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维司力农的临床特征

Clinical characteristics of vesnarinone.

作者信息

Feldman Arthur M

机构信息

Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

出版信息

Drug Saf. 2004;27 Suppl 1:1-9. doi: 10.2165/00002018-200427001-00002.

Abstract

Congestive heart failure is a common condition with a poor prognosis. Its high rates of morbidity and mortality produce a huge societal burden. Current pharmacological treatment approaches are based on angiotensin-converting enzyme inhibitors, diuretics and digoxin, but up to 5% of patients may have refractory disease with persistent symptoms at rest. Such patients with advanced-stage disease may be candidates for treatment with the novel agent vesnarinone, a mixed phosphodiesterase inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. Vesnarinone improves ventricular performance most in patients with the worst degree of heart failure. However, before the initiation of vesnarinone therapy, risk-benefit profiles in individual patients should be considered, because in two large-scale studies [i.e. of the high dosage used in the Vesnarinone Study Group Trial (VSGT), and of both dosages used in the Vesnarinone Trial (VEST)] a dose-dependent increase in mortality was identified for vesnarinone 30-120 mg/day. The two studies also found significant vesnarinone-induced, short-term improvements in quality of life (QOL) in patients with refractory end-stage heart failure. Such patients are the most willing to trade-off a slightly increased risk of mortality for improved QOL. It is thus in these patients with refractory end-stage heart failure that vesnarinone may ultimately establish an important treatment role. However, detailed further investigation of the overall place of vesnarinone in heart failure management, with particular reference to the clinical potential of vesnarinone plus beta-blocker combination therapy, for example, is certainly warranted.

摘要

充血性心力衰竭是一种常见疾病,预后较差。其高发病率和死亡率给社会带来了巨大负担。目前的药物治疗方法主要基于血管紧张素转换酶抑制剂、利尿剂和地高辛,但高达5%的患者可能患有难治性疾病,休息时仍有持续症状。这类晚期疾病患者可能是新型药物维司力农治疗的候选者,维司力农是一种混合磷酸二酯酶抑制剂和离子通道调节剂,具有适度的、剂量依赖性的正性肌力活性,但负性变时活性极小。维司力农在心力衰竭程度最严重的患者中对心室功能的改善最为显著。然而,在开始维司力农治疗之前,应考虑个体患者的风险效益情况,因为在两项大规模研究中[即维司力农研究组试验(VSGT)中使用的高剂量,以及维司力农试验(VEST)中使用的两种剂量],发现维司力农每日30 - 120毫克会导致剂量依赖性的死亡率增加。这两项研究还发现,维司力农能使难治性终末期心力衰竭患者的生活质量(QOL)在短期内有显著改善。这类患者最愿意为提高生活质量而权衡略有增加的死亡风险。因此,正是在这些难治性终末期心力衰竭患者中,维司力农最终可能确立重要的治疗地位。然而,对维司力农在心力衰竭管理中的整体地位进行详细的进一步研究,特别是参考维司力农加β受体阻滞剂联合治疗的临床潜力等,肯定是有必要的。

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