Efficacy of Sacubitril/Valsartan in the Treatment of Patients with Coronary Artery Disease Complicated by Heart Failure
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摘要:
目的 探讨沙库巴曲缬沙坦（sacubitril/valsartan，S/V）在冠心病（coronary heart disease，CHD）合并心力衰竭（heart failure，HF）住院患者中的短期疗效及安全性。 方法 采用前瞻性、非随机、开放标签对照设计，纳入2020年1月至2023年12月本院收治的CHD合并HF患者65例。对照组（n = 33）接受常规血管紧张素转换酶抑制剂（angiotensin-converting enzyme inhibitor，ACEI）或血管紧张素Ⅱ受体拮抗剂（angiotensin receptor blocker，ARB）治疗；用药组（n = 32）在停用ACEI/ARB 36小时后改用S/V。观察治疗21天前后心功能指标、氧化应激指标、血流动力学参数、炎性因子、生活质量评分及不良反应情况。 结果 与对照组相比，用药组治疗21天后左心射血分数（left ventricular ejection fraction，LVEF）升高，左心室收缩末期内径（left ventricular end-systolic diameter，LVESd）及舒张末期内径（left ventricular end-systolic diameter，LVDd）降低（P < 0.05）；超氧化物歧化酶（superoxide dismutase，SOD）水平升高，丙二醛（malondialdehyde，MDA）水平下降（P < 0.05）；心指数（cardiac index，CI）及心排血量（cardiac output，CO）增加（P < 0.05）；血清肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素6（interleukin-6，IL-6）及C反应蛋白（C-reactive protein，CRP）水平下降（P < 0.05）；SF-36生活质量评分升高（P < 0.05）。不良反应发生率在两组间差异有统计学意义（P < 0.05）。 结论 S/V可在短期内改善CHD合并HF住院患者的心功能、氧化应激水平、血流动力学及炎症反应。 Abstract:Objective To investigate the short-term efficacy and safety of sacubitril/valsartan （S/V） in patients with coronary heart disease （CHD） complicated by heart failure （HF） during hospitalization. Methods A prospective, non-randomized, open-label controlled design was used. A total of 65 patients with CHD complicated by HF who were admitted to our hospital from January 2020 to December 2023 were enrolled. The control group （n = 33） received conventional ACEI/ARB therapy, while the treatment group （n = 32） switched to S/V after discontinuing ACEI/ARB for 36 hours. Heart function, oxidative stress markers, hemodynamic parameters, inflammatory factors, quality of life scores, and adverse reactions were observed and compared before and after 21 days of treatment. Results Compared with the control group, the treatment group showed significant improvements in left ventricular ejection fraction （LVEF）, left ventricular end-systolic diameter （LVESd）, and left ventricular end-diastolic diameter （LVEDd） after 21 days （P < 0.05）. Superoxide dismutase （SOD） levels increased, while malondialdehyde （MDA） levels decreased （P < 0.05）. Cardiac index （CI） and cardiac output （CO） increased （P < 0.05）, and serum levels of tumor necrosis factor-alpha （TNF-α）, interleukin-6 （IL-6）, and C-reactive protein （CRP） decreased （P < 0.05）. The SF-36 quality of life score significantly improved （P < 0.05）. The incidence of adverse reactions was significantly lower in the treatment group compared with the control group （P < 0.05）. Conclusion S/V can improve cardiac function, oxidative stress, hemodynamics, and inflammatory response in hospitalized patients with CHD complicated by HF in the short term. -
Key words:
- Coronary heart disease /
- Heart failure /
- Sacubitril/valsartan /
- Heart function /
- Oxidative stress /
- Inflammation
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表 1 两组患者基线资料比较
Table 1. Comparison of baseline characteristics between the two groups
项目 对照组 （n=33） 用药组 （n=32） χ2/t值 P值 性别（男/女） 18/15 17/15 0.021 0.885 年龄（岁） 67.91 ± 5.93 67.94 ± 5.99 0.021 0.984 年龄范围（岁） 54～80 53～83 − − 冠心病病程（年） 10.64 ± 3.85 10.50 ± 3.33 0.161 0.873 冠心病病程范围 3～17 4～19 − − 心衰病程（年） 2.03 ± 0.77 2.00 ± 0.88 0.147 0.884 心衰病程范围 1～4 0～4 − − NYHA分级（II/III/IV） 12/15/6 11/16/5 0.132 0.936 
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表 2 对照组与用药组患者心功能指标比较（$\bar x \pm s $，n = 33）
Table 2. Comparison of heart function parameters between the control group and the treatment group （$\bar x \pm s $，n = 33）
指标 时间 对照组 用药组 组间t 组间P LVEF（%） 0 d 33.56 ± 6.35 33.99 ± 4.72 −0.310 0.757 21 d 35.99 ± 5.35 38.93 ± 6.20 −2.044 0.045* 组内t 1.425 5.018 — — 组内P 0.160 <0.001* — — LVESd（mm） 0 d 40.43 ± 4.10 39.68 ± 3.46 0.798 0.428 21 d 37.19 ± 6.42 34.62 ± 4.01 1.942 0.057 t 1.729 6.198 — — P 0.091 <0.001* — — LVEDd（mm） 0 d 64.70 ± 5.89 64.67 ± 4.53 0.023 0.982 21 d 59.27 ± 13.53 53.52 ± 9.63 1.979 0.053 t 1.932 7.247 — — P 0.062 <0.001* — — 与对照组同期比较，*P < 0.05；同组治疗前后比较见表内。
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表 3 对照组与用药组患者氧化应激指标比较（$\bar x \pm s $）
Table 3. Comparison of oxidative stress parameters between the control group and the treatment group （$\bar x \pm s $）
指标 时间 对照组 （n=33） 用药组 （n=32） 组间t 组间P SOD （U/mL） 0 d 56.81 ± 6.56 55.77 ± 5.16 0.726 0.470 21 d 62.61 ± 15.89 69.64 ± 12.39 −2.189 0.033* 组内t 2.362 6.880 — — 组内P 0.022* <0.001* — — MDA （μmol/L） 0 d 9.15 ± 1.01 39.68 ± 3.46 0.321 0.750 21 d 8.25 ± 2.04 34.62 ± 4.01 2.382 0.021* 组内t 2.398 7.200 — — 组内P 0.021* <0.001* — — 与对照组同期比较，*P < 0.05；同组治疗前后比较见表内。
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表 4 对照组与用药组患者血流动力学指标比较（$\bar x \pm s $）
Table 4. Comparison of hemodynamic parameters between the control group and the treatment group （$\bar x \pm s $）
指标 时间 对照组 （n=33） 用药组 （n=32） 组间t 组间P CI （L/min·m2） 0 d 1.89 ± 0.68 1.94 ± 0.78 −0.289 0.774 21 d 2.17 ± 0.44 2.42 ± 0.47 −2.251 0.015* 组内t 1.970 2.990 — — 组内P 0.029* 0.002* — — CO （L/min） 0 d 3.22 ± 0.51 3.18 ± 0.69 0.271 0.787 21 d 3.51 ± 0.61 3.82 ± 0.59 −2.126 0.029* 组内t 2.073 4.041 — — 组内P 0.022* <0.001* — — 与对照组同期比较，*P < 0.05
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表 5 对照组与用药组患者血清炎症因子水平比较（$\bar x \pm s $）
Table 5. Comparison of serum inflammatory factors between the control group and the treatment group （$\bar x \pm s $）
指标 时间 对照组 （n=33） 用药组 （n=32） 组间t值 组间P值 TNF-α （ng/L） 0 d 15.40 ± 4.29 15.24 ± 4.14 0.153 0.879 21 d 13.44 ± 2.53 11.99 ± 3.03 2.091 0.041* 组内t 2.205 4.155 — — 组内P 0.031* <0.001* — — IL-6 （ng/L） 0 d 39.70 ± 5.65 39.11 ± 3.83 0.494 0.623 21 d 36.55 ± 7.28 32.08 ± 7.01 2.522 0.014* 组内t 1.853 4.408 — — 组内P 0.069 <0.001* — — CRP （mg/L） 0 d 5.15 ± 0.55 5.09 ± 0.55 0.440 0.662 21 d 4.81 ± 0.74 4.52 ± 0.76 1.558 0.124 组内t 2.203 3.236 — — 组内P 0.031* 0.002* — — 与对照组同期比较，*P < 0.05。
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表 6 对照组与用药组患者生活质量评分比较（$\bar x \pm s $）
Table 6. Comparison of quality of life scores between the control group and the treatment group （$\bar x \pm s $）
指标 时间 对照组 （n=33） 用药组 （n=32） 组间t值 组间P值 心理功能 0 d 59.87 ± 5.61 59.72 ± 5.38 0.120 0.905 21 d 66.79 ± 16.81 73.35 ± 14.18 −1.703 0.094* 组内t −2.243 −5.084 — — 组内P 0.031* <0.001* — — 社会功能 0 d 62.95 ± 5.52 62.19 ± 5.35 0.579 0.564 21 d 66.92 ± 11.42 75.93 ± 14.60 −2.766 0.008* 组内t −1.798 −4.999 — — 组内P 0.079 <0.001* — — 躯体功能 0 d 60.84 ± 4.49 60.62 ± 4.38 0.201 0.841 21 d 64.69 ± 11.17 72.40 ± 16.53 −2.197 0.032* 组内t −1.837 −3.897 — — 组内P 0.073 <0.001* — — 物质生活 0 d 62.00 ± 4.24 61.71 ± 5.06 0.251 0.803 21 d 68.60 ± 15.30 75.41 ± 14.08 −1.868 0.066 组内t −2.388 −5.180 — — 组内P 0.022* <0.001* — — 与对照组同期比较，*P < 0.05。
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表 7 对照组与用药组患者不良反应发生情况比较[n（%）]
Table 7. Comparison of adverse reaction occurrence between the control group and the treatment group [n（%）]
项目 对照组 （n=33） 用药组 （n=32） P值 口干n（%） 3 （9.09） 1 （3.13） 0.613 咳嗽n（%） 3 （9.09） 0 （0.00） 0.242 心悸n（%） 2 （6.06） 0 （0.00） 0.492 低血压n（%） 2 （6.06） 0 （0.00） 0.492 总发生率（%） 10 （30.30） 1 （3.13） 0.020* 与对照组比较，*P < 0.05。
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