Novel therapies target hyperkalemia, improve use of RAAS inhibitors

BOSTON — Hyperkalemia occurs frequently in patients with chronic kidney disease and HF, and is also a common complication of renin-angiotensin-aldosterone inhibitor use. However, newer therapies can effectively and rapidly reduce potassium levels, according to a presenter at the Cardiometabolic Health Congress.

Rajiv Agarwal, MD, professor of medicine at Indiana University School of Medicine, said many studies show a significant relationship between mortality and both low and high potassium levels, and that risk grows in patients who have hyperkalemia but no kidney disease.

Agarwal cited a 2009 retrospective study published in Archives of Internal Medicine that analyzed a national cohort of more than 2 million records from 245,808 veterans with at least one hospitalization and at least one inpatient or outpatient serum potassium record during 2005. The researchers looked at rate of death within 1 day of a hyperkalemic event as the principal outcome. They found that, while the risk for hyperkalemia increased with chronic kidney disease (CKD), the adjusted odds of death from a moderate and severe hyperkalemic event was higher in patients without CKD.

“Hyperkalemia is a harbinger of death … especially in an individual with no prior kidney disease,” Agarwal said during a presentation. “Even mild hyperkalemia is also associated with a 10-fold higher risk of death compared with no hyperkalemia. So, even a trivial increase in potassium comes with a large risk in mortality.”

The major risk with hyperkalemia is that RAAS inhibition cannot be used effectively, Agarwal said.

“All these studies put together suggest that we are limited in our ability to use RAAS blockade in the long term because of the frequency of hyperkalemia, which frequently necessitates either interruption or stoppage of these therapies to allow potassium to come back to normal [levels], and perhaps that’s not so good for the patients,” Agarwal said.

Strategy to reduce potassium levels

When a patient presents with hyperkalemia, Agarwal recommended that several steps be taken: estimate glomerular filtration rate; stop the offending agents, including, often, certain NSAIDs; and put the patient on a low-potassium diet.

“You might have to use thiazide or a loop diuretic, and sometimes in combination,” Agarwal said. “It might not be appropriate for everyone, but it will get the potassium down.”

Correcting metabolic acidosis with a half teaspoon of baking soda, lowering the dose of ACE inhibitor or angiotensin receptor blocker therapy, and avoiding spironolactone if the estimated GFR is less than 30 are additional measures that can be taken, he said.

New treatment options

Newer therapies promise to change the picture, Agarwal said.

Patiromer (Veltassa, Relypsa), a potassium-binding agent approved by the FDA this week, is the first medication approved to treat hyperkalemia in more than 50 years. In the phase 3 OPAL-HK study, the drug decreased potassium levels in patients with CKD who were taking RAAS inhibitors compared with patients assigned a placebo.

An additional therapy, sodium zirconium cyclosilicate (ZS-9, ZS Pharma), was also associated with rapid and sustained reductions in serum potassium compared with placebo in patients with hyperkalemia, Agarwal said, and is currently pending FDA approval. – by Regina Schaffer

Reference:

Agarwal R. Addressing the unmet need in hyperkalemia treatment. Presented at: Cardiometabolic Health Congress; Oct. 21-24, 2015; Boston.

Disclosure: Agarwal reports consulting agreements or receiving research funding or honoraria from Abbvie, Amgen, Ardelyx, Bayer, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Reata, Relypsa, Roche, Sandoz, Sigma Tau, Takeda and ZS Pharma.