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

Author:

Agarwal Rajiv1ORCID,Pitt Bertram2,Palmer Biff F3,Kovesdy Csaba P45ORCID,Burgess Ellen6,Filippatos Gerasimos7,Małyszko Jolanta8,Ruilope Luis M91011,Rossignol Patrick12ORCID,Rossing Peter1314ORCID,Pecoits-Filho Roberto1516,Anker Stefan D17,Joseph Amer18,Lawatscheck Robert18,Wilson Daniel19,Gebel Martin20ORCID,Bakris George L21

Affiliation:

1. Richard L. Roudebush VA Medical Center and Indiana University , Indianapolis, IN , USA

2. Department of Medicine, University of Michigan School of Medicine , Ann Arbor, MI , USA

3. Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX , USA

4. Division of Nephrology, Department of Medicine, University of Tennessee, Health Science Center Memphis , TN , USA

5. Nephrology Section, Memphis VA Medical Center , Memphis, TN , USA

6. Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary, AB , Canada

7. National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Attikon University Hospital , Athens , Greece

8. Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw , Warsaw , Poland

9. Cardiorenal Translational Laboratory and Hypertension Unit, Institute of Research imas12 , Madrid , Spain

10. CIBER-CV, Hospital Universitario 12 de Octubre , Madrid , Spain

11. Faculty of Sport Sciences, European University of Madrid , Madrid , Spain

12. Université de Lorraine, Inserm, Centre d’Investigations Cliniques – Plurithématique 14-33, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy , France

13. Steno Diabetes Center Copenhagen , Herlev , Denmark

14. Department of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark

15. Arbor Research Collaborative for Health , Ann Arbor, MI , USA

16. School of Medicine, Pontificia Universidade Católica do Paraná , Curitiba , Brazil

17. Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies , German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin , Germany

18. Cardiology and Nephrology Clinical Development , Bayer AG, Berlin , Germany

19. US Medical Affairs, Bayer US LLC Pharmaceuticals , Whippany, NJ , USA

20. Research and Development, Integrated Analysis Statistics , Bayer AG, Wuppertal , Germany

21. Department of Medicine, University of Chicago Medicine , Chicago, IL , USA

Abstract

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)

Funder

Bayer AG

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

Reference28 articles.

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3. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial;Williams;Lancet,2015

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