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Background: While chronic kidney disease (CKD) is common in resistant hypertension (RHTN), prior studies -evaluating mineralocorticoid receptor antagonists excluded patients with reduced kidney function due to risk of hyperkalemia. AMBER (ClinicalTrials.gov identifier NCT03071263) will evaluate if the potassium-binding polymer patiromer used concomitantly with spironolactone in patients with RHTN and CKD prevents hyperkalemia and allows more persistent spironolactone use for hypertension management.Methods: Randomized, double-blind, placebo-controlled parallel group 12-week study of patiromer and spironolactone versus placebo and spironolactone in patients with uncontrolled RHTN and CKD. RHTN is defined as unattended systolic automated office blood pressure (AOBP) of -135-160 mm Hg during screening despite taking ≥3 antihypertensives, including a diuretic, and an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker -(unless not tolerated or contraindicated). The CKD inclusion criterion is an estimated glomerular filtration rate (eGFR) of 25 to ≤45 mL/min/1.73 m2. Screening serum potassium must be 4.3-5.1 mEq/L. The primary efficacy endpoint is the between-group difference (spironolactone plus patiromer versus spironolactone plus placebo) in the proportion of patients remaining on spironolactone at Week 12.Results: Baseline characteristics have been analyzed as of March 2018 for 146 (of a targeted 290) patients. Mean (SD) baseline age is 69.3 (10.9) years; 52.1% are male, 99.3% White, and 47.3% have diabetes. Mean (SD) baseline serum potassium is 4.68 (0.25) mEq/L, systolic AOBP is 144.3 (6.8) mm Hg, eGFR is 35.7 (7.7) mL/min/1.73 m2.Conclusion: AMBER will define the ability of patiromer to facilitate the use of spironolactone, an effective antihypertensive therapy for patients with RHTN and CKD. [ABSTRACT FROM AUTHOR]

Background: Patiromer (PAT) is a sodium-free, non-absorbed potassium (K+) binder approved for the treatment of hyperkalemia (HK). HK is common in older patients (pts) with cardiorenal comorbidities and often limits the use of guideline recommended renin-angiotensin-aldosterone system inhibitor (RAASi) medications. We previously reported the design and results for AMETHYST-DN, a phase 2 multicenter, open-label, 52 week randomized clinical trial in a large cohort of adult pts (n=306; 30-80 years of age). Methods: Here we report the results in a subgroup ≥75 years of age with type 2 DM, chronic kidney disease (CKD) (eGFR 15 to <60 mL/min/1.73 m2), hypertension and serum (s) K+ >5.0 mEq/L (n=60). All pts received a RAASi before and during the study treatment and PAT was titrated to maintain sK+ in the normal range. Results: Two days after the first dose, mean sK+ was reduced to 4.89 mEq/L from a baseline (BL) mean of 5.19 mEq/L (p<0.001). The least square mean reduction in sK+ from BL to week 4 was -0.65 mEq/L (p<0.001) and -0.61 mEq/L (p<0.001) at 52 weeks (end of treatment). The % of pts with sK+ in the normal range (3.8-5.0 mEq/L) between weeks 12-52 ranged from 88-98%. At the end of treatment, 92% of pts had sK+ in the normal range. The most common GI-related adverse event (AE) was constipation observed in 2 pts (3.3%). Serum magnesium levels of <1.2 mg/dL were seen in 3 pts (5%). Hypokalemia (sK+ <3.5 mEq/L) did not occur in this older population. Serious AEs were reported for 9 pts (15%); none attributed to PAT by investigator. Study limitations include a lack of blinding, a lack of comparator, and a lack of diversity. Conclusions: In this subgroup of pts ≥75 years with diabetic CKD receiving a RAASi medication, PAT reduced and maintained control of sK+ for up to 1 year. PAT was well tolerated over 52 weeks with no serious AEs attributed to its use. These results suggest that PAT may facilitate the use of RAASi medications in older pts likely to benefit from their cardiorenal protective effects. Disclosure: G.L. Bakris: Consultant; Self; Merck & Co., Inc., Novo Nordisk Inc., Relypsa, Inc. Research Support; Self; Bayer AG, Janssen Pharmaceuticals, Inc. S.D. Woods: Employee; Self; Relypsa, Inc. P.J. Alvarez: Employee; Self; Relypsa, Inc. J. Fogli: Employee; Self; Relypsa, Inc. S. Arthur: Employee; Self; Relypsa, Inc. M.R. Mayo: Employee; Self; Relypsa, Inc. R. Kumar: None. Funding: Relypsa, Inc. [ABSTRACT FROM AUTHOR]