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Association between the Serum Sodium Levels and the Response to Tolvaptan in Liver Cirrhosis Patients with Ascites and Hyponatremia.
Hayashi, M, Abe, K, Fujita, M, Okai, K, Takahashi, A, Ohira, H
Internal medicine (Tokyo, Japan). 2018;(17):2451-2458
Abstract
Objective Hyponatremia is closely associated with the pathophysiology of cirrhosis. However, the association between the serum sodium level and the response to tolvaptan is unclear. This study evaluated the factors related to the tolvaptan response and the prognosis in cirrhosis patients with ascites and hyponatremia. Methods We retrospectively reviewed the clinical records of cirrhosis patients hospitalized for treatment with tolvaptan. The associations of patient baseline characteristics with the tolvaptan response after one week and of the characteristics after one-month tolvaptan treatment with the prognosis were analyzed. Results We analyzed 83 cirrhosis patients with ascites, including 34 patients with hyponatremia. The response rates to tolvaptan in patients with serum sodium <130 mEq/L, 130-135 mEq/L, and >135 mEq/L were 20%, 66%, and 58%, respectively (p=0.22). The serum sodium level was associated with the response to tolvaptan [odds ratio=1.18; 95% confidence interval (CI) =1.02-1.37; p=0.029]. In patients with hyponatremia, the serum sodium level after 1-month tolvaptan treatment was increased compared to baseline (132 mEq/L vs. 136 mEq/L, p=0.006), and an increasing serum sodium level was associated with a lower risk of mortality (hazard ratio=0.85; 95% CI=0.75-0.97; p=0.016). The survival rate was higher in patients with an increase in the serum sodium level after 1 month than in patients with a decreased serum sodium level (p=0.023). Conclusion Tolvaptan treatment was effective in cirrhosis patients with ascites and hyponatremia, but a low serum sodium level was associated with non-responsiveness to tolvaptan. An increased serum sodium level after one-month tolvaptan treatment may positively influence the mortality risk in cirrhosis patients with hyponatremia.
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Predictability of tricuspid annular plane systolic excursion for the effectiveness of tolvaptan in patients with heart failure.
Niwa, T, Waseda, K, Mizuno, T, Nakano, Y, Mukai, K, Wakabayashi, H, Watanabe, A, Ando, H, Takashima, H, Amano, T
Journal of echocardiography. 2017;(3):118-126
Abstract
BACKGROUND There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF. METHODS This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8. RESULTS The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03-1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%). CONCLUSIONS TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.
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Physicians' adherence to guideline-recommended medications in heart failure with reduced ejection fraction: data from the QUALIFY global survey.
Komajda, M, Anker, SD, Cowie, MR, Filippatos, GS, Mengelle, B, Ponikowski, P, Tavazzi, L, ,
European journal of heart failure. 2016;(5):514-22
Abstract
AIMS: To assess physicians' adherence to guideline-recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction. METHODS AND RESULTS QUALIFY is an international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1-15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P < 0.001) and the proportion of women at ≥50% target dose of beta-blockers was lower in those >67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta-blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6 vs. ≥6 months) except for beta-blockers. CONCLUSION This international survey shows that adherence to guideline-recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required.
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SIADH-related hyponatremia in hospital day care units: clinical experience and management with tolvaptan.
De Las Peñas, R, Ponce, S, Henao, F, Camps Herrero, C, Carcereny, E, Escobar Álvarez, Y, Rodríguez, CA, Virizuela, JA, López López, R
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2016;(1):499-507
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Abstract
Hyponatremia (Na ˂ 135 mmol/l) is the most frequent electrolyte disorder in clinical practice, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest cause of hyponatremia in cancer patients. Correcting hyponatremia in these patients can reduce morbidity and mortality, increase the response to anti-cancer agents, and help reduce hospital length of stay and costs. Tolvaptan is an oral medication used to treat SIADH-related hyponatremia patients that needs to be initiated at hospital so patients can have their serum sodium monitored. If tolvaptan could be initiated in hospital day care units (DCUs), performing the same tests, hospitalization could be avoided, quality of life improved, and costs reduced. This is the first publication where a panel of oncologists are sharing their experience and making some recommendations with the use of tolvaptan to treat SIADH-related hyponatremia in DCU after collecting and examining 35 clinical cases with these type of patients. The conclusion from this retrospective observational analysis is that the use of tolvaptan in DCU is safe and effective in the therapeutic management of SIADH-related hyponatremia.
