RESULTS: The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088).
CONCLUSIONS: We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients.
结果:该研究为IV期,prospective,随机化,双盲,NYHAII-III级心力衰竭(HF)且左心室(LV)射血分数(EF)≤35%的患者的平行组研究。在为期6周的磨合期中,所有患者均接受缬沙坦治疗,将其上调至最高耐受剂量水平(80mgBID或160mgBID),然后随机分配至缬沙坦或沙库巴曲/缬沙坦。心肌耗氧量,心脏工作的能量效率,在55例患者(ARNI组-27例患者,治疗前和治疗6周(稳定剂量)后,使用超声心动图和11C-乙酸PET对心脏和全身血流动力学进行了定量,年龄63±10岁,EF29.2±10.4%,和缬沙坦唯一对照组-28例,年龄64±8岁,EF29.0±7.3%,所有的NS。)在两个治疗组中,心脏工作的能量效率保持不变。然而,舒张压(-4.5mmHg;p=0.026)和收缩压(-9.8mmHg;p=0.0007),心肌灌注(-0.054mL/g/min;p=0.045),与对照组相比,ARNI组的LV机械功(-296;p=0.038)显着降低。尽管与导入期相比,ARNI组的心肌耗氧量降低(-5.4%),而对照组(0.5%)保持不变,治疗组之间差异不显著(p=0.088)。
结论:我们发现,在HFrEF患者中,ARNI组和缬沙坦组之间心脏工作的能量效率没有差异。然而,在HF患者中,ARNI似乎对缬沙坦具有血液动力学和心脏机械作用。(EudraCT2017-002113-64)本文受版权保护。保留所有权利。