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Management of Hypertension in Heart Failure
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Jesse Kane, Clive Goulbourne, Hal A. Skopicki
Newer mineralocorticoid antagonists have enhanced theoretical benefits, given a greater ability to reduce BP and afterload. In HFrEF patients with worsening chronic HF, concomitant type 2 diabetes mellitus, and/or CKD, finerenone was associated with a significant reduction in death from any cause, cardiovascular hospitalizations, and emergency presentation for worsening HF until day 90 when compared with eplerenone in the ARTs-HF (MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure) trial.115 A systemic review also reported that finerenone had fewer treatment-related adverse events, including lower serum potassium levels and higher eGFR vs steroidal MRAs.116
Hypertension in Patients with Advanced Chronic Kidney Disease
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Charalampos Loutradis, Pantelis Sarafidis
Addition of a mineralocorticoid-receptor-antagonist to patients already on ACEI or ARB is suggested as another option for renoprotection, since plasma aldosterone is elevated in CKD and may independently contribute to renal injury (55), whereas use of ACEIs or ARBs does not necessarily result in maintained reductions in plasma aldosterone (56). Addition of spironolactone in proteinuric patients receiving ACEIs or ARBs reduced proteinuria in several pilot studies (57–60). Similarly, eplerenone added to an ACEI further reduced UAE in patients with hypertension and left ventricular hypertrophy (LVH) (61). Increase of serum potassium to more than 5.5 mEq/L, is always a case of concern (62,63) and when such agents are used, serum potassium must be followed closely, and a dose adjustment of the concomitant conventional diuretic therapy should be considered. A detailed study randomized 81 patients with diabetes, hypertension and macroalbuminuria already on lisinopril 80 mg, to losartan 100 mg, spironolactone 25 mg or placebo for 48 weeks (64). Compared to placebo, ACR decreased by 34.0% with spironolactone and by 16.8% with losartan; ambulatory BP, creatinine clearance (CrCl), sodium and protein intake, and glycaemic control did not differ between groups. Serum potassium was higher with either spironolactone or losartan (yet on average >5.2 mEq/L in all groups). A new aldosterone-blocker with the potential for less hyperkalaemia, finerenone, was recently tested in 823 diabetic patients with micro- or macroalbuminuria randomized to finerenone 1.25, 2.5, 5, 7.5, 10, 15 and 20 mg/d or placebo for 90 days (65). ACR significantly decreased by 21%, 24%, 33% and 38% relative to baseline, whereas hyperkalaemia leading to discontinuation was up to 3.2% with finerenone. Based on the above promising findings, the use of finerenone is currently tested in two outcome trials in individuals with diabetic CKD.
Optimization of potassium management in patients with chronic kidney disease and type 2 diabetes on finerenone
Published in Expert Review of Clinical Pharmacology, 2023
Alberto Ortiz, Roberto Alcázar Arroyo, Pedro Pablo Casado Escribano, Beatriz Fernández-Fernández, Francisco Martínez Debén, Juan Diego Mediavilla, Alfredo Michan-Doña, Maria Jose Soler, Jose Luis Gorriz
Finerenone is currently indicated for the treatment of adults with type 2 diabetes and CKD with albuminuria [51]. Finerenone can be taken with or without food and is rapidly (maximum plasma concentrations reached at 0.5–1.25 hours) and almost completely absorbed. The absolute bioavailability of finerenone is nearly 45% due to the first-pass metabolism (gut-wall and liver), with a high protein binding (92%). As a result, it is not expected to be dialyzable. Approximately 90% of finerenone is metabolized by CYP3A4 and the remaining 10% by CYP2C8. Finerenone should not be taken with strong inhibitors or inducers of CYP3A4 and when concomitantly treated with weak or moderate inhibitors, additional monitoring of potassium levels should be performed (Table 1). The elimination half-life is about 2 to 3 hours, being excreted by urine (80%) and feces (20%). Body weight, age, kidney function and liver function do not have a clinically significant impact on the pharmacokinetics of finerenone [51].
Optimal cardiovascular medical therapy: current guidelines and new developments
Published in Baylor University Medical Center Proceedings, 2022
Shirley Cotty Reed, Nikita Dhir, R. Jay Widmer
In the category of renin-angiotensin system (RAS) blockade therapies, finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, demonstrated favorable outcomes in the FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease) trial. The study aimed to determine the safety and efficacy of finerenone in reducing cardiovascular events among patients with type 2 diabetes mellitus and chronic kidney disease on maximal RAS blockade therapy at baseline. Outcomes revealed that new-onset heart failure was significantly reduced and there was an 18% lower risk of cardiovascular death or first heart failure hospitalization in the finerenone group vs placebo.31 Further studies are needed to determine whether finerenone is superior to the mineralocorticoid receptor antagonists spironolactone and eplerenone regarding cardiovascular outcomes and potential risks or side effects. Further studies could also address if use of finerenone in combination with other therapies recommended for patients with type 2 diabetes mellitus and chronic kidney disease can lead to additional cardiovascular benefits.
Efficacy and safety of finerenone for treatment of diabetic kidney disease: current knowledge and future perspective
Published in Expert Opinion on Drug Safety, 2022
Vincenzo Marzolla, Marco Infante, Andrea Armani, Manfredi Rizzo, Massimiliano Caprio
The time span of development between the first and the third generation MRAs is remarkable. Since the introduction of the first MRA in 1960, it has taken half a century to develop a MRA with greater potency and higher selectivity for the MR. Compared to steroidal MRAs, finerenone has a lower IC50 (half maximal inhibitory concentration) for the MR, indicating a more powerful pharmacological antagonism toward the MR [22]. Further, the magnitude of selectivity of finerenone for MR versus other oxo-steroid receptors (androgen receptor and progesterone receptor) is higher compared to steroidal MRAs. Such selectivity suggests that the risk of developing progestogenic and anti-androgenic-related side effects during finerenone therapy is reduced. To date, steroidal MRAs have been designed as a class 1 indication in both American and European guidelines for patients with chronic heart failure [89,90]. MRAs have also been found to reduce cardiovascular mortality and hospitalization for heart failure in selected patients with heart failure and preserved left ventricular ejection fraction [91]. The most common adverse effect of steroidal MRAs is represented by hyperkalemia and renal dysfunction, especially in those patients with concomitant CKD and T2DM [33]. The fear of inducing hyperkalemia has prevented many clinicians from using MRAs for several patients with heart failure. Of note, the incidence of clinically relevant hyperkalemia with finerenone was very low, as reported in FIDELIO-DKD and FIGARO-DKD trials [25,80].