Vasopressin receptor antagonists for the treatment of heart failure: a systematic review and meta-analysis of randomized controlled trials (original) (raw)
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Clinical Pharmacology & Therapeutics, 2014
Elevated levels of arginine vasopressin (AVP) are associated with a worse prognosis and the development of hyponatremia in patients with heart failure (HF). This observation led to the development of AVP receptor antagonists for the treatment of HF patients. Although AVP receptor antagonists increase serum sodium, their overall benefits in patients with HF have been at best modest, and recent data raise concerns about their safety in patients with acute HF and low serum sodium.
Journal of Clinical Medicine, 2016
In the congestive heart failure (CHF) setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs) is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.
Hyponatremia and Vasopressin Antagonism in Congestive Heart Failure
Clinical Cardiology, 2007
In a national heart failure registry, hyponatremia (serum sodium <130 mEq/L) was initially reported in 5% of patients and considered a risk factor for increased morbidity and mortality. In a chronic heart failure study, serum sodium level on admission predicted an increased length of stay for cardiovascular causes and increased mortality within 60 days of discharge. Hyponatremia in patients with congestive heart failure (CHF) is associated with a higher mortality rate. Also, by monitoring and increasing serum sodium levels during hospitalization for CHF, patient outcomes may improve. This review describes the pathophysiology of hyponatremia in relation to CHF, including the mechanism of action of vasopressin receptors in the kidney, and assesses the preclinical and clinical trials of vasopressin receptor antagonists-agents recently developed to treat hyponatremia. In hospitalized patients with CHF, hyponatremia plays a major role in poor outcomes. Vasopressin receptor antagonists have been shown to be safe and effective in clinical trials in patients with hyponatremia.
Role of vasopressin antagonists in the management of acute decompensated heart failure
Current heart failure reports, 2005
Vasopressin antagonists are a class of neurohormonal antagonists with applications in both the short-term and long-term management of patients with acute decompensated heart failure (ADHF). The pharmacologic effects of vasopressin antagonists include changes in fluid balance and hemodynamics that may improve symptoms and outcomes in patients hospitalized with ADHF. With chronic therapy, vasopressin antagonists offer the potential to improve outcomes through a variety of mechanisms, including more effective treatment of congestion, preservation or improvement of renal function, or a reduction in the use of concomitant loop diuretic therapy. Several vasopressin antagonists are currently in advanced clinical trials for the treatment of ADHF, chronic stable heart failure, and hyponatremia.
JAMA, 2007
for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators H EART FAILURE (HF) IS A MAjor international public health problem presenting significant medical and economic challenges. In the United States, HF has high prevalence (Ͼ5 million individuals), high incidence (550 000 new cases yearly), increasing hospitalization rates (400 000 in 1979 to Ͼ1 million in 2004), and exorbitant cost (estimated to exceed $33 billion in 2007). 1 A considerable share of the burden of HF is accounted for by the acute HF syndromes (AHFS), defined as conditions with gradual or rapid changes in the signs and symptoms of HF that require urgent therapy. 2 Patients hospitalized with AHFS have poor overall prognosis. 3-8 Congestion characterized by dyspnea, edema, rales, jugular venous dis-See also pp 1319 and 1374.
Journal of Pharmacology and Experimental Therapeutics, 2008
Objective: Arginine vasopressin (AVP) plays an important role in renal hemodynamic alterations, water retention, and cardiac remodeling in congestive heart failure (CHF). The present study evaluated the acute and chronic effects of V 1a and V 2 antagonists on renal function and cardiac hypertrophy in rats with CHF. Methods: The effects of acute administration of SR49059 (0.1mg/kg) and SR 121463B (0.3mg/kg), V 1a and V 2 antagonists, respectively on renal function, and of chronic treatment (3.0mg/kg/day for 7 or 28 days, via osmotic minipumps or P.O), on water excretion and cardiac hypertrophy were studied in rats with aorto-caval fistula and control rats. Results: CHF induction increased plasma AVP (12.8±2.5 vs. 32.2±8.3 pg/ml, P<0.05). Intravenous bolus injection of SR121463B to controls produced dramatic diuretic response (from 5.5±0.8 to 86.3±21.9 µl/min ; p<0.01). In contrast, administration of SR49059 did not affect urine flow. Similarly, administration of SR121463B, but not SR49059, to rats with CHF significantly increased V from 20.8±6.4 to 91.6±26.5 µl/min (p<0.01). The diuretic effects of SR 121463B were associated with significant decline in urinary osmolality and insignificant change of Na+ excretion. In line with its acute effects, chronic administration of SR121463B to CHF rats increased daily urinary volume 2-5 fold throughout the treatment period. Both SR121463B and SR49059 significantly reduced heart weight in CHF rats when administered for 4, but not 1 week. Conclusions: These results suggest that V 2 and V 1a antagonists improve water balance and cardiac hypertrophy in CHF, and might be beneficial for the treatment of water retention and cardiac remodeling in CHF. This article has not been copyedited and formatted. The final version may differ from this version.
JAMA, 2004
OSPITALIZATIONS FOR HEART failure are common in the United States. The most recent data from the National Hospital Discharge Survey indicate 995000 discharges for heart failure in 2001, at a rate of 35.1 per 10000 patients. 1 These patients commonly have a history of progressive volume retention manifested by an increase in body weight, leading to worsening symptoms requiring hospitalization. 2,3 Pharmacological management of systemic congestion in heart failure is often inadequate; in spite of a transient symptomatic improvement, the 6-month post-discharge readmission rates are as high as 50%. 4,5 Although non-potassiumsparing diuretics are the mainstay therapy for congestion, their use is often associated with hypotension, electrolyte abnormalities, worsening renal Author Affiliations, Financial Disclosures, and a List of the ACTIV in CHF Investigators are listed at the end of this article.
AJP: Renal Physiology, 2006
Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single oral dose of tolvaptan, a selective V2-receptor blocker, in the absence of other medications, on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide. We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics, plasma electrolyte concentration, or neurohumoral activation in stable human CHF. Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label, randomized, placebo-controlled crossover study in 14 patients with NYHA II-III CHF. Pa...