Azithromycin appears to significantly increase patients’risk for sudden cardiac death compared with patients taking no antibiotics,results of an analysis reveal.

The hazard ratio for cardiovascular death during a five-daycourse of azithromycin, a macrolide antibiotic, was 2.88 (95% CI: 1.79- 4.63; P<0.001),Wayne A. Ray, PhD, of Vanderbilt University in Nashville, and colleaguesreported in the New England Journal of Medicine.

Risk for cardiovascular death with azithromycin was alsoelevated (HR=2.49; 95% CI: 1.38-4.50; P=0.002) when comparedwith amoxicillin, another common antibiotic.

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The FDA has announced that it is reviewing the results ofthe study and will communicate any new information about the azithromycin andrisk for sudden cardiac death after the review is complete.

In the meantime, patients “should not stop taking theirmedicine without talking to their healthcare professional,” the agency stated.The FDA advises health-care providers to “be aware of the potential for QTinterval prolongation and heart arrhythmias,” when prescribing the medication.

The macrolides clarithromycin and erythromycin are known toincrease the risk for adverse cardiovascular events including ventricular arrhythmiasand sudden cardiac death, but azithromycin had not previously been associatedwith heart risks.

Recently, reports of arrhythmia-related adverse cardiacevents with azithromycin have been noted. At least 20 instances of torsades depointes have been recorded in the FDA’s Adverse Event Reporting System,according to background information in the article.

To further examine this trend, Ray and colleagues analyzedcardiovascular and all cause mortality among patients in the Tennessee Medicaidprogram between 1992 and 2006.

The researchers looked at deaths among patients givenazithromycin and compared them to those that occurred among matched controlsnot given antibiotics, those treated with amoxicillin, ciprofloxacin andlevofloxacin. Amoxicillin and ciprofloxacin have little to no cardiovascularhazard, whereas levofloxacin is thought to be pro-arrythmogenic. 

There were 347,795 prescriptions for azithromycin, 1,348,672for amoxicillin, 264,626 for ciprofloxacin, and 193,906 for levofloxacin duringthe study period. A total of 1,391,180 controls not given antibiotics wereincluded.

The researchers observed 29 cardiovascular deaths during thefive-day course of azithromycin, 22 of which were sudden cardiac deaths.

This equates to a rate of 85.2 cardiovascular deaths and64.6 sudden cardiac deaths per 1 million courses of azithromycin. During thecontrol period, rates among those not given antibiotics were 29.8 and 24,respectively, the researchers found.

Compared with patients not given antibiotics, all causemortality was also up in patients taking azithromycin (HR=1.85; 95% CI: 1.25-2.75; P=0.002).

Compared with patients assigned to a five-day course ofamoxicillin, those taking azithromycin had increased risk for bothcardiovascular (HR 2.49, 95% CI 1.38 to 4.50, P=0.002) and all causemortality (HR 2.02, 95% CI 1.24 to 3.30, P=0.005), the researchersfound.

There was a significantly increased risk of cardiovasculardeath for azithromycin versus ciprofloxacin (HR=3.49; 95% CI: 1.32- 9.26; P=0.01),but there was no significant difference between azithromycin and levofloxacin.

This equates to an estimated 47 additional cardiovasculardeaths per 1 million 5-day courses of azithromycin therapy. Among patients inthe highest decile of cardiovascular risk at baseline, the were an estimated245 additional cardiovascular deaths per million courses, the researchers determined.

“Duringfive days of azithromycin therapy, there was a small absolute increase incardiovascular deaths, which was most pronounced among patients with a highbaseline risk of cardiovascular disease,” the researchers concluded.

RayW et al. N Engl J Med. 2012;366:1881-1890.