The potassium binder patiromer allows continuation of spironolactone, a potassium-sparing diuretic, in patients with advanced chronic kidney disease (CKD) who have resistant hypertension and heart failure, according to the latest analysis of the AMBER trial (NCT03071263).
Of 295 patients in the original trial, 132 (45%) also had heart failure with or without preserved ejection fraction. All patients were randomized to receive either placebo or patiromer (8.4 g once daily) in addition to open-label spironolactone, an aldosterone antagonist (starting at 25 mg once daily), for 12 weeks, along with their usual blood pressure medications. Baseline estimated glomerular filtration rate (eGFR) was 25 to 45 mL/min/1.73 m2 and serum potassium ranged from 4.3 to 5.1 mmol/L.
At 12 weeks, a significantly greater proportion of heart failure patients treated with patiromer than placebo remained on spironolactone therapy: 84.1% vs 68.1%, Patrick Rossignol, MD, PhD, of Lorraine Institute of the Heart and Vessels in France and colleagues reported in the European Journal of Heart Failure. Systolic blood pressure declined 7.8 vs 9.0 mm Hg from baseline, respectively.
Fewer patiromer-treated patients than placebo recipients had serum potassium levels of 5.5 mmol/L or higher: 44% vs 61%, respectively. Nonetheless, the most common reason for spironolactone discontinuation was persistent hyperkalemia (5% vs 4%, respectively). Adverse events were consistent with those observed in the original trial. Gastrointestinal disorders occurred in 11% vs 17%, respectively. Similar proportions of patients with heart failure experienced worsening kidney function as patients without heart failure.
Serum magnesium and calcium largely remained within normal range. (Patiromer releases calcium as it binds potassium in the gastrointestinal tract, and it may bind other cations such as magnesium.)
According to Dr Rossignol’s team, “consistent with the overall AMBER trial, this pre-specified subgroup analysis showed that in a mixed (HFrEF and HFpEF) [heart failure] patient population with resistant hypertension and advanced CKD, concomitant use of patiromer enabled more persistent use of spironolactone by reducing the risk of hyperkalaemia.”
Disclosure: This clinical trial was supported by Relypsa, the makers of patiromer. Please see the original reference for a full list of authors’ disclosures.
Rossignol P, Williams B, Mayo MR, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure [published online May 25, 2020]. Eur J Heart Failure. doi: 10.1002/ejhf.1860