血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效及安全性评价

目的：探讨血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效及安全性评价。方法：选自我院于2014年1月~2015年12月肝硬化并低钠血症患者72例,按照随机数字表法随机分为观察组36例与对照组36例。对照组采用常规治疗,观察组在对照组基础上结合托伐普坦治疗。两组疗程均为7d。比较两组治疗疗效,治疗前后血钠、尿钠、血尿酸、肾功能指标水平变化及药物不良反应情况。结果：观察组总有效率(88.89%)高于对照组(66.67%)(P<0.05);两组血钠、尿钠、血尿酸水平治疗后增加(P<0.05);观察组血钠、尿钠、血尿酸水平治疗后高于对照组(P<0.05);两组血清BUN和Cr水平治疗前比较无统计学差异(P>0.05);两组血清BUN和Cr水平治疗后前后无变化(P>0.05);两组均未见严重不良反应。结论：血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效显著,且安全性良好,值得研究。     

Advances in chemical pharmacotherapy for managing acute decompensated heart failure

Introduction: Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful.

Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature.

Expert opinion: Currently, popular therapies like diuretics, vasodilators, and inotropes offer symptomatic relief but do not provide survival benefit. Although multiple medications targeting novel pathways in ADHF were studied extensively, they failed to show either symptomatic or mortality benefit in available randomized trials. Improving our understanding of the complex pathophysiology of ADHF along with designing studies which include patients who are more representative of the real-world heart failure population, standardizing methods for endpoint assessment, and evaluating the role on novel biomarkers of organ dysfunction is important to improve ADHF research. Enhancing preventive strategies like improving baseline therapy in chronic heart failure patients and developing strategies for early identification of ADHF are important as our quest for innovative ADHF pharmacotherapy continues.     

Is tolvaptan indicated for refractory oedema in nephrotic syndrome?

Tolvaptan is useful for correcting dilutional hyponatraemia because of its aquaretic effect. On the other hand, there is a distinct lack of data regarding tolvaptan‐induced natriuresis, although previous studies have demonstrated improvement of congestive symptoms and signs in heart failure patients following tolvaptan treatment. Here, we report the case of a 47‐year‐old man diagnosed with minimal change nephrotic syndrome and whose refractory oedema was immediately controlled by tolvaptan before steroid response was induced. With tolvaptan treatment, patient urine output increased dramatically to approximately 5.5 L/day and body weight decreased by 9 kg over 5 days. Interestingly, urine sodium concentration, fractional excretion of sodium and urine osmolality all increased in response to tolvaptan administration. However, serum sodium concentration was maintained within the normal range, and mild azotaemia was corrected. Tolvaptan was discontinued after 11 days when heavy proteinuria and generalized oedema had been resolved. We discuss the potential mechanisms by which V₂ receptor antagonists may stimulate natriuresis in the kidney. In conclusion, tolvaptan may be useful as an adjunctive treatment for oedematous disorders.     

Hypercholesterolemia Dietary and Pharmacotherapy

ABSTRACT

Objectives: To estimate the cost difference associated with tolvaptan treatment vs. fluid restriction (FR) among hospitalized patients with heart failure (HF) and hyponatremia (HN) based on a real-world registry of HN patients.

Methods: An Excel-based economic model was developed to evaluate the cost impact of tolvaptan treatment vs. FR. Model input for hospital length of stay (LOS) was based on published data from the Hyponatremia Registry (HNR). Based on HNR data, tolvaptan-treated patients had a 2-day (median) shorter LOS compared to FR. Real-world effectiveness of tolvaptan treatment from the HNR was applied to a national sample of inpatients visits from the Premier Hospital database to estimate the potential LOS-related cost difference between tolvaptan treatment and FR. A one-way sensitivity and multivariable Monte Carlo sensitivity analysis were conducted.

