白细胞介素-1 阻断剂治疗射血分数保留的心力衰竭患者。
IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction.
机构信息
Division of Cardiology, Virginia Commonwealth University Pauley Heart Center, Richmond (B.W.V.T., C.R.T., J.C., S.C., D.K., M.G.D.B., H.B., G.W., M.V., C.O.-E., N.A.A., D.D., A.A.).
Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond (B.W.V.T., L.B., G.W., D.D.).
出版信息
Circ Heart Fail. 2018 Aug;11(8):e005036. doi: 10.1161/CIRCHEARTFAILURE.118.005036.
Background Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction. Methods and Results Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (Vo), ventilatory efficiency (V/Vco slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak Vo or V/Vco slope between groups at baseline. Peak Vo was not changed after 12 weeks of anakinra (from 13.6 [11.8-18.0] to 14.2 [11.2-18.5] mL·kg·min, P=0.89), or placebo (14.9 [11.7-17.2] to 15.0 [13.8-16.9] mL·kg·min, P=0.40), without significant between-group differences in changes at 12 weeks (-0.4 [95% CI, -2.2 to +1.4], P=0.64). V/Vco slope was also unchanged with anakinra (from 28.3 [27.2-33.0] to 30.5 [26.3-32.8], P=0.97) or placebo (from 31.6 [27.3-36.9] to 31.2 [27.8-33.4], P=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, -1.8 to +4.3], P=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline ( P=0.026 and P=0.022 versus placebo [between-group analysis], respectively). Conclusions Treatment with anakinra for 12 weeks failed to improve peak Vo and V/Vco slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02173548.
背景
增强的炎症可能导致射血分数保留的心力衰竭患者运动不耐受。本研究的目的是确定白细胞介素（IL）-1 阻断剂阿那白滞素是否能改善射血分数保留的心力衰竭患者的心肺功能。
方法和结果
31 例射血分数保留的心力衰竭且 C 反应蛋白（CRP）>2mg/L 的患者被随机分为阿那白滞素（皮下注射 100mg 每日一次，N=21）或安慰剂（N=10）治疗 12 周。我们在第 4、12 和 24 周测量峰值耗氧量（Vo）、通气效率（V/Vco 斜率）和高敏 CRP 和 NT-proBNP（N 端脑利钠肽前体）。28 例患者完成了≥2 次就诊，18 例女性（64%），27 例（96%）肥胖。两组在基线时的峰值 Vo 或 V/Vco 斜率无差异。阿那白滞素治疗 12 周后，峰值 Vo 无变化（从 13.6[11.8-18.0]到 14.2[11.2-18.5]mL·kg·min，P=0.89），或安慰剂（从 14.9[11.7-17.2]到 15.0[13.8-16.9]mL·kg·min，P=0.40），12 周时无显著组间差异（-0.4[95%CI，-2.2 至+1.4]，P=0.64）。阿那白滞素（从 28.3[27.2-33.0]到 30.5[26.3-32.8]，P=0.97）或安慰剂（从 31.6[27.3-36.9]到 31.2[27.8-33.4]，P=0.78）治疗后，V/Vco 斜率也无变化，12 周时无显著组间差异（+1.2[95%CI，-1.8 至+4.3]，P=0.97）。在接受阿那白滞素治疗的患者中，与基线相比，4 周时高敏 CRP 和 NT-proBNP 水平降低（P=0.026 和 P=0.022，与安慰剂相比[组间分析]）。
结论
在一组肥胖射血分数保留的心力衰竭患者中，阿那白滞素治疗 12 周未能改善峰值 Vo 和 V/Vco 斜率。阿那白滞素治疗后 CRP 和 NT-proBNP 的有利趋势值得在未来的研究中进一步探索。
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