Vasopressin V&lt;sub&gt;2&lt;/sub&gt; Receptor Antagonist Tolvaptan Is Effective in Heart Failure Patients With Reduced Left Ventricular Systolic Function and Low Blood Pressure

Suzuki, Satoshi; Yoshihisa, Akiomi; Yamaki, Takashi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Abe, Yukihiko; Saito, Tomiyoshi; Ohwada, Takayuki; Suzuki, Hitoshi; Saitoh, Shu‐ichi; Takeishi, Yasuchika

doi:10.1536/ihj.14-248

Cited by 17 publications

(19 citation statements)

References 22 publications

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“…15) Therefore, a therapeutic strategy to improve prognosis in patients with HFpEF is an importent concern. While TLV has been previously investigated in patients with HFpEF, with Suzuki, et al showing the acute effects of TLV compared with carperitide in patients with HFpEF, 28) there are currently no studies that discussed the long-term efficacy of TLV in patients with HFpEF. Efficacy of TLV in patients with HFrEF: The EVEREST trial failed to show an advantage of add-on TLV therapy in the long-term survival of patients with HFrEF.…”

Section: Discussionmentioning

confidence: 99%

Tolvaptan Improves the Long-Term Prognosis in Patients With Congestive Heart Failure With Preserved Ejection Fraction as Well as in Those With Reduced Ejection Fraction

Imamura

Kinugawa

2016

Int. Heart J.

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SummaryTolvaptan (TLV), an arginine vasopressin type 2 antagonist, has been shown to play a role in ameliorating symptomatic congestion and normalizing diluted hyponatremia in patients with congestive heart failure (HF). However, most evidence was derived from patients with HF with reduced ejection fraction (HFrEF), and the clinical efficacy of TLV in patients with HF with preserved ejection fraction (HFpEF) remains uncertain. In this study, we retrospectively enrolled 60 in-hospital patients with stage D HF, who had received TLV to treat symptomatic congestion at our institute between 2011 and 2013. As a control group, we also enrolled 60 background-matched HF patients who did not receive TLV therapy. Patients with HFpEF (n = 29), whose left ventricular ejection fraction was > 45%, had higher age and a lower urine aquaporin-2 level relative to the plasma arginine vasopressin concentration compared with those with HFrEF (n = 91). TLV therapy significantly reduced the 2-year readmission rates in both the HFrEF and HFpEF populations (P < 0.05 for both), indicating that TLV therapy may improve the long-term prognosis not only in patients with HFrEF but also in those with HFpEF. (Int Heart J 2016; 57: 600-606)

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Section: Discussionmentioning

confidence: 99%

Tolvaptan Improves the Long-Term Prognosis in Patients With Congestive Heart Failure With Preserved Ejection Fraction as Well as in Those With Reduced Ejection Fraction

Imamura

Kinugawa

2016

Int. Heart J.

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“…6) Tolvaptan is a vasopressin type 2 receptor antagonist that is effective in patients with HF. [7][8][9][10][11][12][13][14] Tolvaptan became available in Japan for the treatment of HF in 2010. When sufficient diuresis is not achieved with diuretics such as loop diuretics, tolvaptan is recommended.…”

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confidence: 99%

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure

et al. 2017

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SummaryWe examined whether tolvaptan combined with an angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACE-I) is more effective than tolvaptan alone in the treatment of patients with heart failure (HF). Sixty-five hospitalized patients with acute decompensated HF were included in this study. They were divided into 2 groups; an ARB/ACE-I group (n = 44, who received ARB or ACE-I before the use of tolvaptan) and a non-ARB/ACE-I group (n = 21). There were no significant differences in patient characteristics including medications at baseline between the non-ARB/ACE-I and ARB/ACE-I groups with the exception of the percentages of hypertension and ischemic heart disease. Urinary volume (UV) at baseline in the ARB/ACE-I group was slightly higher than that in the non-ARB/ACE-I group. The increase in UV after the use of tolvaptan in the non-ARB/ACE-I group was significantly higher than that in the ARB/ACE-I group. The cardiothoracic ratio and the reduction in body weight were similar between the groups after tolvaptan use. Finally, in a logistic regression analysis, a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I, but not with age, gender, body mass index, loop diuretic, or human arterial natriuretic peptide. In conclusion, tolvaptan alone might induce an increase in UV in decompensated HF patients without ARB/ ACE-I, although the treatment of HF with ARB/ACE-I is the first choice strategy. (Int Heart J 2017; 58: 385-392)

