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 chronic kidney disease (CKD), primarily due to hyperkalemia. Methods: AMBER was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study which 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 estimated glomerular filtration rate (eGFR) 25-<30 subgroup. In this subgroup, persistent use of spironolactone was seen in 19/34 (56%) in the placebo group and 27/32 (84%) in the patiromer group (absolute difference 29%, P=0.016). In the eGFR 30-45 subgroup, persistent use of spironolactone was seen in 79/114 (69%) in the placebo group and 99/115 (86%) in the patiromer group (absolute difference 17%, P=0.003). There was no significant interaction between eGFR subgroups (P=0.46). Systolic blood pressure (BP) reduction with spironolactone in the eGFR 25-<30 subgroup was 6-7 mmHg; in the eGFR 30-45 subgroup, it was 12-13 mmHg. 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-<30 subgroup; 53% in the eGFR 30-45 subgroup). Conclusion: Patiromer facilitates the use of spironolactone among patients with rHTN, and its efficacy and safety are comparable in those with eGFR 25-<30 and 30-45 mL/min/1.73m2.