natriuretic-peptide--brain and Hyperkalemia

The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5-10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Topics: Eplerenone; Heart Failure; Hospitalization; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Peptide, Brain; Network Meta-Analysis; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency; Spironolactone; Treatment Outcome

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was evaluated in Japanese patients with heart failure (HF) with reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. ARTS-HF Japan was a randomized, double-blind, phase 2b study. Patients (n=72) received oral, once-daily (o.d.) finerenone (2.5, 5, 7.5, 10 or 15 mg, up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30) or eplerenone (25 mg every other day, increased to 25 mg o.d. on day 30, and 50 mg on day 60) for 90 days. The primary endpoint was the proportion of individuals with a decrease of >30% in plasma NT-proBNP at day 90. Safety endpoints included the incidence of hyperkalemia. Decreases in NT-proBNP occurred in 23.1% of patients in the eplerenone group and 15.4%, 23.1%, 45.5%, 27.3% and 45.5% in the 2.5→5 mg, 5→10 mg, 7.5→15 mg, 10→20 mg and 15→20 mg finerenone groups, respectively (all P=NS). Mean changes in serum potassium levels were similar between groups.. Because of the small sample size, limited conclusions can be drawn. Considering the results of ARTS-HF and that finerenone was well tolerated in Japanese patients in ARTS-HF Japan, the safety and efficacy of finerenone should be further explored in a large outcomes trial including Japanese patients. (Circ J 2016; 80: 1113-1122).

Topics: Adult; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Hyperkalemia; Japan; Naphthyridines; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

Although therapy with mineralocorticoid receptor antagonists (MRAs) is recommended for patients with chronic heart failure (HF) with reduced ejection fraction and in post-infarction HF, it has not been studied well in acute HF (AHF) despite being commonly used in this setting. At high doses, MRA therapy in AHF may relieve congestion through its natriuretic properties and mitigate the effects of adverse neurohormonal activation associated with intravenous loop diuretics. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) trial is a randomized, double-blind, placebo-controlled study of the safety and efficacy of 100 mg/day spironolactone versus placebo (or continued low-dose spironolactone use in participants who are already receiving spironolactone at baseline) in 360 patients hospitalized for AHF. Patients are randomized within 24 h of receiving the first dose of intravenous diuretics. The primary objective is to determine if high-dose spironolactone, compared with standard care, will lead to greater reductions in N-terminal pro-B-type natriuretic peptide levels from randomization to 96 h. The secondary endpoints include changes in the clinical congestion score, dyspnea relief, urine output, weight change, loop diuretic dose, and in-hospital worsening HF. Index hospital length of stay and 30-day clinical outcomes will be assessed. Safety endpoints include risk of hyperkalemia and renal function. Differences among patients with reduced versus preserved ejection fraction will be determined. (Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure [ATHENA-HF]; NCT02235077).

Topics: Acute Disease; Cause of Death; Disease Progression; Double-Blind Method; Dyspnea; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Mortality; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone; Treatment Outcome

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.

Topics: Aged; Biomarkers; Diuretics; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Potassium; Predictive Value of Tests; Prevalence; Prognosis; Prospective Studies; Risk Factors; Spironolactone; Survival Rate; Treatment Outcome

Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy.. To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy.. We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient.. A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p < 0.001) and multivariate analysis (HR = 5.24; 95% CI 1.87-14.72, p = 0.002) after correction for age, ischemic cardiomyopathy, diabetes, systolic arterial pressure, New York Heart Association class 3, left ventricular ejection fraction, presence of hyponatremia, glomerular filtration rate calculated by the EPI formula, and presence of N-terminal pro-B-type natriuretic peptide >1,000 pg/mL.. The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperkalemia; Hyponatremia; Incidence; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Renin-Angiotensin System; Retrospective Studies; Safety-Based Drug Withdrawals; Stroke Volume; Ventricular Dysfunction, Left

Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting.. We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c) (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of diuretics (P=0.0232).. The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Child; Disease Progression; Diuretics; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperkalemia; Male; Middle Aged; Natriuretic Peptide, Brain; Potassium; Regression Analysis; Renal Insufficiency; Renin-Angiotensin System; Severity of Illness Index; Spironolactone; Young Adult

Acute hyponatremia, following neurosurgery, results from inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block all stimulators of zona glomerulosa steroidogenesis, resulting in mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and high natriuresis occurred on day 8, with low renin and aldosterone and elevated BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old boy presented CSW at day 6 after partial resection of optic glioma. Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone supplementation should be considered in CSW, as excessive natriuresis is controlled, and electrolytes are easily restored, avoiding life-threatening complications of this complex disorder.

Topics: Atrial Natriuretic Factor; Cerebrum; Child; Child, Preschool; Craniopharyngioma; Electrolytes; Female; Fludrocortisone; Humans; Hyperkalemia; Hyponatremia; Hypophysectomy; Male; Mineralocorticoids; Natriuretic Peptide, Brain; Pituitary Neoplasms; Postoperative Complications; Postoperative Period; Sodium Chloride

Topics: Acute Kidney Injury; Aged; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medicine; Fatal Outcome; Female; Heart Failure; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Natriuretic Peptide, Brain