Dataset Information

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).

SUBMITTER: Agarwal R

PROVIDER: S-EPMC9972517 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Agarwal Rajiv R Pitt Bertram B Palmer Biff F BF Kovesdy Csaba P CP Burgess Ellen E Filippatos Gerasimos G Małyszko Jolanta J Ruilope Luis M LM Rossignol Patrick P Rossing Peter P Pecoits-Filho Roberto R Anker Stefan D SD Joseph Amer A Lawatscheck Robert R Wilson Daniel D Gebel Martin M Bakris George L GL

Clinical kidney journal 20221030 2

<h4>Background</h4>Mineralocorticoid receptor antagonists (MRAs) reduce systolic blood pressure (SBP) and increase serum potassium concentration ([K<sup>+</sup>]). 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.<h4>Methods</h4>In FIDELITY (a pooled analysis of FIDELIO-DKD and FIGARO-DKD), a subgroup of patients with treatment-resistant hypertension (TRH) ...[more]

PMID: 36864892

Similar Datasets

Project description:ObjectivesThis study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex.DesignFIDELITY post hoc analysis; median follow-up of 3 years.SettingFIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials.ParticipantsAdults with type 2 diabetes and chronic kidney disease receiving optimised renin-angiotensin system inhibitors (N=13 026).InterventionsRandomised 1:1; finerenone or placebo.Primary and secondary outcome measuresCardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes.ResultsMean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65-74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65-74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); Pinteraction=0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); Pinteraction=0.99). Effects on HHF reduction were not modified by age (Pinteraction=0.70) but appeared more pronounced in males (Pinteraction=0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65-74 but not ≥75; no heterogeneity in treatment effect was observed (Pinteraction=0.51). In sex subgroups, finerenone consistently reduced kidney events (Pinteraction=0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups.ConclusionsFinerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups.Trial registration numbersNCT02540993, NCT02545049.

Project description:Rationale & objectiveIn FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes. This analysis explores the efficacy and safety of finerenone in Hispanic patients.Study designPost hoc analysis of the FIDELITY prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD randomized control trials.Setting & participantsPatients with type 2 diabetes and CKD (urinary albumin-to-creatinine ratio [UACR] of ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] of ≥25-≤90 mL/min/1.73 m2, or UACR of ≥300 to ≤5,000 and eGFR of ≥25 mL/min/1.73 m2) on optimized renin-angiotensin system blockade.InterventionFinerenone or placebo.OutcomesCardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure); kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death); change in UACR.ResultsOf 13,026 patients, 2,099 (16.1%) self-identified as Hispanic. Median follow-up was 3.0 years. The cardiovascular composite outcome occurred in 10.0% of Hispanic patients receiving Finerenone and in 12.3% of Hispanic patients receiving placebo (HR, 0.80; 95% CI, 0.62-1.04). This was consistent with non-Hispanic patients (HR, 0.87; 95% CI, 0.79-0.97; Pinteraction= 0.59). The kidney composite outcome occurred in 6.5% and 6.6% of Hispanic patients with finerenone and placebo, respectively (HR, 0.94; 95% CI, 0.67-1.33). The risk reduction was consistent with that observed in non-Hispanic patients (HR, 0.75; 95% CI, 0.64-0.87; Pinteraction= 0.22). Finerenone reduced UACR by 32% at month 4 in both Hispanic and non-Hispanic patients versus placebo (P < 0.001 for both patient groups). The safety profile of finerenone and incidence of hyperkalemia was similar between Hispanic and non-Hispanic patient groups.LimitationsSmall sample size, short follow-up time, and lower treatment adherence in the Hispanic population.ConclusionsOverall, the efficacy and safety of finerenone were similar in Hispanic and non-Hispanic patients with CKD and type 2 diabetes.FundingBayer AG.Trial registrationClinicalTrials.gov identifier: NCT02540993, NCT02545049.Plain-language summaryChronic kidney disease (CKD) in patients with type 2 diabetes occurs more frequently in Hispanic patients than in non-Hispanic patients, with a more rapid progression to kidney failure. Treatment with finerenone reduces the risk of having a kidney or heart event (such as starting dialysis or having a heart attack) in patients with CKD and type 2 diabetes. Because clinical trials that investigate treatments for CKD and type 2 diabetes have not included enough Hispanic patients, the benefits of treatments particularly for Hispanic patients are frequently unknown. This study explores the benefits of finerenone in Hispanic patients. Overall, the study shows that finerenone can provide kidney and heart benefits in Hispanic patients with CKD and type 2 diabetes, as it does in non-Hispanic patients.

Project description:Chronic kidney disease (CKD) is associated with a substantial risk of progression to end-stage renal disease and vascular events. The nonsteroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardiorenal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomized, open, blinded endpoint trial, we assessed the effectiveness of 25 mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age = 74.8 years and s.d. = 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomization until the first occurrence of death, hospitalization for heart disease, stroke, heart failure, transient ischemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across 3 years of follow-up, the primary endpoint occurred in 113 of 677 participants randomized to spironolactone (16.7%) and 111 of 695 participants randomized to usual care (16.0%) with no significant difference between groups (hazard ratio = 1.05, 95% confidence interval: 0.81-1.37). Two-thirds of participants randomized to spironolactone stopped treatment within 6 months, predominantly because they met prespecified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met prespecified stop criteria (n = 239, 35.4%), followed by participants being withdrawn due to treatment side effects (n = 128, 18.9%) and hyperkalemia (n = 54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369 .

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets