Macrolide exposure influences risk for cardiac death, arrhythmia

The use of macrolide antibiotics may be associated with a minor increase in the risk for sudden cardiac death or ventricular tachyarrhythmias, according to the results of a recently published meta-analysis.

“The absolute risks of sudden cardiac death [SCD] and cardiac death are small, so it should likely have a limited effect on prescribing practice,” Su-Hua Wu, MD, PhD, of the cardiology department at the First Affiliated Hospital at Sun Yat-Sen University, Guangzhou, China, said in a press release. “However, given that macrolides are one of the most commonly used antibiotic groups and millions of patients are prescribed these drugs annually, the total number of sudden cardiac deaths or ventricular tachyarrhythmias [VTA] and cardiac deaths may not be negligible.”

Wu and colleagues retrospectively examined a sample of 33 published studies involving almost 21 million participants. Potential studies were identified through unrestricted searches of the MEDLINE and EMBASE databases using keywords related to oral macrolide antibiotics and serious cardiac events, and were only included in the analysis if RR and measure of uncertainty were reported. The primary endpoints were SCD or VTA, and the secondary outcome was CV death and all-cause mortality.

Statistical analysis of the pooled data revealed an increased risk of SCD or VTA (RR = 2.42; 95% CI, 1.61-3.63) among patients taking macrolides. Similar increases were seen when examining SCD alone (RR = 2.52; 95% CI, 1.91-3.31) and cardiovascular death (RR = 1.31; 95% CI, 1.06-1.62). No relationship, however, was seen between macrolide antibiotic use and all-cause death or any CV events. Risk increases varied between macrolide types, with the exception of roxithromycin.

These findings translate to an estimated absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional CV deaths per 1 million treatment courses, the researchers wrote.

“Results of this meta-analysis suggest that macrolides may be associated with significant increased risk for SCD or VTA and cardiovascular death but not for all-cause mortality,” the investigators wrote. “This calls for large well-designed [randomized controlled trials] to further elucidate the CV safety of macrolides.”

In a related editorial, Sami Viskin, MD, of the Tel Aviv Sourasky Medical Center and Sackler School of Medicine at Tel Aviv University, Israel, and colleagues wrote that “drug-induced arrhythmia” has been a continuing issue for the pharmaceutical industry for decades. They advocated for further research toward the identification of potential risk factors, and argued that the issue should not be ignored by the field.

“The 1:30,000 iatrogenic arrhythmia death risk reported by Cheng et al. cannot be simply swept under the carpet,” they wrote. “Given the omnipresence of practice guidelines issued by authoritative organizations dealing with just about every topic in cardiology, it is time for a consensus paper on how to deal with these controversies.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

References:

Cheng Y-J, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2015.09.029.

Viskin S, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2015.09.027.