Antibiotic carries short-term increased risk of heart attack, finds ‘persuasive’ study

Researchers observed increased short-term cardiovascular risk among patients taking macrolide antibiotic clarithromycin.

Clarithromycin carries an increased short-term risk of myocardial infarction, arrhythmia and cardiac death and should be prescribed “with caution” to those with a high cardiovascular risk. Pictured, x-ray of the heart suffering from myocardial infarction

Clarithromycin, the macrolide antibiotic commonly prescribed to treat respiratory tract infections, carries an increased short-term risk of myocardial infarction, arrhythmia and cardiac death and should be prescribed “with caution” to patients already at high cardiovascular risk, according to research published in The
on 14 January 2016.

The researchers, led by Ian Wong, head of the research department of practice and policy at UCL School of Pharmacy, London, based their findings on an analysis of more than 320,000 patients in Hong Kong. They did not find any long-term cardiovascular risk associated with the drug.

The researchers analysed cardiovascular outcomes in the Hong Kong population of adults aged 18 years or over between 2005 and 2009 who were prescribed clarithromycin (108,988 patients) or the antibiotic amoxicillin (217,793 patients). The primary outcome they were looking for was myocardial infarction but they also recorded all cardiac or non-cardiac mortality, arrhythmia and stroke.

“No long-term cardiovascular risk was associated with clarithromycin but there was a suggestion of an increased short-term risk of myocardial infarction, arrhythmia and cardiac death associated with current use of clarithromycin among the Hong Kong population,” the researchers say. “Given the acute risk, clarithromycin should be prescribed with caution, especially to patients with a high baseline cardiovascular risk.”

To examine the associations of interest, the authors used three separate study designs — retrospective cohort analysis (with amoxicillin as control), self-controlled case series and case crossover analysis.

Compared with amoxicillin use, use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia and cardiac mortality 14 days after the start of antibiotic treatment (propensity score adjusted rate ratio for myocardial infarction was 3.66; 95% confidence interval 2.82–4.76). Rate ratios for the secondary outcomes increased significantly with current use of clarithromycin versus amoxicillin, except for stroke.

The authors of an accompanying editorial[2]
— Geetha Iyer and G Caleb Alexander, epidemiologists at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland — say that the “strength and consistency of the associations” found in the different study designs are “persuasive and consistent with most of the literature reporting the cardiovascular risks associated with this class of antibiotic”.

But Iyer and Alexander remind clinicians and patients to remember “fundamental concepts of treatment” while trying to make sense of this new evidence.

“All drugs have risks, most drugs have serious risks, and given that as many as a quarter to half of all antibiotics prescribed are not clinically indicated, the opportunities to use these products more judiciously without compromising quality of care are manifold. Clinicians and patients should consider these potentially serious adverse events when prescribing macrolides, especially to those at highest baseline risk,” they add.

Nicola Berns, deputy chief pharmacist and governance and clinical lead at the Queen Elizabeth Hospital King’s Lynn NHS Foundation Trust in Norfolk, echoes these views, pointing out that all prescribing decisions are made on the basis of the relative risks and benefits of treatment.

“Clarithromycin remains an option for the treatment of lower severity community acquired pneumonia (CAP) in patients who are hypersensitive to penicillins and the preferred macrolide choice in combination with amoxicillin or penicillin V for hospitalised patients with moderate to severe CAP,” she says. “Clarithromycin should remain the treatment of choice in these circumstances, but we need to be aware of evidence of the possibility of increased cardiovascular risk.”


[1] Wong AYS, Root A, Douglas IJ et al. Cardiovascular outcomes associated with use of clarithromycin: population based study. The BMJ 2016;352:h6926. doi: 10.1136/bmj.h6926 

[2] Iyer G & Alexander CG. Cardiovascular risks associated with clarithromycin. The BMJ 2016;352:i23. doi: 10.1136/bmj.i23 

Last updated
The Pharmaceutical Journal, PJ, February 2016, Vol 296, No 7886;296(7886):DOI:10.1211/PJ.2016.20200532

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