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.


Share your thoughts on the implications of Dr. Leonard’s study for clinical practice.

4 Responses to “Potassium Supplements for Users of Loop Diuretics?”

  1. i have some submissions regarding this finding,
    1.the daily K+ requirement for an average adult is around 50 meq/ day.

    2.a normal diet supplies around 500 meq/ day of k+.

    3.intact renal function is therefore a must, to maintain critical K+ balance.

    4.Therefore, a supplement of 10 meq/ day, shouldn’t make a big diffrence.

    5.More so, even if effective / statistically significant in those with daily furosemide adminstration >0r = 40 meq/day (in those with intact renal function), i do not see any long term indication of furosemide in such population. On the contrary, decrease in mortality could be due to new intiation of furosemide.

    a full fledged, study needs to be taken up.

    • It is important to know if every patient follows daily a normal diet. My mother-in-law doesn’t and episodically has to take furosemide 40 mg bid or tid. What has saved her is that an smart physician prescribed adding spironolactone at these times, what keeps her K+ reasonable while we beg her to increase bananas and potatoes (she gives us a difficult time with these).

  2. Is it a coincidence that the mainstay of therapies in heart failure (ACE-inhibitors, beta-blockers and MRAs) all tend to increase potassium levels?

  3. izaskun obieta fresnedo, MB, MPH says:

    I agree with Dr Kuchya that it is surprising that a supplement of 10 mEq/day seems a small amount for such a big statistical difference.
    I tend to combine a K+ sparing diuretic (eg MRA) at half dose of furosemide if hypokalaemia is an issue, or if bigger doses of diuretics are needed, as these treatments have shown benefits that may be independent of their K+ sparing capacity