Impact of empiric potassium supplementation on mortality, sudden cardiac arrest and stroke in furosemide initiators

AIM: A prior non-randomized study suggests that potassium supplementation may improve survival among furosemide initiators, and a randomized trial suggests that salt substitutes containing potassium might lower stroke risk. We conducted a retrospective cohort study using health-care data to confirm or refute these associations among new users of furosemide. METHODS: The exposure of interest was empiric potassium dispensing (yes/no) concurrent with furosemide initiation. Outcomes were all-cause mortality, sudden cardiac arrest/ventricular arrhythmia (SCA/VA), and stroke. Primary as-started and secondary as-treated analyses were performed with Cox proportional hazards regression. We used inverse probability of treatment weighting (IPTW) to control for confounding, with weights calculated from high-dimensional propensity scores. RESULTS: We identified 511 462 and 320 703 initiators of furosemide <40 and ≥40 mg/day with 21.5% and 35.3%, respectively, starting empiric potassium supplementation. In initiators of furosemide <40 mg/day with (vs. without) empiric potassium, as-started IPTW-hazard ratios (HRs) were 1.02 (95%CI 1.01-1.04) for death, 1.00 (0.94-1.04) for SCA/VA, and 1.03 (1.00-1.06) for stroke. Similarly, in initiators of furosemide ≥40 mg/day with (vs. without) empiric potassium, as-started IPTW-HRs were 1.02 (1.00-1.03) for death, 0.98 (0.94-1.03) for SCA/VA, and 1.01 (0.98-1.04) for stroke. CONCLUSION: We did not observe associations suggesting a clinically meaningful effect of empiric potassium supplementation among furosemide users. However, given the high prevalence of furosemide use among highly heterogeneous patient populations, a large pragmatic trial may be warranted to more definitively evaluate the potential benefits and harms of empiric potassium supplementation among furosemide initiators.