Recognizing that the effects of empiric potassium supplementation might vary by diuretic dose, we wished to examine the effect stratified on diuretic dose. We secondarily examined the effectiveness of empiric potassium supplementation in reducing a composite endpoint of sudden cardiac death/ ventricular arrhythmia to look for mechanistic evidence. Whether this is indicative of the optimal dosage range of empiric potassium supplementation or due to confounding deserves further elucidation. To our knowledge, this is the first study designed to examine the association between empiric potassium supplementation and rates of clinical outcomes in new initiators of loop diuretics. Earlier studies have found no effect of potassium supplementation on the risk of either Foretinib laboratory-defined hypokalemia or clinical outcomes, but these studies examined either thiazide users alone or included together with users of loop diuretics. An additional study examined clinical outcomes associated with baseline potassium use in patients with heart failure, but included patients receiving and not receiving diuretics, did not begin follow-up with the initiation of a diuretic, and did not stratify on diuretic dose. Given that one major mechanism by which potassium may improve survival is reduction in the risk of serious ventricular arrhythmia caused by potassium depletion, it was surprising that potassium did not appear to reduce the risk of SD/VA. However, our finding is consistent with a retrospective analysis of trial data in which potassium supplementation did not affect the incidence of arrhythmic death among persons with left ventricular dysfunction. Strengths of this study include its large sample size, unambiguous primary outcome measure, similarity of compared groups even before matching, restriction to new starters of loop diuretics, examination of empiric rather than reactive potassium supplementation, and stratification by furosemide dose. This study has limitations. First, because of the design, the effect of reactive potassium supplementation was not examined. Second, despite our demonstration of covariate balance between the exposure groupsbothpre-andpost-propensity scoreadjustment,thereexiststhe potential for residual confounding byunmeasured or poorly-measured variables and/or behaviors. In particular, it is possible that persons with mild renal insufficiency may be channeled away from potassium supplementation and may be at higher risk for death than baseline. Arguing against this possibility are findings that mild-to-moderate renal insufficiency may not be an independent risk factor for death. Regardless, we controlled for the presence of diagnosed chronic kidney disease, codes for which may have a sensitivity as high as 80%. Third, we were unable to capture magnesium supplement exposures due to their typical use over-the-counter. An additional limitation includes the potential insensitivity of the SD/VA diagnoses and wide confidence intervals in subgroup analyses. In conclusion, this study provides evidence that the strategy of initiating potassium supplementation together.