Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Journal of Cardiovascular Medicine
(Impact Factor: 1.51).
07/2012; 13(7):415-22. DOI: 10.2459/JCM.0b013e328355a740
Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population.
In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (> 20 mg/dl) and low SBP (<105 mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo.
Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 ± 2.00 vs. 0.76 ± 1.75 kg, P < 0.0001 at day 1 and 3.23 ± 3.36 vs. 2.10 ± 3.47 kg, P < 0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41 ± 3.67 vs. 1.32 ± 3.93 mEq/l, P < 0.0001) and persisted through day 7 or discharge (4.79 ± 4.89 vs. 1.25 ± 5.00 mEq/l, P < 0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105 mmHg and BUN less than 20 mg/dl.
In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function.
Available from: Yasuyuki Shiraishi
- "Matsue et al.  also showed tolvaptan treatment to be associated with the lower incidence of worsening renal dysfunction in Japanese patients with acute HF at high risk for worsening renal dysfunction. As in a previous study , the current case of HF and renal dysfunction was refractory to the intravenous administration of furosemide; however, oral tolvaptan with a small dose of dopamine was strikingly effective in improving both worsening HF and renal dysfunction and reducing the daily dose of furosemide. In addition to tolvaptan, a small dose of dopamine was used to increase renal artery flow. "
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ABSTRACT: The use of loop diuretics has been shown to deteriorate renal dysfunction and is associated with a poor prognosis in patients with heart failure (HF). Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to be effective in treating HF due to its potent effects of water diuresis and is expected to improve fluid retention without adversely affecting renal function. The present case is a 77-year-old man with pulmonary hypertension associated with chronic pulmonary artery thrombosis and old pulmonary tuberculosis who developed worsening right-sided HF with marked fluid retention and renal dysfunction. In this case, tolvaptan was effective in improving HF without deteriorating the patient's renal dysfunction.
<Learning objective: Tolvaptan is effective in treating patients with right-sided heart failure associated with marked fluid retention and renal dysfunction who are refractory to loop diuretics and can improve and control heart failure symptoms without worsening renal dysfunction.
- "In our study, the use of tolvaptan resulted in a mean reduction from baseline in the daily use of furosemide at 7th day of therapy. However, it was statistically insignificant, which was in contrast to the previous studies on tolvaptan. Though there was a reduction in diuretics use, we found rising of blood urea at 7th day after therapy with tolvaptan with decrease serum creatinine, which was suggestive of pre renal cause with intracellular dehydration due to excess free fluid dieresis with tolvaptan treatment. "
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ABSTRACT: In acute decompensated heart failure (ADHF), diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. Vasopressin mediates fluid retention in heart failure. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. Hyponatremia (serum sodium concentration, <135 mEq/L) is a predictor of death among patients with heart failure.
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Hyponatremia is the most common electrolyte disorder encountered in clinical practice and represents a clinical, social, and economic burden. Conventional treatments of hyponatremia present some pitfalls, such as suboptimal efficacy, risk of overly rapid correction, and adverse effects. Vasopressin receptor antagonists, known as vaptans, represent a new and interesting class of drugs for the treatment of the euvolemic and hypervolemic forms of hyponatremia.
This review is based on a PubMed search with the following terms: "vaptans," "vasopressin receptor antagonists," "tolvaptan," "conivaptan," "vasopressin receptor antagonists and SIADH," "vasopressin receptor antagonists and congestive heart failure," "vasopressin receptor antagonists and cirrhosis," and "vasopressin receptor antagonists and polycystic kidney disease."
Overall, the studies reported in this review indicate that vaptans effectively correct hyponatremia in euvolemic and hypervolemic patients. In the latter group, vaptans generally had favorable effects on fluid balance also. To date two vaptans, ie, conivaptan and tolvaptan, have been marketed in the United States for the treatment of euvolemic and hypervolemic hyponatremia, whereas tolvaptan has been marketed in Europe with the limitation of euvolemic hyponatremia. Although these drugs have a good safety profile, caution should be used, and treatment should be initiated in a hospital setting in order to closely monitor patients and avoid overly rapid correction or overcorrection.
Vaptans can be considered a new effective tool for the treatment of euvolemic and hypervolemic hyponatremia. Nevertheless, more comparative research of vaptans vs other therapies on clinical grounds is needed to more accurately assess the value of these drugs in the treatment of hyponatremia.
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