Keating Gillian M, Goa Karen L
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 2003;63(1):47-70. doi: 10.2165/00003495-200363010-00004.
Nesiritide (Natrecor) is a recombinant form of human B-type (brain) natriuretic peptide that has beneficial vasodilatory, natriuretic, diuretic and neurohormonal effects. The drug is administered intravenously for the management of patients with decompensated congestive heart failure (CHF). In the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study, patients hospitalised with acute decompensated CHF who received nesiritide had significantly greater mean reductions from baseline in pulmonary capillary wedge pressure 3 hours after starting treatment than nitroglycerin or placebo recipients (-5.8 vs -3.8 and -2 mm Hg, respectively); all patients also received standard therapy (e.g. intravenous diuretics). Improvements in other haemodynamic parameters were also seen in nesiritide recipients. In addition, significantly more nesiritide than placebo recipients reported an improvement in dyspnoea after 3 hours' treatment in VMAC, whereas there was no significant difference between nitroglycerin and placebo recipients. Improvements in global clinical status, dyspnoea and fatigue were also seen with nesiritide in another active-comparator study and in a placebo-controlled study. In VMAC, there was no significant difference between nesiritide and nitroglycerin recipients in 6-month mortality. In the other active-comparator trial, 6-month mortality was significantly lower in recipients of nesiritide 0.015 micro g/kg/min than in dobutamine recipients (although mortality was not a prespecified endpoint and this result should be interpreted with caution). In this same study, the 21-day all-cause hospital readmission rate was significantly lower with nesiritide 0.015 micro g/kg/min than with dobutamine and the duration of active drug treatment was significantly shorter with nesiritide than with dobutamine. Nesiritide is generally well tolerated. In VMAC, significantly more adverse events occurred with nitroglycerin than with nesiritide. The most common adverse events reported during the first 24 hours of therapy in nesiritide and nitroglycerin recipients included general pain, abdominal pain, catheter-related pain, headache, nausea, asymptomatic and symptomatic hypotension, nonsustained ventricular tachycardia and angina pectoris. Most episodes of symptomatic hypotension resolved spontaneously or after an intravenous volume challenge of </=250 ml. In addition, nesiritide does not appear to be proarrhythmic.
Short-term intravenous infusion of nesiritide is associated with haemodynamic and symptomatic improvements in patients with acutely decompensated CHF. Nesiritide may offer tolerability and practical advantages over currently used vasodilators, inodilators and inotropes in this condition; in particular, nesiritide does not appear to have proarrhythmic effects. Nesiritide also appears to be effective and well tolerated in patients receiving concomitant beta-blocker therapy and in patients with renal insufficiency. Thus, nesiritide is a suitable first-line option for the treatment of patients with acutely decompensated CHF and is a welcome addition in an area where intravenous agents are few.
奈西立肽(诺欣妥)是重组人B型(脑)利钠肽,具有有益的血管舒张、利钠、利尿和神经激素作用。该药物通过静脉给药,用于治疗失代偿性充血性心力衰竭(CHF)患者。在急性充血性心力衰竭管理中的血管舒张(VMAC)研究中,因急性失代偿性CHF住院的患者,接受奈西立肽治疗后,开始治疗3小时后肺毛细血管楔压较基线的平均降低幅度显著大于接受硝酸甘油或安慰剂的患者(分别为-5.8 vs -3.8和-2 mmHg);所有患者均接受标准治疗(如静脉利尿剂)。奈西立肽治疗的患者在其他血流动力学参数方面也有改善。此外,在VMAC研究中,治疗3小时后,报告呼吸困难改善的奈西立肽治疗患者显著多于安慰剂治疗患者,而硝酸甘油治疗患者与安慰剂治疗患者之间无显著差异。在另一项活性对照研究和一项安慰剂对照研究中,奈西立肽治疗也使整体临床状况、呼吸困难和疲劳得到改善。在VMAC研究中,奈西立肽治疗患者与硝酸甘油治疗患者的6个月死亡率无显著差异。在另一项活性对照试验中,奈西立肽0.015 μg/kg/min治疗患者的6个月死亡率显著低于多巴酚丁胺治疗患者(尽管死亡率不是预先设定的终点,该结果应谨慎解读)。在同一研究中,奈西立肽0.015 μg/kg/min治疗患者的21天全因住院再入院率显著低于多巴酚丁胺治疗患者,且奈西立肽治疗的活性药物治疗持续时间显著短于多巴酚丁胺治疗。奈西立肽一般耐受性良好。在VMAC研究中,硝酸甘油治疗患者发生显著更多不良事件。奈西立肽和硝酸甘油治疗患者在治疗的前24小时报告的最常见不良事件包括全身疼痛、腹痛、导管相关疼痛、头痛、恶心、无症状和有症状低血压、非持续性室性心动过速和心绞痛。大多数有症状低血压发作可自发缓解或在静脉输注≤250 ml液体后缓解。此外,奈西立肽似乎无促心律失常作用。
短期静脉输注奈西立肽可使急性失代偿性CHF患者的血流动力学和症状得到改善。在这种情况下奈西立肽可能比目前使用的血管扩张剂、血管扩张性正性肌力药和正性肌力药具有更好的耐受性和实际优势;特别是,奈西立肽似乎没有促心律失常作用。奈西立肽在接受β受体阻滞剂联合治疗的患者和肾功能不全患者中似乎也有效且耐受性良好。因此,奈西立肽是治疗急性失代偿性CHF患者的合适一线选择,是静脉用药较少领域中一个受欢迎的补充药物。