Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
Ann Pharmacother. 2010 Apr;44(4):680-7. doi: 10.1345/aph.1M660.
To evaluate acute hemodynamic, short-term, and long-term effects of vasopressin antagonists in patients with heart failure (HF).
Searches of the PubMed database (1966-February 2010) were conducted. Search terms included AVP receptor antagonist, CHF, tolvaptan, conivaptan, lixivaptan, HF, and hyponatremia. Manufacturers' prescribing information, manufacturer Web site searches, and searches made on www.clinicaltrials.gov were also included.
All clinical trials identified from the reference search and data sources were reviewed. Articles were included if they were relevant to short-term and long-term outcomes of patients with HF who were treated with vasopressin antagonists.
Trials of conivaptan, tolvaptan, and lixivaptan were evaluated. The evidence indicates that all agents increase urine output >10 mL/h, and conivaptan and tolvaptan decrease pulmonary capillary wedge pressure (-2.6 +/- 0.7, -5.4 +/- 0.7, and -4.6 +/- 0.7 mm Hg for placebo, conivaptan 20 mg, and conivaptan 40 mg, respectively; -5.67 +/- 4.58 to -6.38 +/- 4.12 mmHg for tolvaptan, and -4.16 +/- 4.57 mm Hg for placebo) in patients with HF. Both of these changes occur without inducing electrolyte abnormalities or renal dysfunction. Trials with conivaptan in acute HF have not demonstrated a benefit in cardiac index, mean arterial pressure, or vascular resistance. Data from clinical trials indicate that tolvaptan may decrease dyspnea (p < 0.05) and pedal edema (p < 0.001). To date, no large-scale trials of any agent have demonstrated an improvement in left ventricular systolic function, rehospitalization, worsening HF, or death.
Vasopressin antagonists cannot be considered routine pharmacotherapy for HF. Further, conivaptan should not be used for the treatment of acute HF. There is not enough literature to advocate for or against the use of lixivaptan in patients with HF. Tolvaptan may be considered for the treatment of hyponatremia.
评估血管加压素拮抗剂在心力衰竭（HF）患者中的急性血流动力学、短期和长期疗效。
对 PubMed 数据库（1966 年-2010 年 2 月）进行了检索。检索词包括 AVP 受体拮抗剂、CHF、托伐普坦、康维普坦、利昔普坦、HF 和低钠血症。还包括制造商的处方信息、制造商网站搜索以及在 www.clinicaltrials.gov 上的搜索。
对参考检索和资料来源中确定的所有临床试验进行了审查。如果文章与接受血管加压素拮抗剂治疗的 HF 患者的短期和长期结局相关，则将其纳入。
评估了康维普坦、托伐普坦和利昔普坦的试验。证据表明，所有药物均使尿量增加>10ml/h，康维普坦和托伐普坦降低肺毛细血管楔压（安慰剂分别为-2.6±0.7、-5.4±0.7 和-4.6±0.7mmHg；康维普坦 20mg 和 40mg 分别为-5.67±4.58 至-6.38±4.12mmHg；托伐普坦为-4.16±4.57mmHg）。这些变化均不会引起电解质异常或肾功能障碍。急性 HF 中康维普坦的试验并未显示心指数、平均动脉压或血管阻力的改善。临床试验数据表明，托伐普坦可能减轻呼吸困难（p<0.05）和足水肿（p<0.001）。迄今为止，任何药物的大型试验均未显示左心室收缩功能、再住院、HF 恶化或死亡的改善。
血管加压素拮抗剂不能作为 HF 的常规药物治疗。此外，康维普坦不应用于治疗急性 HF。目前，尚无足够的文献支持或反对在 HF 患者中使用利昔普坦。托伐普坦可考虑用于治疗低钠血症。
