Sacubitril-纈沙坦與依那普利對HFrEF患者主動脈硬化的影響
作者：
小柯機器人發布時間：2019/9/4 17:08:30
美國波士頓布列根和婦女醫院Scott D. Solomon與合作者探討了與依那普利相比，Sacubitril-纈沙坦治療射血分數降低型心力衰竭（HFrEF）能否改善主動脈硬化和心臟重塑。相關論文2019年9月2日在線發表於《美國醫學會雜誌》。
2016年8月17日至2018年6月28日，研究組對美國85個地區的464名心力衰竭和射血分數不超過40%的參與者進行了一項隨機、雙盲的臨床試驗，這些參與者的平均年齡為67.3歲，女性佔23.5%。後續工作於2019年1月26日完成，共有427名參與者完成試驗。
治療第12周時，Sacubitril-纈沙坦組的主動脈特性阻抗有所降低，依那普利組則小幅升高。然而，與依那普利組相比，Sacubitril-纈沙坦組的左房容積、左室舒張末期容積指數（LVEDVI）、左室收縮末期容積指數（LVESVI）和二尖瓣e/e′比值均明顯降低。Sacubitril-纈沙坦組中包括低血壓在內的不良反應發生率為1.7%，依那普利組為3.9%，無統計學差異。
研究人員總結說，與依那普利相比，Sacubitril-纈沙坦治療HFrEF並沒有顯著減少主動脈硬化。
據悉，與依那普利相比，Sacubitril-纈沙坦治療HFrEF可降低心血管死亡率和心力衰竭住院率。這些益處可能與血流動力學和心臟重塑的影響有關。
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.