August 11th, 2014
Potassium Supplements for Users of Loop Diuretics?
Dr. Behnood Bikdeli interviews Dr. Charles E. Leonard about his study, recently published in PLOS ONE, investigating possible survival benefits from the empiric use of potassium supplements in new users of loop diuretics.
Bikdeli: This is a very interesting exploratory analysis. Please share the key findings.
Leonard: Despite the sound theoretical basis for empirical K+ supplementation in new initiators of furosemide, we were aware of no previous studies examining whether this practice improves survival. Our retrospective cohort study, nested within a Medicaid population, has shown that empiric K+ supplementation appeared to reduce mortality risk by 7% in patients who received furosemide at a dose of <40 mg/day and by 16% in patients who received ≥40 mg/day of furosemide. These are clinically important yet plausible improvements in survival.
Bikdeli: In your study, did any specific factors affect the potential benefit of potassium supplementation?
Leonard: In preplanned analyses examining potential effect modification, we investigated the association between empiric K+ supplementation and mortality in analyses that were stratified by age; K+ supplement dose; the presence of a preexisting arrhythmia; and the presence of preexisting kidney disease. Among patients receiving <40 mg/day of furosemide, the effect of K+ supplementation did not differ by subgroup. Among patients receiving ≥40 mg/day of furosemide, we saw a numerical (but not a statistically significant) difference by preexisting kidney disease status, suggesting that the survival benefit was limited to patients without kidney dysfunction. Furthermore, among patients receiving ≥40 mg/day of furosemide, the improvement in survival appeared to be greatest for persons treated with K+ ≤10 mEq/day. Although that finding was statistically significant, we hesitate to interpret this as the optimal dose threshold for empiric K+ supplementation, as our propensity-score matching was not designed to balance covariates within K+ dose strata.
Bikdeli: You report an impressive number needed to treat of 67, to prevent one death within the first year after supplementation. What should be the next step for widespread change in clinical practice? Millions of patients take loop diuretics, and potassium supplements are cheap and easy to find. Might a “pragmatic trial” follow soon?
Leonard: Prior to our study, the clinical question of whether or not to empirically supplement new furosemide users with K+ was based on expert opinion without explicit critical appraisal (Oxford Centre for Evidence-Based Medicine level of evidence = 5). Our study has provided individual cohort study data, raising the evidence level to 2. Nevertheless, this study deserves independent replication before being incorporated into practice guidelines.
It would be nice to see a pragmatic trial, as it would indeed provide useful data on the effectiveness of this K+ supplementation strategy. Such a trial would probably be simpler and cost less than the corresponding explanatory trial. Pragmatic trials, though, are not without limitations; these would need to be kept in mind when interpreting data from such a study.
Bikdeli: Until more data emerge, would you change your practice in any way as a result of this study?
Leonard: Given the sound theoretical basis for empiric K+ supplementation in a population without kidney disease, I think it would be reasonable to consider these data as applicable to practice. Notably, though, the clinician should always consider individual patient factors in arriving at treatment decisions.
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Share your thoughts on the implications of Dr. Leonard’s study for clinical practice.