Hyponatremia almost as common with spironolactone as chlorthalidone

NEW ORLEANS – Spironolactone was almost as likely as chlorthalidone to cause hyponatremia in a review of hypertension patients at the University of Alabama at Birmingham, and prior hyponatremia on chlorthalidone increased the risk.

Dr. Faris Matanes

The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.

Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.

The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.

“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.

Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.

Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.

The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m². Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.

Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.

The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.

Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m², and baseline sodium level 135.8 mEq/L.

All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m²), and were more likely to be white, but the differences were not statistically significant.

There was no external funding, and the investigators didn’t have any industry disclosures.

aotto@mdedge.com

SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.