Patiromer, a potassium binder approved for the treatment of hyperkalemia, enables longer use of spironolactone in patients with chronic kidney disease (CKD) regardless of diabetes status, according to a recent subgroup analysis of the AMBER trial.

The trial included 295 patients with CKD and resistant hypertension despite taking 3 or more antihypertensive drugs. Investigators randomly assigned patients to receive open-label oral spironolactone 25 mg once daily and, in double-blind fashion, either patiromer 8.4 g once daily or placebo.

In the original AMBER analysis, 66% of patients in the placebo group and 86% in the patiromer group remained on spironolactone at week 12, the primary study endpoint. In the diabetes subgroup, 65.3% of patients receiving placebo remained on spironolactone at week 12 compared with 83.6% receiving patiromer, Rajiv Agarwal, MD, of Indiana University and the Richard L. Roudebush VA Medical Center in Indianapolis, and colleagues reported in the Clinical Journal of the American Society of Nephrology. In the subgroup without diabetes, 67.1% of patients receiving placebo remained on spironolactone at week 12 compared with 87.8% receiving patiromer. Serum potassium levels of 5.5 mEq/L or higher occurred in a significantly higher proportion of the placebo group compared with the patiromer group among those with diabetes (72% vs 41%) and those without diabetes (56.6% vs 29.7%).

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‘No Surprises’

“There were no surprises here. This was a more granular look at the original study,” Dr Agarwal said.

He also observed, “Patiromer is the only sodium-free potassium binder approved in the United States and may be an agent of choice for patients with resistant hypertension that may be more sensitive to sodium.”

In the current analysis, the subgroup of 150 patients without diabetes included 76 in the placebo arm and 74 in the patiromer arm. The subgroup of 145 patients with diabetes included 72 in the placebo arm and 73 in the patiromer arm.

In patients with diabetes, patiromer’s safety profile was consistent with previous reports. The authors noted that spironolactone is recommended in patients with resistant hypertension, including those with diabetes. Still, there are concerns that spironolactone may increase hyperkalemia risk, thus limiting its use in patients with diabetes.

Adverse events (AEs) occurred in about 60% of patients with diabetes and 61% of placebo recipients, and 60% of patiromer-treated patients. Serious AEs occurred in 3 placebo recipients and 1 patiromer-treated patient.

Cardiovascular Outcomes Unclear

Dr Agarwal noted that it remains unclear whether the enabling of spironolactone use with patiromer leads to improved cardiovascular outcomes. “We need hard outcomes but I don’t know if we will get that. We need to look at survival and hospitalization,” Dr Agarwal said. “We need to know if you can prevent hospitalizations and heart attacks.”

Nephrologist Matthew B. Rivara, MD, an assistant professor of medicine in the division of nephrology at the University of Washington and Harborview Medical Center in Seattle, said the new findings are an important contribution to the literature given the challenges in treating resistant hypertension in patients with diabetes and co-existing CKD. “These findings may encourage more nephrologists and other treating clinicians to consider treating patients with resistant hypertension with spironolactone, despite coexisting CKD and diabetes,” Dr Rivara said.

Many physicians are reluctant to use mineralocorticoid receptor antagonists (MRAs) such as spironolactone in patients with diabetes and/or CKD due to the risk of hyperkalemia, he said. There is an urgent need to determine the long-term benefits of prolonging spironolactone use with patiromer, “particularly with new clinical practice guidelines advocating lower blood pressure targets for patients with chronic kidney disease,” Dr Rivara said. “There is a need for more tools to be able to treat hypertension in these patients. Use of a potassium binding resin like patiromer in conjunction with an MRA is one such tool.”

Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center and chief of Research and Education Service at Veterans Affairs in St. Louis, Missouri, said that while adding patiromer to control potassium may enable use of spironolactone, clinicians need to look at it from a patient perspective because it adds to patients’ pill burden. “There is also the issue of cost, which for some patients may be a serious problem. Also very importantly, there is the question of whether this practice leads to improved outcomes and if so at what cost in terms of adverse events and economic costs,” Dr Al-Aly said.


Agarwal R, Rossignol P, Mayo, M, et al. Patiromer to enable spironolactone in patients with resistant hypertension and chronic kidney disease (AMBER). Clin J Am Soc Nephrol. Published online June 23, 2021. doi:10.2215/CJN.02890221