BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA. OBJECTIVES: This study sought to evaluate the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia. METHODS: REALIZE-K (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA-induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia started SZC. Participants with normokalemia (potassium: 3.5-5.0 mEq/L) on SZC and spironolactone ≥25 mg/day were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]). The 5 secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits). RESULTS: Overall, 203 participants were randomized (SZC: 102; placebo: 101). Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001). SZC (vs placebo) improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001); receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001); time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001); and time to decrease/discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). There was no between-group difference in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 6 months (-1.01 points; 95% CI: -6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034). CONCLUSIONS: In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone; NCT04676646).

• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• hyperkalemie * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• silikáty * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• spironolakton * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• srdeční selhání * farmakoterapie   MeSH
• tepový objem účinky léků   fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   škodlivé účinky   MeSH
• cévní mozková příhoda mortalita   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu * mortalita   farmakoterapie   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• spironolakton * terapeutické užití   škodlivé účinky   MeSH
• srdeční selhání * farmakoterapie   mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Pseudohypoaldosteronism type 2 (PHA2) is a rare inherited condition of altered tubular salt handling. It is characterized by the specific constellation of hyperkalaemic hyporeninemic hypertension, hyperchloremic metabolic acidosis and hypercalciuria. Molecular genetic testing confirms the diagnosis in the majority of cases. Thiazides constitute effective treatment. Due to its rarity, the diagnosis is often delayed. We here present two children with PHA2, who were initially treated with fludrocortisone and bicarbonate complicated mainly by exacerbation of their hypertension. Discontinuation of their previous therapy and commencement of thiazide diuretics led to normalisation of their blood pressure and electrolyte and acid-base status.

• MeSH
• acidóza * diagnóza   etiologie   MeSH
• dítě MeSH
• fludrokortison terapeutické užití   MeSH
• hyperkalemie diagnóza   etiologie   genetika   krev   MeSH
• hypertenze * diagnóza   etiologie   farmakoterapie   genetika   MeSH
• inhibitory symportérů pro chlorid sodný terapeutické užití   MeSH
• krevní tlak MeSH
• lidé MeSH
• pseudohypoaldosteronismus * genetika   diagnóza   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

• MeSH
• depreskripce * MeSH
• diuretika * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• hypertenze farmakoterapie   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

Hyponatremia is a crucial complication of therapy with thiazide diuretics. This study compares the epidemiological and biochemical profiles and hospital course of patients using hydrochlorothiazide (HCTZ), indapamide (INDA), and chlorthalidone (CTD) admitted with thiazide-associated hyponatremia (TAH). Data were obtained retrospectively from the hospital's digital registries. The epidemiological and biochemical parameters between the HCTZ, INDA, and CTD groups were compared. The correlation between dose and biochemical parameters in each group was performed. The thiazide groups without diuretic co-medication were compared (HCTZ vs. INDA), and the correlation between dose and biochemical parameters in each group was examined. A comparison of the HCTZ (n = 135), INDA (n = 125), and CTD (n = 27) groups identified differences in serum potassium (s-K; p = 0.03). The hyponatremia correction rate was slower in the CTD group at 96 h after admission (p < 0.001). After the exclusion of diuretic co-medication, the HCTZ group (n = 64/135) showed a higher prevalence of ARBs, s-K (both p < 0.001), and a lower median (IQR) equipotent dose (12.5 (o) mg vs. 2.5 (1.2) mg), prevalence of ACE-I (p < 0.001), and eGFR (p = 0.03), when compared to the INDA group (n = 109/125). In conclusion, except for s-K, we observed no significant difference in biochemical and epidemiological profiles between HCTZ, INDA, and CTD. After excluding the influence of other diuretics, we observed higher s-K in the HCTZ group compared to the INDA group, potentially explained by the lower equipotent dose of HCTZ. The CTD group showed a statistically significant trend of slower hyponatremia correction.

• MeSH
• antihypertenziva škodlivé účinky   MeSH
• chlorthalidon * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• diuretika škodlivé účinky   MeSH
• draslík krev   MeSH
• hydrochlorthiazid * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• hypertenze * farmakoterapie   MeSH
• hyponatremie * chemicky indukované   epidemiologie   krev   MeSH
• indapamid * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory symportérů pro chlorid sodný škodlivé účinky   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 farmakologie   MeSH
• antagonisté mineralokortikoidních receptorů farmakologie   terapeutické užití   MeSH
• diabetické nefropatie * farmakoterapie   MeSH
• glifloziny farmakologie   terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy 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.

• Klíčová slova
• finerenon,
• MeSH
• antagonisté mineralokortikoidních receptorů * farmakologie   terapeutické užití   MeSH
• hodnocení léčiv MeSH
• lidé MeSH
• naftyridiny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• FINERENON,
• MeSH
• albuminurie etiologie   moč   MeSH
• antagonisté mineralokortikoidních receptorů * farmakologie   klasifikace   terapeutické užití   MeSH
• chronická renální insuficience * diagnóza   farmakoterapie   MeSH
• diabetes mellitus 2. typu diagnóza   komplikace   MeSH
• hypertenze farmakoterapie   MeSH
• kazuistiky jako téma MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• přehledy MeSH

Psoriasis is a chronic systemic autoimmune disease associated with an elevated risk of developing cardiovascular disease. In patients with psoriasis, arterial hypertension treatment requires careful selection of antihypertensive drugs, as some drugs may worsen the skin manifestations of psoriasis. In this review, we summarize the available evidence regarding the risks and benefits of each group of antihypertensive drugs. We also suggest a scheme for optimizing antihypertensive treatment in patients with psoriasis, with emphasis on achieving effective control of blood pressure and cardiovascular disease, while minimizing the worsening of cutaneous manifestations. Angiotensin receptor blockers appear to be the most appropriate treatment for hypertensive patients with psoriasis, with the potential addition of calcium channel blockers if blood pressure is not adequately controlled. Alternatives are angiotensin-converting enzyme inhibitors and/or mineralocorticoid receptor antagonists. Diuretics and beta blockers are associated with greater risk of worsening of psoriatic lesions.

• MeSH
• antagonisté mineralokortikoidních receptorů terapeutické užití   MeSH
• antihypertenziva * terapeutické užití   MeSH
• beta blokátory terapeutické užití   škodlivé účinky   MeSH
• blokátory kalciových kanálů terapeutické užití   MeSH
• hypertenze * farmakoterapie   komplikace   MeSH
• inhibitory ACE terapeutické užití   MeSH
• lidé MeSH
• psoriáza * farmakoterapie   komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• blokátory kalciových kanálů farmakologie   terapeutické užití   MeSH
• dietoterapie metody   MeSH
• diuretika farmakologie   terapeutické užití   MeSH
• hypertenze * diagnóza   dietoterapie   farmakoterapie   MeSH
• inhibitory ACE farmakologie   terapeutické užití   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH