Bozkurt B, Torre-Amione G, Warren M S, Whitmore J, Soran O Z, Feldman A M, Mann D L
Winters Center For Heart Failure Research, Department of Medicine, Veterans Administration Medical Center, Houston, TX 77030, USA.
Circulation. 2001 Feb 27;103(8):1044-7. doi: 10.1161/01.cir.103.8.1044.
Previously, we showed that tumor necrosis factor (TNF) antagonism with etanercept, a soluble TNF receptor, was well tolerated and that it suppressed circulating levels of biologically active TNF for 14 days in patients with moderate heart failure. However, the effects of sustained TNF antagonism in heart failure are not known.
We conducted a randomized, double-blind, placebo-controlled, multidose trial of etanercept in 47 patients with NYHA class III to IV heart failure. Patients were treated with biweekly subcutaneous injections of etanercept 5 mg/m(2) (n=16) or 12 mg/m(2) (n=15) or with placebo (n=16) for 3 months. Doses of 5 and 12 mg/m(2) etanercept were safe and well tolerated for 3 months. Treatment with etanercept led to a significant dose-dependent improvement in left ventricular (LV) ejection fraction and LV remodeling, and there was a trend toward an improvement in patient functional status, as determined by clinical composite score.
Treatment with etanercept for 3 months was safe and well-tolerated in patients with advanced heart failure, and it resulted in a significant dose-dependent improvement in LV structure and function and a trend toward improvement in patient functional status.
此前，我们发现使用可溶性肿瘤坏死因子（TNF）受体依那西普拮抗TNF耐受性良好，且在中度心力衰竭患者中，它可使具有生物活性的TNF循环水平在14天内受到抑制。然而，持续性TNF拮抗在心力衰竭中的作用尚不清楚。
我们对47例纽约心脏协会（NYHA）心功能III至IV级的心力衰竭患者进行了一项依那西普的随机、双盲、安慰剂对照、多剂量试验。患者接受为期3个月的每两周一次皮下注射依那西普5mg/m²（n = 16）或12mg/m²（n = 15）或安慰剂（n = 16）治疗。5mg/m²和12mg/m²剂量的依那西普在3个月内安全且耐受性良好。依那西普治疗导致左心室（LV）射血分数和LV重塑有显著的剂量依赖性改善，并且根据临床综合评分确定，患者功能状态有改善趋势。
对于晚期心力衰竭患者，使用依那西普治疗3个月安全且耐受性良好，并且导致LV结构和功能有显著的剂量依赖性改善以及患者功能状态有改善趋势。
