A comparative post hoc analysis of finerenone and spironolactone in resistant hypertension in moderate-to-advanced chronic kidney disease

Abstract

Background: Mineralocorticoid receptor antagonists (MRAs) reduce systolic blood pressure (SBP) and increase serum potassium concentration ([K⁺]). This indirect comparison investigated any differences in SBP-lowering and hyperkalemia risk between finerenone, a nonsteroidal MRA, and the steroidal MRA spironolactone ± a potassium binder.

Methods: In FIDELITY (a pooled analysis of FIDELIO-DKD and FIGARO-DKD), a subgroup of patients with treatment-resistant hypertension (TRH) and chronic kidney disease meeting eligibility criteria of the AMBER trial were identified (FIDELITY-TRH). The main outcomes were mean change in SBP, incidence of serum [K⁺] ≥5.5 mmol/L and hyperkalemia-associated treatment discontinuation. Results at ∼17 weeks were compared with 12 weeks from AMBER.

Results: In 624 FIDELITY-TRH patients and 295 AMBER patients, the least squares mean change in SBP (mmHg) from baseline was -7.1 for finerenone and -1.3 for placebo {between-group difference -5.74 [95% confidence interval (CI) -7.99 to -3.49], P < .0001} versus -11.7 for spironolactone + patiromer and -10.8 for spironolactone + placebo [between-group difference -1.0 (95% CI -4.4-2.4), P = .58]. The incidence of serum [K⁺] ≥5.5 mmol/L was 12% for finerenone and 3% for placebo versus 35% with spironolactone + patiromer and 64% with spironolactone + placebo. Treatment discontinuation due to hyperkalemia was 0.3% for finerenone and 0% for placebo versus 7% for spironolactone + patiromer and 23% for spironolactone + placebo.

Conclusions: In patients with TRH and chronic kidney disease compared with spironolactone with or without patiromer, finerenone was associated with a lower SBP reduction and lower risk of hyperkalemia and treatment discontinuation.Trial Registration: AMBER (NCT03071263), FIDELIO-DKD (NCT02540993), FIGARO-DKD (NCT02545049).

Keywords: finerenone; hyperkalemia; hypertension; patiromer; spironolactone.

Graphical Abstract

Figure 1:

Outcomes for finerenone versus placebo in FIDELITY-TRH and for spironolactone ± patiromer in AMBER. (A) Office SBP, (B) UACR,^a (C) and hyperkalemia outcomes for finerenone versus placebo in the FIDELITY-TRH subgroup (TRH with moderate–advanced CKD population) at ∼17 weeks (120 days) and for spironolactone ± patiromer in AMBER at 12 weeks (serum [K⁺] >5.5 mmol/L). BL, baseline. ^aIn AMBER, the between-group difference for UACR corresponds to the difference between groups [(spironolactone + patiromer) – (spironolactone + placebo)].

Figure 2:

Time to serum [K⁺] ≥5.5 mmol/L in the FIDELITY-TRH and AMBER populations. Time to serum [K⁺] ≥5.5 mmol/L in the (A) FIDELITY-TRH (patients with TRH and moderate–advanced CKD; safety analysis set) and (B) external comparator (AMBER) populations. FIDELITY data (A) are cumulative incidences based on Kaplan–Meier estimates. All interruptions were excluded from the person–time at risk and calculation of relative days, i.e. for patients with an interruption, events in the period from interruption start + 3 days until the end of interruption are not considered. For the external comparator AMBER (B), squares indicate censored observations. Patients who did not have any event were censored on the last date with a serum [K⁺] assessment. Agarwal R, et al. Lancet 2019;394:1540.

Figure 3:

Treatment discontinuation in the FIDELITY-TRH and AMBER populations. (A) Discontinuation due to hyperkalemia and (B) discontinuation for any reason for finerenone versus placebo in the FIDELITY-TRH population (patients with TRH and moderate–advanced CKD) at ∼17 weeks (120 days) versus the external comparator study (AMBER) at 12 weeks.