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BOSTON -- New therapeutic agents including patiromer (Veltassa) and sodium zirconium cyclosilicate (ZS-9; Lokelma) appear effective in reducing serum potassium levels, but more research is needed to evaluate long-term cardiovascular outcomes, a systematic review found.

At one month follow-up, patiromer had lowered serum potassium by 0.65 to 1.01 meq/L in data from three trials. Common adverse events were diarrhea, constipation, and hypomagnesemia hypokalemia, reported Sankar Dass Navaneethan, MS, MPH, MBBS, of the Baylor College of Medicine in Houston, and a colleague here at the .

In three other trials involving ZS-9, the drug had lessened serum potassium by similar magnitudes at 48 hours. The effect continued for up to one month in one of those studies, the researchers found.

ZS-9 was also associated with fewer electrolyte abnormalities and gastrointestinal side effects, although investigations showed greater incidence of edema than placebo.

But long-term outcomes related to cardiovascular events and death with both drugs remain uncertain, the researchers stressed.

This investigation demonstrates the need for further research "to see if use of these agents would help us continue use [of] angiotensin-converting-enzyme inhibitor/angiotensin II receptor blockers and in turn offer renoprotective and cardiac benefits," emphasized Navaneethan.

"Newer agents lower serum potassium in those with hyperkalemia and other comorbid conditions such as heart failure and kidney disease and could be considered in appropriate clinical setting. The adverse effect profile seems to differ and has to be considered while using these agents," Navaneethan told 番茄社区app.

Patiromer was first approved in the U.S. in late 2015; ZS-9 got the FDA's OK .

The investigators assessed six clinical trials involving these agents with a total of 1,756 participants. Their mean age was 65. Comorbidities including congestive heart failure, chronic kidney disease, diabetes mellitus, and hypertension were common.

The researchers used MEDLINE to gather randomized controlled clinical trials comparing patiromer and ZS-9 to placebo or other active interventions to reduce serum potassium. Outcome measures including adverse events and declines in serum potassium levels at various time points were considered. Risk bias of the included investigations were evaluated using the Cochrane Collaboration tool.

Navaneethan acknowledged limitations of the review, including that the investigators were unable to perform a full meta-analysis with pooled data "due to the heterogeneous nature of these trials -- study population and study duration differed among included studies."

"Current clinical trial evidence demonstrate the potassium lowering potential of newer therapeutic agents and their differential side effects. However, whether this translates to reducing long term cardiovascular and mortality risk, continuation of renin angiotensin blockers to reduce kidney disease progression warrant further studies," the researchers concluded.

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