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Effectiveness of Ivabradine Treatment in Different Subpopulations with Stable Angina in Clinical Practice: A Pooled Analysis of Observational Studies.
Werdan, K, Perings, S, Köster, R, Kelm, M, Meinertz, T, Stöckl, G, Müller-Werdan, U
Cardiology. 2016;(3):141-150
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Abstract
OBJECTIVES The efficacy of ivabradine has been demonstrated in different subpopulations of stable angina patients in randomized clinical trials. This study explored its effectiveness in subpopulations seen in clinical practice as they often differ from those of randomized trials. METHODS Data were pooled from three German observational studies with similar inclusion criteria (stable angina and heart rate ≥60 bpm). All patients received 2.5, 5, or 7.5 mg b.i.d. of ivabradine for 4 months, with or without concomitant beta-blocker. Antianginal effectiveness was analyzed in subpopulations defined by gender, age, heart rate, angina severity, use of concomitant beta-blocker, previous percutaneous coronary intervention procedure, and comorbidities (including previous myocardial infarction and diabetes). RESULTS Treatment data were available on 8,555 patients, where therapy with ivabradine was associated with a significant reduction in the frequency of angina attacks and consumption of short-acting nitrates of 87%. Effectiveness was maintained in all investigated subpopulations, with a reduction in antianginal parameters of 82-90%. Clinical status (Canadian Cardiovascular Society class) and quality of life were also improved. Ivabradine was well tolerated in all subgroups. CONCLUSIONS Ivabradine is effective and safe in all subpopulations of angina patients seen in clinical practice, independent of age, comorbidities, and use of beta-blocker.
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Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.
Kadota, M, Ise, T, Yagi, S, Iwase, T, Akaike, M, Ueno, R, Kawabata, Y, Hara, T, Ogasawara, K, Bando, M, et al
International heart journal. 2016;(4):461-5
Abstract
The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.
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Urine osmolarity predicts the body weight-reduction response to tolvaptan in chronic kidney disease patients: a retrospective, observational study.
Iwatani, H, Kawabata, H, Sakaguchi, Y, Yamamoto, R, Hamano, T, Rakugi, H, Isaka, Y
Nephron. 2015;(1):8-12
Abstract
BACKGROUND/AIMS: Tolvaptan, a vasopressin V2 receptor antagonist, promotes the excretion of electrolyte-free water. Patients with heart failure or liver cirrhosis, whose urine osmolarity is high due to increased vasopressin, show a good response to tolvaptan; however, it remains dubious whether tolvaptan is also effective in patients with low urine osmolarity due to decreased renal function. The aim of this study was to investigate whether urine osmolarity predicts the effect of tolvaptan in patients with decreased renal function. METHODS In this retrospective, observational study, 17 overhydrated chronic kidney disease patients with heart failure or liver cirrhosis who were admitted to Osaka University Hospital were included. They were treated with sodium-excreting diuretics first, and then tolvaptan was added. The clinically relevant parameters were evaluated before and after the use of tolvaptan, and they, including urine osmolarity before use of tolvaptan, were compared between the responder group and the non-responder group. The definition of responder was based on the decrease of body weight by ≥5% in one week, which is a more rigorous indicator of the effectiveness of tolvaptan than the increase in urine output. RESULTS The parameter that showed a significant difference between the responder and non-responder groups was urine osmolarity before the use of tolvaptan. The cut-off point derived from the receiver operating characteristic (ROC) curve analysis was 279 mOsm/kg H2O, with sensitivity of 0.86 and specificity of 0.80. CONCLUSIONS In patients with decreased renal function, urine osmolarity before the use of tolvaptan predicted the effectiveness of diuretics in terms of body weight reduction.
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Effects of tolvaptan in the early postoperative stage after heart valve surgery: results of the STAR (Study of Tolvaptan for fluid retention AfteR valve surgery) trial.
