Clin Transl Sci. 2022 Aug 15. doi: 10.1111/cts.13377. Online ahead of print.
ABSTRACT
This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+ ) in patients with heart failure (HF) with preserved or mildly reduced EF (≥ 40%), and renal impairment. HF patients with EF ≥ 40% and estimated glomerular filtration rate of 40-70 mL/min/1.73 m2 were randomized to once-daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up-titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days. Primary endpoint was relative change (%) in sK+ for AZD9977 versus spironolactone (baseline to Day 28). Serum/urinary electrolytes, fractional excretion (FE) of Na+ /K+ , plasma aldosterone, cortisol and renin, and safety were also assessed. Sixty-eight patients were randomized (AZD9977, n = 33; spironolactone, n = 35). Mean (SD) age was 73.0 (8.5) years, 51.5% male. Mean sK+ change from baseline to Day 28 was 5.7% (AZD9977) and 4.2% (spironolactone), and 1.5% and 4.2% at Day 14. Relative change (95% CI) in sK+ with AZD9977 versus spironolactone was -0.3% (-5.3% – 4.4%; Day 28), and 3.4% (-0.8% – 7.5%; Day 14). Median increase from baseline in plasma aldosterone at Day 28 was 89.8 pmol/L for AZD9977 and 67.4 pmol/L for spironolactone. Median FE of K+ was 12.9% (AZD9977) and 10.1% (spironolactone). AZD9977 was well tolerated. No discontinuations due to hyperkalemia occurred with either treatment. Evidence of target engagement for AZD9977 with a favorable safety profile, supports further evaluation of AZD9977 in patients with HF and renal impairment.
PMID:35971596 | DOI:10.1111/cts.13377
