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Abstract
Objective To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics.
Design Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication.
Setting Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES).
Participants Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES.
Main outcome measures The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality.
Results Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22.
Conclusions CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics.
- respiratory tract infection
- antibiotics
- clarithromycin
- mortality
- arrhythmia
- Cardiovascular event
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Footnotes
Contributors CJC and CAB developed the study protocol. Data extraction and analysis were carried out by BJ, EB and SJ-J, supervised by CJC. CCB advised on the interpretation of the study findings. CAB and MO provided statistical expertise. HdV, EB and SJ-J contributed to the writing of the manuscript. Owing to the conditions of the data license, co-authors from the funding body did not have access to the source CPRD data. However, they did have access to processed data. All other authors had full access to all of the data (including statistical reports and tables) in the study. All authors contributed to, read and approved the final manuscript, and all authors take responsibility for the integrity of the data and the accuracy of the data analysis. CJC is the guarantor, had final responsibility for the decision to submit for publication, and takes overall responsibility for all aspects of the study and this manuscript.
Funding This study was supported by Abbott Healthcare Products (Mylan since February 2015), producers of branded clarithromycin in developed markets. This article has been reviewed for scientific content by the former Abbott (now Mylan) employees Mario Ouwens and Hans Friedrich Koch, and one employee HdV contributed to the writing.
Competing interests All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) CAB is a contractor of, EB, BJ and SJ-J are employed by, and CJC is a director of Pharmatelligence, a research consultancy receiving funding from Mylan for the submitted work; (2) HdV is employed by, and MO was employed at time of writing by Mylan. Mario Ouwens was an employee of Mylan at time of writing, however, is now an employee of Astra Zeneca.
Ethics approval Studies using the CPRD are covered by ethics approval granted by the Trent Multicentre Research Ethics Committee (reference 05/MRE04/87). This study was granted CPRD Independent Scientific Advisory Committee approval on 26 March 2015, protocol number 15_012R2.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.