美国波士顿布列根和妇女医院Scott D. Solomon与合作者探讨了与依那普利相比，Sacubitril-缬沙坦治疗射血分数降低型心力衰竭（HFrEF）能否改善主动脉硬化和心脏重塑。相关论文2019年9月2日在线发表于《美国医学会杂志》。

2016年8月17日至2018年6月28日，研究组对美国85个地区的464名心力衰竭和射血分数不超过40%的参与者进行了一项随机、双盲的临床试验，这些参与者的平均年龄为67.3岁，女性占23.5%。后续工作于2019年1月26日完成，共有427名参与者完成试验。

治疗第12周时，Sacubitril-缬沙坦组的主动脉特性阻抗有所降低，依那普利组则小幅升高。然而，与依那普利组相比，Sacubitril-缬沙坦组的左房容积、左室舒张末期容积指数（LVEDVI）、左室收缩末期容积指数（LVESVI）和二尖瓣e/e′比值均明显降低。Sacubitril-缬沙坦组中包括低血压在内的不良反应发生率为1.7%，依那普利组为3.9%，无统计学差异。

研究人员总结说，与依那普利相比，Sacubitril-缬沙坦治疗HFrEF并没有显著减少主动脉硬化。

据悉，与依那普利相比，Sacubitril-缬沙坦治疗HFrEF可降低心血管死亡率和心力衰竭住院率。这些益处可能与血流动力学和心脏重塑的影响有关。

附：英文原文

Title: Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction  A Randomized Clinical Trial

Author: Akshay S. Desai, MD, MPH1; Scott D. Solomon, MD1; Amil M. Shah, MD1; Brian L. Claggett, PhD1; James C. Fang, MD2; Joseph Izzo, MD3; Kevin McCague, MA4; Cheryl A. Abbas, PharmD4; Ricardo Rocha, MD4; Gary F. Mitchell, MD5; for the EVALUATE-HF Investigators

Issue&Volume: September 2, 2019

Abstract：

Importance  Compared with enalapril, sacubitril-valsartan reduces cardiovascular mortality and heart failure hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). These benefits may be related to effects on hemodynamics and cardiac remodeling.

Objective  To determine whether treatment of HFrEF with sacubitril-valsartan improves central aortic stiffness and cardiac remodeling compared with enalapril.

Design, Setting, and Participants  Randomized, double-blind clinical trial of 464 participants with heart failure and ejection fraction of 40% or less enrolled across 85 US sites between August 17, 2016, and June 28, 2018. Follow-up was completed on January 26, 2019.

Interventions  Randomization (1:1) to sacubitril-valsartan (n = 231; target dosage, 97/103 mg twice daily) vs enalapril (n = 233; target dosage, 10 mg twice daily) for 12 weeks.

Main Outcomes and Measures  The primary outcome was change from baseline to week 12 in aortic characteristic impedance (Zc), a measure of central aortic stiffness. Prespecified secondary outcomes included change from baseline to week 12 in N-terminal pro–B-type natriuretic peptide, ejection fraction, global longitudinal strain, mitral annular relaxation velocity, mitral E/e′ ratio, left ventricular end-systolic and end-diastolic volume indexes (LVESVI and LVEDVI), left atrial volume index, and ventricular-vascular coupling ratio.

Results  Of 464 validly randomized participants (mean age, 67.3 [SD, 9.1] years; 23.5% women), 427 completed the study. At 12 weeks, Zc decreased from 223.8 to 218.9 dyne × s/cm5 in the sacubitril-valsartan group and increased from 213.2 to 214.4 dyne × s/cm5 in the enalapril group (treatment difference, −2.2 [95% CI, −17.6 to 13.2] dyne × s/cm5; P = .78). Of 9 prespecified secondary end points, no significant between-group difference in change from baseline was seen in 4, including left ventricular ejection fraction (34%-36% with sacubitril-valsartan vs 33 to 35% with enalapril; treatment difference, 0.6% [95% CI, −0.4% to 1.7%]; P = .24). However, greater reductions from baseline were seen with sacubitril-valsartan than with enalapril in all others, including left atrial volume (from 30.4 mL/m2 to 28.2 mL/m2 vs from 29.8 mL/m2 to 30.5 mL/m2; treatment difference, −2.8 mL/m2 [95% CI, −4.0 to −1.6 mL/m2]; P < .001), LVEDVI (from 75.1 mL/m2 to 70.3 mL/m2 vs from 79.1 mL/m2 to 75.6 mL/m2; treatment difference, −2.0 mL/m2 [95% CI, −3.7 to 0.3 mL/m2]; P = .02), LVESVI (from 50.8 mL/m2 to 46.3 mL/m2 vs from 54.1 to 50.6 mL/m2; treatment difference, −1.6 mL/m2 [95% CI, −3.1 to −0.03 mL/m2]; P = .045), and mitral E/e′ ratio (from 13.8 to 12.3 vs from 13.4 to 13.8; treatment difference, −1.8 [95% CI, −2.8 to −0.8]; P = .001). Rates of adverse events including hypotension (1.7% vs 3.9%) were similar in both groups.

Conclusions and Relevance  Treatment of HFrEF with sacubitril-valsartan, compared with enalapril, did not significantly reduce central aortic stiffness. The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in HFrEF.