Potassium Supplements With Loop Diuretics May Up Survival

July 16, 2014

PHILADELPHIA, PA — Empiric treatment with potassium supplements was associated with a 7% decline in all-cause mortality (p=0.003) in a matched cohort study of >600 000 patients with a variety of clinical conditions who were initiating therapy with furosemide[1]. The survival benefit reached 16% (p<0.0001) for patients taking the loop diuretic at higher dosages, at least 40 mg/day, observe the authors, led by Dr Charles E Leonard (University of Pennsylvania, Philadelphia) in their report published today in PLoS One.

Potassium supplementation did not show a significant effect either way on the risk of "outpatient-originating" sudden death or ventricular arrhythmias—a finding the authors found "perplexing," Leonard told heartwire . Loop diuretics promote urinary potassium loss, and arrhythmias from hypokalemia are well-recognized potential complications. "So we thought any mortality [reduction] that we could demonstrate would be reflected in a reduced risk of sudden cardiac death or ventricular arrhythmia."

Prophylactic potassium supplementation had been advocated for patients starting loop diuretics, according to Leonard, but its efficacy hasn't been explored in clinical trials, and "more recent clinical opinion suggests that it's probably not the prudent thing to do."

But only about a fourth of the current study's new initiators of furosemide were also prescribed prophylactic potassium, which "I think shows physicians still have a question as to whether it's the appropriate thing to do."

He and his colleagues looked at the effect of prophylactic K supplementation on all-cause mortality and other outcomes in a 1999–2007 Medicaid cohort of 654 060 patients starting on furosemide for the first time. Patients taking K supplements, 27% of the cohort, had to initiate them within a day of starting the diuretic to be included in the analysis.

About three-quarters of the patients had hypertension and many had coronary disease, but Leonard said furosemide was prescribed most often probably for edema associated with heart failure or other conditions. Patients were followed for a maximum of eight years, but most, he noted, had a year or two of data.

Hazard Ratio* (95% CI) for Outcomes for K Supplementation of Furosemide vs No K Supplementation, Stratified by Daily Furosemide Dosage

End points HR (95% CI) p
All-cause mortality 0.93 (0.89–0.98) 0.003
All-cause mortality (<40 mg/d) 0.93 (0.86–1.00) 0.050
All-cause mortality (>40 mg/d) 0.84 (0.79–0.89) <0.0001
Out-of-hospital sudden death or ventricular arrhythmia 1.02 (0.83–1.24) 0.879
*Propensity matching for demographics, whether nursing-home resident, loop-diuretic starting dose, serum potassium during follow-up, any diseases prior to initiation of loop diuretic, drugs ever given for chronic diseases, and oral anticoagulant use

Despite the lack of a significant observed effect of K supplementation on sudden death or ventricular arrhythmias, it remains possible that arrhythmic end points were reduced for patients taking the diuretic at higher dosages. Leonard said the group did a dosage-stratified analysis for the arrhythmic end point, but only 10% of the cohort received furosemide at >40 mg/day, and such events were too few for the results to be meaningful.

He also said it's "fair to question" whether the results are generalizable, characterizing the Medicaid cohort as disadvantaged economically and likely in terms of their healthcare and therefore probably at increased clinical risk overall.

Still, the study fills a knowledge gap unlikely to be addressed in a randomized controlled trial, he observed. No commercial sponsor is likely to come forth to study the two cheap, long-generic agents, and investigators would likely have trouble enrolling the vast numbers of patients needed to show a significant effect.

Leonard reported no conflicts of interest; disclosures for the coauthors are listed in the paper.

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