Rajiv Agarwal1, Patrick Rossignol2, Jeffrey Budden3, Martha R Mayo4, Susan Arthur5, Bryan Williams6, William B White7. 1. Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. 2. University of Lorraine, Inserm 1433 CIC-P CHRU de Nancy, Inserm U1116 and FCRIN INI-CRCT, Nancy, France. 3. Medical Affairs, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California. 4. Biostatistics, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California. 5. Clinical Development, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California. 6. Department of Medicine, Institute of Cardiovascular Sciences University College London and National Institute for Health Research University College London/University College London Hospitals Biomedical Research Centre, London, United Kingdom. 7. Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut.
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.
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.
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