Finerenon je vysoce selektivní, nesteroidní antagonista mineralokortikoidního receptoru (MR) s vyšší vazebnou afinitou než spironolakton nebo eplerenon. Na rozdíl od těchto steroidních inhibitorů MR prokázal finerenon jak kardiovaskulární, tak i renální benefit. Finerenon redukuje albuminurii, která představuje časnější a citlivější marker chronického onemocnění ledvin a zvýšeného KV rizika než samotný pokles eGFR (estimated glomerular filtration rate – odhadnutá hodnota glomerulární filtrace). Také u pacientů se srdečním selháním zvyšuje albuminurie riziko progrese srdečního selhání nebo kardiovaskulárního úmrtí. Finerenon je v současnosti indikován u dospělých pacientů k léčbě chronického onemocnění ledvin s albuminurií, spojeného s diabetem mellitem 2. typu. Tito pacienti by měli být léčeni maximální tolerovanou dávkou inhibitorů systému renin-aniotenzin-aldosteronového systému a gliflozinem. Pokud se jedná o pacienta se srdečním selháním, musí mít ejekční frakci levé komory ≥ 40 %. Před zahájením léčby finerenonem je nutné znát eGFR, kalemii a UACR (urine albumin-creatinine ratio – poměr albuminu a kreatininu v moči); léčbu je možno zahájit při eGFR 25–59 ml/min, kalemii pod 5,0 mmol/l a UACR ≥ 3 mg/mmol (≥ 30 mg/g). Po zahájení léčby je nutno v čtyřtýdenním intervalu kontrolovat hladinu kalemie a eGFR. Pokles UACR je možno pozorovat již po 4 měsících léčby a je dobrým markerem adherence pacientů k léčbě. V článku je dále diskutován dopad na hodnoty krevního tlaku, albuminurii a renální funkce. Jsou probírány i možné nežádoucí účinky. Celý článek ilustrativně doplňují dvě kazuistiky pacientů léčených finerenonem.
Finerenone is a highly selective, non-steroidal mineralocorticoid receptor antagonist with high binding affinity (higher than spironolactone and eplerenone). In contrast to the steroidal mineralocorticoid receptor antagonists, finerenone proved cardiovascular and renal benefit. Finerenone reduces albuminuria, which is a sensitive marker of chronic kidney disease and cardiovascular risk. It is an earlier marker than decreased glomerular filtration rate (GFR). Albuminuria is a marker of increased risk of progression of heart failure and cardiovascular death. Currently, finerenone is indicated to adult patients with type 2 diabetes mellitus with chronic kidney disease with albuminuria. These patients should be treated with maximal tolerated doses of renin angiotensin aldosterone system inhibitors and gliflozins. If a patient had a heart failure, the ejection fraction should be above 40 %. Before starting the therapy with finerenone, it is necessary to know the GFR, potassium level in serum and urine albumin-creatinine ratio (UACR). The therapy can be initiated if GFR is 25-59ml/min, potassium level below 5,0 mmol/L and UACR above 3mg/mmol (≥ 30 mg/g). The potassium serum level and GFR should be controlled within a 4 weeks interval after the initiation of the therapy. Decreased UACR can be observed after 4 months of therapy and it is a very good marker of the patient's adherence to the therapy. The article, beside the possible side effects, discusses the impact of finerenone on blood pressure, albuminuria and renal functions. The whole article is well illustrated by two cases of patients treated with finerenon.
- Keywords
- finerenon,
- MeSH
- Biomarkers MeSH
- Renal Insufficiency, Chronic * drug therapy MeSH
- Diabetes Mellitus, Type 2 MeSH
- Hyperkalemia drug therapy MeSH
- Humans MeSH
- Naphthyridines pharmacology therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Pokroky ve farmakoterapii přinesly nové možnosti léčby srdečního selhání. Léčba srdečního selhání se sníženou ejekční frakcí má čtyři základní pilíře – základní léky. Aktualizace doporučených postupů rozšířila možnosti léčby pro srdeční selhání s mírně sníženou a zachovalou ejekční frakcí levé komory. Kromě inhibitorů sodíkoglukózového ko-transportéru 2 je novou nadějí pro pacienty se srdečním selháním a ejekční frakcí levé komory nad 40 % selektivní nesteroidní antagonista mineralokortikoidních receptorů – finerenon.
Advances in pharmacotherapy have brought new possibilities in the treatment of heart failure. Therapy of heart failure with reduced ejection fraction has four basic pillars - fundamental drugs. Update of heart failure guidelines extended new options in the treatment of heart failure with preserved and mildly reduced ejection fraction. In additon to sodium glucose co-transporter 2 inhibitors, it is a hope for patients with heart failure and ejection fraction over 40 % selective non-steroideal mineralocorticoid receptro antagonist - finerenon.
- Keywords
- finerenon,
- MeSH
- Sodium-Glucose Transporter 2 Inhibitors pharmacokinetics therapeutic use MeSH
- Humans MeSH
- Naphthyridines pharmacology therapeutic use MeSH
- Heart Failure * drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Předložený text pojednává o antagonistech mineraiokortikoidních receptorů, jejich mechanismu účinku, terapeutickém využití v současné medicíně a možných perspektivách budoucího výzkumu. Cílem je poskytnout komplexní pohled na tuto důležitou skupinu léčiv a blíže se zaměřit na jejího nového zástupce finerenon.
