Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial

Abstract

Background: Mineralocorticoid receptor antagonists reduce mortality in patients with heart failure with reduced ejection fraction and have become a standard of care in those with resistant hypertension (rHTN). Yet, their use is limited among patients with CKD, primarily due to hyperkalemia.

Methods: AMBER was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that reported that the use of the potassium-binding drug patiromer allowed a more persistent use of spironolactone in patients with CKD and rHTN. In this report, we compare the safety and efficacy of patiromer in advanced CKD as a prespecified analysis.

Results: Of the 295 patients randomized, 66 fell into the eGFR 25 to <30 subgroup. In this subgroup, persistent use of spironolactone was seen in 19 of 34 (56%) in the placebo group and 27 of 32 (84%) in the patiromer group (absolute difference 29%; P<0.02). In the eGFR 30-45 subgroup, persistent use of spironolactone was seen in 79 of 114 (69%) in the placebo group and 99 of 115 (86%) in the patiromer group (absolute difference 17%; P=0.003). There was no significant interaction between eGFR subgroups (P=0.46). Systolic BP reduction with spironolactone in the eGFR 25 to <30 subgroup was 6-7 mm Hg; in the eGFR 30-45 subgroup, it was 12-13 mm Hg. There was no significant interaction between eGFR subgroups on BP reduction (P=0.79). Similar proportions of patients reported adverse events (59% in the eGFR 25 to <30 subgroup; 53% in the eGFR 30-45 subgroup).

Conclusions: Patiromer facilitates the use of spironolactone among patients with rHTN, and its efficacy and safety are comparable in those with eGFR 25 to <30 and 30-45 ml/min per 1.73 m2.

Clinical trial registry name and registration number: Clinicaltrials.gov, NCT03071263.

Keywords: chronic kidney disease; chronic renal insufficiency; hyperkalemia; patiromer; resistant hypertension; spironolactone.

Conflict of interest statement

R. Agarwal reports personal fees from Akebia, AstraZeneca, Bayer, Boehringer Ingelheim, Diamedica, Eli Lilly, Johnson & Johnson, Merck, Reata, Relypsa, Inc., a Vifor Pharma Group Company, and Sanofi; has served as an associate editor of the American Journal of Nephrology and Nephrology Dialysis and Transplantation; is an author on UpToDate; and received research grants from the National Institutes of Health and the US Veterans Administration. S. Arthur reports employment by Relypsa, Inc., a Vifor Pharma Group Company, and stock in Vifor Pharma. J. Budden reports employment by Relypsa, Inc., a Vifor Pharma Group Company, and stock in Vifor Pharma. M. R. Mayo reports previous employment by Relypsa, Inc., a Vifor Pharma Group Company, during the time of the study. P. Rossignol reports consulting for G3P and Idorsia; received honoraria from Ablative Solutions, AstraZeneca, Bayer, Boehringer-Ingelheim, Corvidia, CVRx, Fresenius, Grunenthal, Novartis, NovoNordisk, Relypsa, Inc., a Vifor Pharma Group Company, Sequana Medical, Servier, Stealth Peptides, and Vifor Fresenius Medical Care Renal Pharma; received travel grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma; and is a cofounder of CardioRenal. B. Williams reports honoraria for lectures on hypertension from Boehringer Ingelheim, Daichii Sankyo, Novartis, Pfizer, and Servier and consulting for Novartis, Relypsa, Inc., a Vifor Pharma Group Company, and Vascular Dynamics Inc. W. B. White has nothing to disclose.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Percentage of patients who remained on spironolactone at week 12 by eGFR subgroup. 95% CI, 95% confidence interval.

Figure 2.

Time to discontinuation of spironolactone (Spiro) in patients. (A) the eGFR 25 to <30 subgroup and (B) the eGFR 30–45 subgroup. Discontinued patients indicate the numbers of patients who discontinued study treatment early for hyperkalemia (HK) or other reasons prior to or at a study visit. PAT, patiromer; PBO, placebo.

Figure 3.

Time to first serum potassium value ≥5.5 mEq/L during treatment in patients. (A) the eGFR 25 to <30 subgroup and (B) the eGFR 30–45 subgroup. The Kaplan–Meier (product-limit) estimates are shown. The number of patients at risk at each time point is the number of patients on treatment and still without event at the end of the time point. The patients who completed 12 weeks of study treatment and had not had any event are censored at week 12. PAT, patiromer; PBO, placebo; Spiro, spironolactone.

Figure 4.

Least squares (LS) mean (SEM) systolic automated office BP (AOBP) change from baseline to week 12 by eGFR subgroup. 95% CI, 95% confidence interval; PAT, patiromer; PBO, placebo; Spiro, spironolactone.