Results: Economic modeling results of the base-case analysis indicated that among hospitalized patients with HF, the hospital cost per admission, not including HN drug cost, was $3453 lower among patients treated with tolvaptan vs. FR, due to the shorter LOS associated with tolvaptan treatment. At wholesale acquisition cost of $362 per day and an average treatment duration of 3.2 days, the pharmacy cost of tolvaptan treatment per admission was estimated at $1157. Thus, after factoring the decrease in hospital medical costs and increase in pharmacy costs associated with tolvaptan treatment, results indicated a cost-offset opportunity of –$2296 per admission for patients treated with tolvaptan versus FR. Results of the sensitivity analyses were consistent with the base-case analysis.

Limitations: The model derives inputs from real-world observational data. No causal relationship can be inferred from this analysis.

Conclusions: Based on this economic analysis, tolvaptan treatment vs. FR among hospitalized patients with HF and HN may be associated with lower hospital-related costs, which offset the increase in pharmacy costs associated with tolvaptan treatment.     

Plasma concentration and efficacy of tolvaptan in cirrhotic patients with refractory ascites

To investigate the relationship between the exposure and efficacy of tolvaptan, we measured pharmacokinetics of total drug at 7 days after repeated doses of 3.75 mg/day tolvaptan in 16 patients with hepatic edema. Nine patients (56.3%) were responders, which were defined as those with body weight reduction of >1.5 kg/week. Serum albumin levels were significantly lower in responders than in non-responders (P = 0.031). However, the pharmacokinetics varied greatly among individuals and was not relevant to the clinical response.     

抗利尿激素不适当分泌综合征18例临床分析及治疗策略

目的 通过对抗利尿激素不适当分泌综合征（SIADH）临床特点总结分析及对托伐普坦治疗SIADH临床疗效观察,分享治疗体会,提高对该疾病诊治水平,减少漏诊及误诊率。方法 回顾分析2011年10月至2013年4月我院收治的18例SIADH患者临床表现、化验结果及治疗预后情况,结合国内外文献进行讨论。结果 18例确诊SIADH患者中,94%为恶性肿瘤患者,其中28%为小细胞肺癌。不同病因患者临床表现及实验室指标无明显差异。但年龄小于65岁者显示出诊断时血钠水平更低趋势。15例患者通过限水、利尿,血钠恢复正常。2例小细胞肺癌及1例继发性肺结核患者上述治疗无效,予以托伐普坦15mg qd治疗,48h后血钠恢复正常。结论 SIADH其临床表现无特异性,早诊断、早治疗是提高救治成功率的关键。当限水、利尿仍不能纠正低钠血症时,口服托伐普坦治疗安全有效。     

托伐普坦治疗老年重症心力衰竭伴中重度低钠血症有效性和安全性研究

目的 探讨托伐普坦治疗老年重症心力衰竭伴中重度低钠血症有效性和安全性研究。方法 选取2013年1月-2017年12月在空军军医大学唐都医院诊治的老年重症心力衰竭伴中重度低钠血症患者40例,随机分为对照组（20例）和观察组（20例）,对照组患者采用常规方法治疗,观察组患者在常规方法的治疗基础上给予托伐普坦治疗,连续治疗7 d后比较两组患者治疗前后左室射血分数（LVEF）、左室舒张末期压力（LVEDP）、肺动脉压（PAP）、心输出量（CO）、血钠、血渗透压及24 h尿量及不良反应的发生率。结果 治疗后,两组患者的LVEF和CO显著升高,而LVEDP和PAP显著降低,差异具有统计学意义（P<0.05）;且观察组患者的LVEF和CO显著高于对照组,而LVEDP和PAP显著低于对照组,差异具有统计学意义（P<0.05）。治疗后,两组患者的血钠、血渗透压及24 h尿量均明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组患者的血钠、血渗透压及24 h尿量均显著高于对照组,差异具有统计学意义（P<0.05）。观察组患者不良反应发生率为15.00%,对照组患者不良反应发生率为25.00%,差异无统计学意义。结论 托伐普坦治疗老年重症心力衰竭伴中重度低钠血症的临床效果较好,可显著改善患者的心功能及血钠值,安全性较高。