Nishi, H, Toda, K, Miyagawa, S, Yoshikawa, Y, Fukushima, S, Kawamura, M, Yoshioka, D, Saito, T, Ueno, T, Kuratani, T, et al
Surgery today. 2015;(12):1542-51
Abstract
PURPOSE The purpose of this study was to assess the efficacy of tolvaptan, a vasopressin V2 receptor antagonist, for the management of postoperative surgical fluid retention after heart valve surgery. METHODS This was a prospective observational study of 64 patients with heart valve disease who underwent valve surgery between 2013 and 2014. Those in the tolvaptan group received tolvaptan in addition to conventional diuretic therapy. The results were compared to the results of 55 patients who underwent heart valve surgery between 2007 and 2010 and received conventional postoperative diuretics alone. RESULTS The time to return to the preoperative BW was significantly shorter in the patients who received tolvaptan (6.1 ± 3.8 vs. 8.7 ± 6.7 days, p < 0.05), while the level of sodium was significantly decreased in the patients who received conventional diuretics. The degree of increase in the creatinine level tended to be smaller in the tolvaptan group. The response to tolvaptan was related to the postoperative degree of BW increase and the preoperative creatinine level. CONCLUSIONS Tolvaptan was effective in treating fluid retention during the early postoperative stage in cardiac surgery patients, without increased renal failure or abnormal electrolyte levels. This new type of diuretic therapy may be a suitable option for postoperative fluid management in patients undergoing cardiac surgery.
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Efficacy of Tolvaptan in Patients with Volume Overload after Cardiac Surgery.
Noguchi, K, Tanaka, M, Katayama, I, Yamabe, T, Yuji, D, Oosiro, N, Sirouzu, M
The heart surgery forum. 2015;(6):E232-6
Abstract
BACKGROUND The vasopressin type 2 receptor antagonist tolvaptan (TLV) has recently become available for treating congestion. However, there is no evidence confirming the efficacy of TLV for patients with volume overload after cardiac surgery. Here, we retrospectively studied the efficacy of TLV in patients with volume overload after cardiac surgery. METHODS We enrolled a total of 39 patients who had volume overload after cardiac surgery and who were treated with our protocol of body fluid management. The primary endpoint of this study was to evaluate the hospitalization period, while the secondary endpoints were to estimate adverse events such as hypotension, electrolyte abnormality, presence or absence of renal dysfunction and liver damage, and the incidence of atrial fibrillation (AF). RESULTS The hospitalization period of the T (TLV) and C (furosemide and spironolactone) groups was 12.3 ± 2.6 days and 14.7 ± 4.4 days, respectively (P = .044), the mean urine volume was 2761.5 ± 850.3 mL/day and 2205.2 ± 598.5 mL/day, respectively (P = .024), and the incidence of postoperative AF after diuretics administration was 2/19 (11%) and 9/17 (52%), respectively. CONCLUSION TLV successfully and rapidly improved organ congestion without causing hemodynamic abnormalities (hypotension, arrhythmia development), electrolyte abnormality, liver damage or renal dysfunction, thus significantly reducing the period of hospitalization.
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Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).
Kinugawa, K, Inomata, T, Sato, N, Yasuda, M, Shimakawa, T, Bando, K, Mizuguchi, K
International heart journal. 2015;(2):137-43
Abstract
The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80). The results showed that the effectiveness of tolvaptan in the aged patients was similar to that in U-80 patients. In the safety profile, the incidence rate of thirst was lower in the aged patients than that in U-80 patients (9.6% versus 11.6%, P = 0.0023). Furthermore, the incidence of hypernatremia, defined as ≥ 150 mEq/L in aged patients, was comparable with that in U-80 patients (2.9% versus 3.6%, respectively, P = 0.3657). Based on these findings, tolvaptan has similar effectiveness and safety profiles in aged patients compared with U-80 patients. In addition, we found that a higher starting dose of tolvaptan was markedly associated with the occurrence of hypernatremia exclusively in the aged population; therefore, we recommend that tolvaptan should be started at lower doses in aged patients.