biomedicines14061197

APA Style

Alispahic, I. A., Eklöf, J., Sivapalan, P., Jordan, A. R., Harboe, Z. B., Biering-Sørensen, T., Leth-Møller, K. B., Linneberg, A., & Jensen, J.-U. S. (2026). Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care. Biomedicines, 14(6), 1197. https://doi.org/10.3390/biomedicines14061197

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Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care

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