cardiovascular-agents and Hyponatremia

The role of arginine vasopressin in heart failure and the use of vasopressin receptor antagonists in the treatment of heart failure are reviewed.. Arginine vasopressin (AVP) functions in the regulation of plasma osmolarity and blood pressure. In heart failure, AVP worsens heart failure by causing vasoconstriction of arteries and veins, potentially contributing to remodeling of the left ventricle and causing fluid retention and worsening of hyponatremia. Two V(2)-receptor antagonists, tolvaptan and lixivaptan, and one combined V(1a)- and V(2)-receptor antagonist, conivaptan, have shown promise for use in patients with heart failure. All three agents have been shown to increase free water excretion and increase serum sodium levels while maintaining serum potassium levels. They have not been shown to decrease renal function or the glomerular filtration rate and are well tolerated, with thirst being the major adverse effect during clinical trials. Because of their effects on sodium, vasopressin antagonists need to be carefully monitored to ensure that serum sodium levels do not increase too quickly and put the patient at risk for overcorrection or osmotic demyelination syndrome. In addition, patients need to be monitored for signs of dehydration secondary to increased urine excretion. To date, studies have not consistently shown improvements in patient symptoms or weight reduction. However, early data suggest that at least one agent, tolvaptan, does not alter mortality.. Based on data from available clinical trials, vasopressin antagonists may offer a new treatment option for patients with congestive heart failure. However, these agents do not currently appear to delay the progression of heart failure or decrease mortality.

Topics: Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Azepines; Benzamides; Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure; Humans; Hyponatremia; Pyrroles; Receptors, Vasopressin; Tolvaptan

Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.. To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.. Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021.. Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.. The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2).. Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively.. Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.. ClinicalTrials.gov Identifier: NCT03640949.

Topics: Aged; Cardiovascular Agents; Confidence Intervals; Denmark; Double-Blind Method; Epinephrine; Female; Glucocorticoids; Heart Arrest; Humans; Hyperglycemia; Hyponatremia; Male; Methylprednisolone; Neurologic Examination; Placebos; Return of Spontaneous Circulation; Treatment Outcome; Uncertainty; Vasoconstrictor Agents; Vasopressins

We conducted a prospective evaluation of drug-induced severe hyponatremia  (adverse drug reaction (ADR)) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital over a period of 10 years. Cases of serum sodium (Na(s)) < 116 mM were recorded from July 2007 to June 2017 (first period). Also cases of Na(s) 116-122 mM were recorded from July 2012 to June 2017 (second period). Drugs were the primary cause of severe hyponatremia. The incidence rate of Na(s) < 116 mM by drugs was increased threefold over the decade. Compared with other causes of hyponatremia, patients with adverse drug reaction-serum sodium (ADR-Na(s)) in the first period were older (79 years (interquartile range (IQR) 68.6-89 vs. 65 years (IQR 48-81); P < 0.001) and were more often women (70.8% vs. 48.9% men, P < 0.001); in the second period were also older (79 years (IQR 65.3-89) vs. 63 years (IQR 46-80.6); P < 0.001) and were more often women (70% vs. 53%, P = 0.002), and ADR-Na(s) occurred more often in summer. The most frequent therapeutic groups of culprit drugs were the cardiovascular system and nervous system. The 65.3% in the first period and 71.2% in the second period of the ADR-Na(s) cases responded to hydration and had been diagnosed with hypovolemic hyponatremia.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Bacterial Agents; Anticonvulsants; Antineoplastic Agents; Bolivia; Cardiovascular Agents; Child; Child, Preschool; Cholinergic Antagonists; Female; Gastrointestinal Agents; Humans; Hypoglycemic Agents; Hyponatremia; Infant; Infant, Newborn; Male; Middle Aged; Pharmacovigilance; Prospective Studies; Psychotropic Drugs; Seasons; Severity of Illness Index; Young Adult

INTRODUCTION The aim of this study is to determine the prevalence of hyponatremia, its association with long-term medication use and underlying chronic conditions, the rate of hospitalisation and death within 3 months from its discovery and its management in community-dwelling older people. METHODS One year of data for ~5635 patients aged >65 years was extracted from the databases of 19 general practitioners (GPs); 2569 (45.6%) were checked for hyponatremia. RESULTS Hyponatremia occurred in 205 (8.0%) of 2569 checked individuals: 78.5% (161/205) had hypertension, 31.2% (64/205) diabetes, 23.9% (49/205) chronic renal failure; 38.0% (78/205) received diuretics, 36.6% (75/205) renin-angiotensin system antagonists (ACE-I/ARB) and 9.8% (20/205) serotonin reuptake inhibitors. Drug consumption was higher in hyponatremic patients, although only diuretics, ACE-I/ARB, anti-arrhythmics and opioids were significantly associated with hyponatremia. The likelihood of hyponatremia trebled when four drugs were taken, and it was seven-fold higher with the use of six drugs. Hyponatremia was associated with a higher prevalence of chronic illnesses and higher rate of hospitalisation (13.7% vs 7.7%, P = 0.005) and death (3.9% vs 1.8%, P < 0.035). The use of at least one long-term medication was associated with hospitalisation or death in hyponatremic patients (10% vs 6.3%, P = 0.010). Less than 20% of hyponatremic patients had their sodium level checked again after 1 month. DISCUSSION Hyponatremia is not uncommon among community-living older patients, especially in patients taking medications potentially causing hyponatremia. Hyponatremic patients are likely to encounter more serious events, including hospitalisation and death. Targeted training of GPs is desirable to improve their practice.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Diuretics; Female; General Practice; Hospitalization; Humans; Hyponatremia; Italy; Male; Polypharmacy; Prevalence

Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients.. The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients.. The mean admission sodium level was 138 ± 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na(+) < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and β-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients.. In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts.

Topics: Aged; Aged, 80 and over; Asia; Asian People; Biomarkers; Cardiovascular Agents; Disease-Free Survival; Female; Guideline Adherence; Healthcare Disparities; Heart Failure; Hospitalization; Humans; Hyponatremia; Male; Middle Aged; Practice Guidelines as Topic; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Sodium; Stroke Volume; Time Factors; Treatment Outcome

Acute heart failure syndromes are a common cause of emergency department visits and hospitalization in North America and Europe. Although in-hospital mortality is relatively low, the postdischarge mortality and rehospitalization rates can be as high as 10-15 and 30%, respectively, within 60-90 days following discharge. It appears that the main reason for admission and readmission for heart failure is related to congestion manifested by dyspnea, jugular venous distension and edema. Often, congestion is associated with dilutional hyponatremia that is difficult to treat. Hyponatremia is an important predictor of increased mortality and the available therapies to treat congestion and/or hyponatremia are often ineffective and/or unsafe. Accordingly, there is an unmet need to develop a new agent that effectively relieves congestion due to high filling pressure without worsening renal function and improving or normalizing serum sodium in hyponatremic patients. This paper provides an overview of a new compound, tolvaptan, an oral selective V(2)-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. The biochemical and pharmacological properties are discussed in conjunction with its clinical efficacy and safety, exploring the potential role of tolvaptan in the management of acute heart failure syndromes presenting with or without hyponatremia.

Topics: Acute Disease; Aged; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiovascular Agents; Europe; Female; Heart Failure; Hospitalization; Humans; Hyponatremia; Male; Middle Aged; North America; Randomized Controlled Trials as Topic; Tolvaptan