Eric M Mortensen1, Ethan A Halm2, Mary Jo Pugh3, Laurel A Copeland4, Mark Metersky5, Michael J Fine6, Christopher S Johnson1, Carlos A Alvarez7, Christopher R Frei8, Chester Good6, Marcos I Restrepo3, John R Downs3, Antonio Anzueto3. 1. VA North Texas Health Care System, Dallas2University of Texas Southwestern Medical Center, Dallas. 2. University of Texas Southwestern Medical Center, Dallas. 3. VERDICT Research Program, South Texas Veterans Health Care System, San Antonio5University of Texas Health Science Center at San Antonio. 4. Center for Applied Health Research, Central Texas Veterans Health Care System jointly with Scott and White Healthcare, Temple, Texas. 5. University of Connecticut Medical Center, Farmington. 6. VA Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, Pennsylvania. 7. VA North Texas Health Care System, Dallas2University of Texas Southwestern Medical Center, Dallas3Texas Tech University Health Sciences Center, Dallas. 8. University of Texas Health Science Center at San Antonio9University of Texas at Austin.
Abstract
IMPORTANCE: Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE: To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN: Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING: This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS: Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES: Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS: Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE: Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.
IMPORTANCE: Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE: To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN: Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING: This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS: Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES: Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS: Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE: Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.
Authors: José A Martínez; Juan P Horcajada; Manuel Almela; Francesc Marco; Alex Soriano; Elisa García; Maria Angeles Marco; Antoni Torres; Josep Mensa Journal: Clin Infect Dis Date: 2003-01-31 Impact factor: 9.079
Authors: Thomas P Lodise; Andrea Kwa; Leon Cosler; Reetu Gupta; Raymond P Smith Journal: Antimicrob Agents Chemother Date: 2007-08-20 Impact factor: 5.191
Authors: J L Anderson; J B Muhlestein; J Carlquist; A Allen; S Trehan; C Nielson; S Hall; J Brady; M Egger; B Horne; T Lim Journal: Circulation Date: 1999-03-30 Impact factor: 29.690
Authors: T P Meehan; M J Fine; H M Krumholz; J D Scinto; D H Galusha; J T Mockalis; G F Weber; M K Petrillo; P M Houck; J M Fine Journal: JAMA Date: 1997-12-17 Impact factor: 56.272
Authors: Chih-Hsin Hsu; Luis F Reyes; Carlos J Orihuela; Ricardo Buitrago; Antonio Anzueto; Nilam J Soni; Stephanie Levine; Jay Peters; Cecilia A Hinojosa; Stefano Aliberti; Oriol Sibila; Alejandro Rodriguez; James D Chalmers; Ignacio Martin-Loeches; Jose Bordon; Jose Blanquer; Francisco Sanz; Pedro J Marcos; Jordi Rello; Jordi Solé-Violán; Marcos I Restrepo Journal: Biomarkers Date: 2015-07-08 Impact factor: 2.658
Authors: Mai H Trac; Eric McArthur; Racquel Jandoc; Stephanie N Dixon; Danielle M Nash; Daniel G Hackam; Amit X Garg Journal: CMAJ Date: 2016-02-22 Impact factor: 8.262
Authors: Yoriko Heianza; Wenjie Ma; Xiang Li; Yin Cao; Andrew T Chan; Eric B Rimm; Frank B Hu; Kathryn M Rexrode; JoAnn E Manson; Lu Qi Journal: Circ Res Date: 2019-12-17 Impact factor: 17.367
Authors: Zhiqiang Kevin Lu; Jing Yuan; Minghui Li; S Scott Sutton; Gowtham A Rao; Sony Jacob; Charles L Bennett Journal: Expert Opin Drug Saf Date: 2014-12-10 Impact factor: 4.250