{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:17:08Z","timestamp":1776370628558,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Studies suggest that clarithromycin is associated with an increased risk of major adverse cardiovascular events (MACE) among adults with coronary artery disease. However, data comparing clarithromycin to other macrolides, such as azithromycin, in a broader population are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multicenter study was conducted in 33 hospitals in Ontario, Canada, and Copenhagen, Denmark, using the Target Trial framework. Adults hospitalized with community\u2010acquired pneumonia (CAP) who received either clarithromycin or azithromycin were included. The primary outcome was MACE, defined as the one\u2010year risk of nonfatal myocardial infarction, nonfatal stroke, or all\u2010cause mortality. Propensity score matching and Cox proportional hazards models were used for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In Ontario, we identified 23\u2009081 patients with CAP, and 11\u2009164 received oral macrolides. After propensity score matching, the primary outcome occurred in 7.8% of clarithromycin patients and 9.1% of azithromycin patients (HR 0.85, 95% CI 0.60\u20131.21). In Copenhagen, there were 11\u2009280 patients with CAP and 3924 received oral macrolides. After propensity score matching, 19% of clarithromycin patients and 12% of azithromycin patients experienced the primary outcome for oral macrolides (HR 1.7, 95% CI 1.2\u20132.4, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Meta\u2010analysis of the point estimate from each country provided an overall HR of 1.21 (95% CI 0.61\u20132.39). For intravenous macrolides in Copenhagen, the HR was 1.15 (95% CI 1.0\u20131.3, <jats:italic>p<\/jats:italic>\u2009=\u20090.007) for clarithromycin compared to azithromycin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study did not consistently observe an increased risk of cardiovascular events with clarithromycin among adults hospitalized with CAP. However, the observational nature of the study may introduce selection bias and unmeasured confounding.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.70163","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T06:20:24Z","timestamp":1749277224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clarithromycin Versus Azithromycin for Community\u2010Acquired Pneumonia and the Risk of Major Adverse Cardiovascular Events: A Multicentre Cohort Study Using Data From Canada and Denmark"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1204-3636","authenticated-orcid":false,"given":"Theis Skovsgaard","family":"Itenov","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony D.","family":"Bai","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tor","family":"Biering\u2010S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Cardiovascular Non\u2010Invasive Imaging Research Laboratory, Department of Cardiology, Herlev and Gentofte Hospital University of Copenhagen  Hellerup Denmark"},{"name":"Center for Translational Cardiology and Pragmatic Randomized Trials, Faculty of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Cardiology Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"},{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amol","family":"Verma","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto  Toronto Canada"},{"name":"Institute of Health Policy, Management and Evaluation University of Toronto  Toronto Canada"},{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Canada"},{"name":"Department of Medicine University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahad","family":"Razak","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto  Toronto Canada"},{"name":"Institute of Health Policy, Management and Evaluation University of Toronto  Toronto Canada"},{"name":"Department of Medicine University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hospital Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Department of Pediatrics, Division of Hospital\u2010Based Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Bundgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Cardiology Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeesh","family":"Sivapalan","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Section of Respiratory Medicine, Department of Medicine Copenhagen University Hospital \u2013 Herlev and Gentofte Hospital  Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasper","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Medicine Copenhagen University Hospital \u2013 Herlev and Gentofte Hospital  Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Copenhagen University Hospital \u2013 Amager and Hvidovre Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotte","family":"Klitfod","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Copenhagen University Hospital \u2013 Herlev and Gentofte Hospital  Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrine","family":"Dircks","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Copenhagen University Hospital \u2013 Amager and Hvidovre Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens\u2010Ulrik S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Section of Respiratory Medicine, Department of Medicine Copenhagen University Hospital \u2013 Herlev and Gentofte Hospital  Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2082-2445","authenticated-orcid":false,"given":"Mike","family":"Fralick","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Canada"},{"name":"Sinai Health System  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Dansk Lungemedicinsk Selskab \u201cRetningslinjer for H\u00e5ndtering af Voksne Patienter Indlagt Med Pneumoni \u201d2021 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