NEW YORK CITY, NY — A small retrospective analysis assessing the safety of spironolactone in patients with resistant hypertension suggests that hyperkalemia occurs not infrequently and that further studies are needed to assess the safety of the drug in these difficult-to-treat patients[1].

"For initial treatment, the hypertension guidelines recommend the more common blood-pressure–lowering agents, like ACE inhibitors, angiotensin-receptor blockers, and diuretics," senior investigator Dr Joel Marrs (University of Colorado, Aurora) told heartwire . "A lot of the benefit of spironolactone, where it's been studied, is as the fourth agent, and there are data showing a pronounced lowering of blood pressure when it's added. We're seeing it used more and more in resistant hypertension, so we wanted to assess the safety of spironolactone, given that the way it works you can actually see an increase in potassium levels."

Marrs presented the data here at the American Society of Hypertension (ASH) 2014 Annual Scientific Meeting .

Effective, but Raises Potassium Levels

As reported previously by heartwire , adding spironolactone to three antihypertensive medications in patients with resistant hypertension resulted in statistically significant reductions in systolic blood pressure. In this European study, adding spironolactone reduced daytime and nighttime systolic blood pressure, assessed by ambulatory blood-pressure monitoring (ABPM), by approximately 9 mm Hg.

The main concern with elevated potassium levels is the onset of arrhythmias, said Marrs. He noted that the Randomized Aldactone Evaluation Study (RALES) showed a statistically significant threefold increased risk in hospitalizations related to hyperkalemia in patients with heart failure who received spironolactone and an ACE inhibitor. Hyperkalemia is defined as a potassium level >5.5 mmol/L.

In this latest study of 73 individuals with resistant hypertension treated with spironolactone, the incidence of hyperkalemia was 8.2%. Four patients stopped taking the drug because of elevated potassium levels, and one patient developed hyperkalemia that resulted in a visit to the emergency department. Two patients experienced an increase in potassium >2.0 mmol/L from baseline (both of whom developed hyperkalemia), but the average increase in potassium levels among the 73 patients was 0.2 mmol/L.

Patients with compromised renal function, those with an estimated glomerular filtration rate (eGFR) <60 mL/min, were more likely to develop hyperkalemia than those with healthier kidneys.

Marrs said their goal is to ensure patients are adequately monitored when spironolactone is added and recommends physicians check potassium levels within a week or two after initiating therapy. "A lot of this paper is to remind doctors to be cognizant," said Marrs. "If you are going to use the drug, you need to be aware of the patient's baseline potassium levels, their baseline renal function, and also what other drugs they might be on that raise potassium levels."


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