Mitchell Gary F, Solomon Scott D, Shah Amil M, Claggett Brian L, Fang James C, Izzo Joseph, Abbas Cheryl A, Desai Akshay S
Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.).
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (S.D.S., A.M.S., B.L.C., A.S.D.).
Circ Heart Fail. 2021 Mar;14(3):e007891. doi: 10.1161/CIRCHEARTFAILURE.120.007891. Epub 2021 Mar 5.
Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction.
EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12.
In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, -3.0±0.8 mm Hg, <0.001) and pulse pressure (-3.0±0.8 mm Hg, <0.001). Postdose reductions in Z were greater in the sacubitril-valsartan group (-16±6 dyne×second/cm, =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction =0.036). With LVEF<0.40, postdose reductions in Z were greater in the sacubitril-valsartan group (trough, -3±8 dyne×second/cm versus post-dose, -17±8 dyne×second/cm; interaction =0.024) with no sex difference (treatment×sex interaction, =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z in women (women, -80±21 dyne×second/cm versus men, -20±13 dyne×second/cm; interaction =0.019).
In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z. In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02874794.
沙库巴曲缬沙坦治疗可降低射血分数降低的心力衰竭（HF）患者的死亡率和HF事件，并可能减少射血分数保留的HF女性患者的HF住院率。
EVALUATE-HF研究将464例射血分数降低的HF患者（109例女性）随机分为沙库巴曲缬沙坦组或依那普利组，治疗12周。要求在之前12个月内记录的左心室射血分数（LVEF）≤0.40，不过允许核心实验室测定的LVEF>0.40。在基线、第4周和第12周的谷值以及给药后4小时评估主动脉僵硬度（脉压和特性阻抗，Z）。
在根据基线值调整的基线变化模型中，沙库巴曲缬沙坦治疗使平均动脉压总体降低幅度更大（治疗组差异为-3.0±0.8 mmHg，P<0.001），脉压降低幅度更大（-3.0±0.8 mmHg，P<0.001）。沙库巴曲缬沙坦组给药后Z的降低幅度更大（-16±6达因·秒/厘米，P=0.012）。事后分析发现有LVEF效应修正的证据（交互作用P=0.036）。当LVEF<0.40时，沙库巴曲缬沙坦组给药后Z的降低幅度更大（谷值时为-3±8达因·秒/厘米，给药后为-17±8达因·秒/厘米；交互作用P=0.024），且无性别差异（治疗×性别交互作用P=0.3）。当LVEF≥0.40时，沙库巴曲缬沙坦治疗使女性的Z总体降低幅度更大（女性为-80±21达因·秒/厘米，男性为-20±13达因·秒/厘米；交互作用P=0.019）。
在包括第4周和第12周给药前和给药后评估的预先指定分析中，沙库巴曲缬沙坦治疗与给药后主动脉Z的更大降低相关。在事后分析中，沙库巴曲缬沙坦与LVEF≥0.40的女性患者Z的持续降低相关。注册信息：网址：https://www.clinicaltrials.gov；唯一标识符：NCT02874794。
