Evidence map›Paper›PMID 40481686›Full record

Observational studyPharmacoepidemiology and drug safety2025

Clarithromycin Versus Azithromycin for Community-Acquired Pneumonia and the Risk of Major Adverse Cardiovascular Events: A Multicentre Cohort Study Using Data From Canada and Denmark.

Theis Skovsgaard Itenov, Anthony D Bai, Tor Biering-Sørensen, Amol Verma, Fahad Razak, Ajay Bhasin, Henning Bundgaard, Pradeesh Sivapalan, Kasper Iversen, Christian Rasmussen and 5 more

Abstract readComparative StudyMulticenter StudyObservational Study
In one paragraph

Observational study in Pharmacoepidemiology and drug safety, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Theis Skovsgaard ItenovDepartment of Anesthesiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.ORCID https://orcid.org/0000-0002-1204-3636
Anthony D BaiDivision of Infectious Diseases, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Tor Biering-SørensenCardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Amol VermaLi Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada.
Fahad RazakLi Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada.
Ajay BhasinDepartment of Medicine, Division of Hospital Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Henning BundgaardDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Pradeesh SivapalanDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Kasper IversenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Christian RasmussenDepartment of Emergency Medicine, Copenhagen University Hospital - Amager and Hvidovre Hospital, Copenhagen, Denmark.
Jens RasmussenDepartment of Emergency Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Lotte KlitfodDepartment of Emergency Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Hellerup, Denmark.
Kathrine DircksDepartment of Emergency Medicine, Copenhagen University Hospital - Amager and Hvidovre Hospital, Copenhagen, Denmark.
Jens-Ulrik S JensenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Mike FralickDepartment of Medicine, University of Toronto, Toronto, Canada.ORCID https://orcid.org/0000-0002-2082-2445

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStudies 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.

methodsA multicenter study was conducted in 33 hospitals in Ontario, Canada, and Copenhagen, Denmark, using the Target Trial framework. Adults hospitalized with community-acquired pneumonia (CAP) who received either clarithromycin or azithromycin were included. The primary outcome was MACE, defined as the one-year risk of nonfatal myocardial infarction, nonfatal stroke, or all-cause mortality. Propensity score matching and Cox proportional hazards models were used for analysis.

resultsIn Ontario, we identified 23 081 patients with CAP, and 11 164 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 0.60-1.21). In Copenhagen, there were 11 280 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 1.2-2.4, p = 0.002). Meta-analysis of the point estimate from each country provided an overall HR of 1.21 (95% CI 0.61-2.39). For intravenous macrolides in Copenhagen, the HR was 1.15 (95% CI 1.0-1.3, p = 0.007) for clarithromycin compared to azithromycin.

conclusionThis 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.

Indexed as

Anti-Bacterial AgentsAzithromycinCardiovascular DiseasesClarithromycinCommunity-Acquired InfectionsPneumoniaAdultAgedAged, 80 and overCanadaCohort StudiesCommunity-Acquired PneumoniaDenmarkFemaleHumansMaleAnti-Bacterial AgentsAzithromycinClarithromycincardiovacular complicationscommunity‐acquired pneumoniamacrolides

Identifiers

PMID40481686
PMCPMC12144676

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.