Concerns about hyperkalemia may lead clinicians to underuse mineralocorticoid antagonists [MRAs] in hospitalized patients with heart failure, according to new study finding published in JACC: Heart Failure. This practice, however, may be associated with higher risk of patient death.

In PROTECT [Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function] trial, 1589 patients had mild to moderate renal impairment (estimated creatinine clearance: 20 to 80 mL/min) and serum potassium of 3.5 mEq/L or greater (or 3.0 to 3.5 mEq/L if potassium was given parenterally) upon admission. Incident hyperkalemia (serum potassium exceeding 5.0 mEq/L) developed in a third of patients during hospitalization.

Hyperkalemic patients were more often taking MRAs prior to hospitalization (53% vs 44% vs 35% of normokalemic and hypokalemic patients, respectively). They were also more likely to have MRAs down-titrated during hospitalization (15% vs 9% vs 8%, respectively).

Continue Reading

Hyperkalemia was not associated with adverse outcomes. But down-titration of MRAs during hospitalization was independently associated with a 73% increased risk for 180-day mortality, investigators led by Peter van der Meer, MD, PhD, of the University Medical Center Groningenin in the Netherlands, reported. In contrast, hyperkalemic patients discharged with the same or higher dose of MRAs or angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) had lower risks for early death. Treatment with rolofylline had no effect on mortality, according to the investigators.

“Survival analyses indicated that patients still benefit from constant doses or up-titration of MRAs and/or ACE inhibitors/ARB, despite incident hyperkalemia, in a clinical setting,” Dr van der Meer’s team concluded.

Related Articles


Beusekamp JC, Tromp J, Cleland JGF, et al. Hyperkalemia and treatment with RAAS-inhibitors during acute heart failure hospitalizations and their association with mortality [published online October 5, 2019]. JACC: Heart Failure. doi:10.1016/j.jchf.2019.07.010