QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis.

RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. STUDY DESIGN: Retrospective observational cohort study using a new-user study design. SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. OUTCOMES: Sudden cardiac death (14 days). ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. LIMITATIONS: Residual confounding. CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.

Duke Scholars

Author Patrick Hank Pun Medicine, Nephrology

Author Sana Mustapha Al-Khatib Medicine, Cardiology