Antibiotic raises cardiac mortality risk
MedWire News: The broad-spectrum macrolide antibiotic azithromycin is linked to a small increase in cardiovascular (CV) mortality, which is most pronounced among patients with a high baseline CV disease (CVD) risk, a study shows.
The findings, reported in TheNew England Journal of Medicine, arise in the light of previous studies that showed azithromycin may have proarrhythmic effects, including pronounced QT-interval prolongation, torsades de pointes, and polymorphic ventricular tachycardia.
Wayne Ray (Vanderbilt University, Nashville, Tennessee, USA) and team studied a Tennessee Medicaid cohort that was designed to detect an increased risk for mortality related to short-term cardiac effects of medication, excluding patients with serious non-CV related illness and person-time during and shortly after hospitalization.
The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score-matched individuals who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).
During 5 days of therapy, patients who took azithromycin had a 2.88-fold higher risk for CV mortality, and a 1.85-fold higher risk for death from any cause than those who took no antibiotics (p<0.002).
Patients who took amoxicillin had no increase in the risk for mortality during this period.
Patients who took azithromycin had a 2.49-fold higher risk for CV death and 2.02-fold higher risk for death from any cause than those who took amoxicillin (p<0.005), with an estimated 47 additional CV deaths per 1 million courses.
The researchers calculated a risk score for CVD that estimated the probability of a CVD death (in the absence of use of a study antibiotic) as a function of the indicators of coexisting conditions.
Based on this, they found that patients in the highest decile of risk for CVD had an estimated 245 additional CV deaths per 1 million courses compared with those in the lowest decile.
A 5-day azithromycin course was associated with a 3.49-fold higher risk for CV death than a 5-day ciprofloxacin course. However, risk for CV death did not differ significantly between azithromycin- and levofloxacin-treated patients.
The authors say the results of the study must be interpreted in light of potential confounders, including CVD and other coexisting conditions, behavioural risk factors associated with CVD, and indication for antibiotic therapy.
By Piriya Mahendra