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“…1) Progression of HF is characterized by sustained deterioration in symptoms, cardiac function, and peripheral and pulmonary vascular resistance. 2,3) Neurohormonal activation, an important factor of left ventricular (LV) remodeling, is likely to be a primary determinant for the progression. The roles of activation of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) in HF are well documented and inhibiting them with angiotensin-converting enzyme inhibitors (ACEI) and β blockers could effectively reverse the process of LV remodeling, relieve patient symptoms, and prolong life.…”

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confidence: 99%

“…In some animal models of chronic HF, ERA has been shown to correct hemodynamic abnormalities, decrease cardi-Vol 58 No 3 ENDOTHELIN RECEPTOR ANTAGONISTS AND HEART FAILURE ac fibrosis, and improve survival. 12) However, a meta-analysis of experimental HF indicated that EARs may not improve the mortality of HF.…”

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confidence: 99%

Clinical and Hemodynamic Effects of Endothelin Receptor Antagonists in Patients With Heart Failure

et al. 2017

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SummaryThe clinical benefit of endothelin receptor antagonists (ERA) for the management of heart failure (HF) remains controversial. To examine this question, we performed a meta-analysis of randomized controlled trials (RCTs) to investigate the clinical and hemodynamic effects of ERA in HF patients.We searched the PubMed, Medline, Embase, and Cochrane Library from inception to March 20, 2016 to identify the pertinent studies. Risk ratio (RR) and weighted mean difference (WMD) were calculated using a fixed or random effect model.A total of 15 RCTs with 3,624 HF patients were included. Compared with control groups, ERA might not improve the mortality (RR 1.12, 95%CI 0.81 to 1.54, P = 0.51) or incidence of worsening HF or cardiovascular events (WHF/ CVE) (RR 1.06, 95%CI 0.94 to 1.19, P = 0.35) in HF patients. Subgroup analysis also suggested that neither nonselective nor selective ERAs had an impact on mortality and WHF/CVE. However, the hemodynamic variables of HF patients, including cardiac index (WMD 0.32, 95%CI 0.22 to 0.43, P < 0.01), pulmonary capillary wedge pressure (WMD -3.10, 95%CI -3.99 to -2.20, P < 0.01), mean pulmonary arterial pressure (WMD -4.42, 95%CI -5.50 to -3.33, P < 0.01), systemic vascular resistance (WMD -276.35, 95%CI -399.62 to -153.09, P < 0.01), and pulmonary vascular resistance (WMD -69.42, 95%CI -105.33 to -33.52, P < 0.01) were significantly improved by ERA.In conclusion, this meta-analysis suggests that ERA therapy could effectively improve cardiac output and pulmonary and systemic hemodynamics, but with less benefit to the clinical outcomes of HF patients. (Int Heart J 2017; 58: 400-408) Key words: Endothelin system, Systematic review H eart failure (HF) is a major public health problem, with a prevalence of more than 23 million worldwide. 1) Progression of HF is characterized by sustained deterioration in symptoms, cardiac function, and peripheral and pulmonary vascular resistance.2,3) Neurohormonal activation, an important factor of left ventricular (LV) remodeling, is likely to be a primary determinant for the progression. The roles of activation of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) in HF are well documented and inhibiting them with angiotensin-converting enzyme inhibitors (ACEI) and β blockers could effectively reverse the process of LV remodeling, relieve patient symptoms, and prolong life. [4][5][6] Furthermore, it has been demonstrated that local activation of the endothelin (ET) system might also be linked with HF progression. 7)ET-1 is thought to mediate potent vasoconstriction, proliferation of vascular smooth muscle, and myocardial hypertrophy through ET A receptors. 8) In contrast, activation of endothelial ET B receptors is primarily involved in vasodilation, antithrombotic, and antiproliferative effects. Moreover, ET-1 also has a potential to enhance the activity of RAS and SNS pathways and induce the production of other neurohormonal factors.9) Plasma levels of ET-1 and big ET-1 are elevated and can significantly predict mortalit...

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Vasopressin V<sub>2</sub> Receptor Antagonist Tolvaptan Is Effective in Heart Failure Patients With Reduced Left Ventricular Systolic Function and Low Blood Pressure

Cited by 17 publications

References 22 publications

Tolvaptan Improves the Long-Term Prognosis in Patients With Congestive Heart Failure With Preserved Ejection Fraction as Well as in Those With Reduced Ejection Fraction

Tolvaptan Improves the Long-Term Prognosis in Patients With Congestive Heart Failure With Preserved Ejection Fraction as Well as in Those With Reduced Ejection Fraction

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure

Clinical and Hemodynamic Effects of Endothelin Receptor Antagonists in Patients With Heart Failure

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