The presented text discusses mineralocorticoid receptor antagonists, their mechanism of action, therapeutic use in contemporary medicine and possible perspectives of future research. The aim is to provide a comprehensive view of this important class of drugs and to focus more closely on its new representative, finerenone.
- Keywords
- finerenon,
- MeSH
- Albuminuria diagnosis MeSH
- Mineralocorticoid Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Renal Insufficiency, Chronic * diagnosis drug therapy complications MeSH
- Diabetes Mellitus, Type 2 drug therapy complications MeSH
- Humans MeSH
- Naphthyridines MeSH
- Aged MeSH
- Kidney Function Tests methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
- Keywords
- finerenon,
- MeSH
- Mineralocorticoid Receptor Antagonists MeSH
- Renal Insufficiency, Chronic drug therapy complications MeSH
- Diabetes Mellitus, Type 2 * drug therapy complications MeSH
- Insulin Resistance MeSH
- Humans MeSH
- Naphthyridines therapeutic use MeSH
- Heart Disease Risk Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comment MeSH
- Overall MeSH
BACKGROUND: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed. METHODS: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed. RESULTS: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia. CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.).
- MeSH
- Mineralocorticoid Receptor Antagonists * administration & dosage adverse effects MeSH
- Double-Blind Method MeSH
- Hospitalization statistics & numerical data MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Naphthyridines * administration & dosage adverse effects MeSH
- Follow-Up Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure * drug therapy mortality physiopathology MeSH
- Stroke Volume * drug effects physiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Diabetes mellitus predstavuje najčastejšiu príčinu chronickej choroby obličiek (CKD), ktorá postupne vedie až k terminálnemu zlyhaniu s potrebou náhrady funkcie obličiek. Pacienti s ochorením diabetes mellitus 2. typu (DM2T) sú vo vyššom riziku vzniku kardiovaskulárnych príhod (infarkt myokardu, cievna mozgová príhoda, arytmie a srdcové zlyhanie] a progresie chronickej choroby obličiek. Cieľom je predchádzať týmto komplikáciám zmenou životného štýlu, pravidelným monitorovaním hladiny tlaku krvi a glykémií, ale aj užívaním kardioprotektívnych a nefroprotektívnych liečiv. Finerenón ako nesteroidný selektívny antagonista mineralokortikoidných receptorov, predstavuje spolu s inhibítormi angiotenzín-konvertujúceho enzýmu (ACEi) alebo blokátormi angiotenzín II receptorov (ARB) a inhibítormi sodíkovo-glukózového kotransportéru 2 (SGLT2i) základný pilier liečby u pacientov s DM2T a CKD na zabránenie progresie chronickej choroby obličiek a prevencie kardiovaskulárnych príhod. V tomto článku sa nachádzajú bližšie informácie o mechanizme účinku finerenónu, o výsledkoch štúdií zaoberajúcich sa finerenónom (FIDELIO-DKD a FIGARO-DKD) a o indikačných kritériách, ktoré platia na Slovensku a musia byť splnené pred pridaním finerenónu do liečby. Na záver predstavujeme krátku kazuistiku nášho pacienta s ukážkou efektu liečby finerenónom v praxi.
Diabetes mellitus is the most common cause of chronic kidney disease (CKD), which progressively leads to end-stage renal failure with the need for renal replacement. Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cardiovascular events (myocardial infarction, stroke, arrhythmias and heart failure] and progression to chronic kidney disease. The aim is to prevent these complications by lifestyle changes, regular monitoring of blood pressure and glycemic levels, as well as the use of cardioprotective and nephroprotective drugs. Finerenone, as a non-steroidal selective mineralocorticoid receptor antagonist, represents, together with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), the mainstay of treatment in patients with T2DM and CKD to prevent the progression of chronic kidney disease and prevent cardiovascular events. This article provides more information on the mechanism of action of finerenone, the results of the finerenone trials (FIDELIO-DKD and FIGARO-DKD), and the indication criteria that are valid in Slovakia and must be met before finerenone can be added to the treatment regimen. Finally, we present a short case report of our patient showing the effect of finerenone treatment in practice.
- Keywords
- finerenon,
- MeSH
- Mineralocorticoid Receptor Antagonists therapeutic use MeSH
- Renal Insufficiency, Chronic diagnosis drug therapy complications MeSH
- Diabetes Mellitus, Type 2 diagnosis drug therapy complications MeSH
- Diabetes Mellitus diagnosis drug therapy MeSH
- Diabetic Nephropathies * diagnosis epidemiology drug therapy MeSH
- Clinical Studies as Topic MeSH
- Diabetes Complications drug therapy prevention & control MeSH
- Middle Aged MeSH
- Humans MeSH
- Naphthyridines therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Keywords
- finerenon,
- MeSH
- Renal Insufficiency, Chronic * drug therapy complications blood MeSH
- Diabetes Mellitus, Type 2 drug therapy MeSH
- Sodium-Glucose Transporter 2 Inhibitors therapeutic use MeSH
- Diabetes Complications MeSH
- Humans MeSH
- Naphthyridines * administration & dosage adverse effects therapeutic use MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.
- MeSH
- Mineralocorticoid Receptor Antagonists * therapeutic use MeSH
- Double-Blind Method MeSH
- Ventricular Function, Left physiology drug effects MeSH
- Glomerular Filtration Rate physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Naphthyridines * therapeutic use MeSH
- Natriuretic Peptide, Brain blood MeSH
- Aged MeSH
- Heart Failure * physiopathology drug therapy MeSH
- Stroke Volume * physiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
