Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study
Authors: Mitchell Gary F. , Solomon Scott D. , Shah Amil M. , Claggett Brian L. , Fang James C. , Izzo Joseph , Abbas Cheryl A. , Desai Akshay S. , Martinez-Castrillon Melvin , Gables Coral , Beato Jorge , Shah Vipul , Pianko Leonard , Bouza Manuel , Alhaddad Mohsin , Kashani Amir , Sampognaro Gregory , Stahl Lloyd , Lehman John , Lebhar Steve , Napoli Mark , Torres Consuegra Aurelio , Gonzalez Humberto , Lloret Ramon , Ariani Mehrdad , Azizad Masoud , Shah Anil , Henderson David , Covalesky John , Brabham David , Chane Majed , Sanchez Eulogio , Vega Ramses , Clay Anthony , McClure John , Sogade Felix , Ortiz-Munoz Luis , Lewis Todd , Zequeira Argentina Gonzalez , Shah Rakesh , Lepor Norman , Gonzalez Marisela , Tidman Raymond , Berman Jeffrey , Lorenz David , Nanna Michele , Greene Trevor , Portnay Edward , Bernstein Marc , Somodevilla Guillermo , Grodman Robert , Gaffney Mary , Park Hyeun , Dor Isaac , Aslam Shamaila , Jackson Richard , Perez Guido , Martinez Luis , Gandelman Glenn , Dy Johnny , Salacata Abraham , Abadier Rafik , Steuter John , Mahmood Sadeem , Betton Harold , Vora Kishor , Tallaj Jose , Weinstein Debra , Alhosaini Hassana , Everett John , Rosenberg Michael , Dunlap Stephanie , Akinboboy Olakunle , Walia Jasjit , Lyandres Yuly , Harris Barry , Abo-Auda Wael , Stearns Zebediah , Kazemi Navid , Bradley Arden , Megna Lucien , Taylor Jeff , Innasimuthu Anthony , Waggoner L. Douglas , Moraes Denzil , Jani Sandeep , Chronos Nicolas , Joshi Nikhil , Radin Michael , Suleman Amer , Grena Paul , Agrawal Subodh , Holmberg Mark 
Published: March 2021

Background:
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.

Methods:

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
c
) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12.

Results:

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,
P
<0.001) and pulse pressure (−3.0±0.8 mm Hg,
P
<0.001). Postdose reductions in Z
c
were greater in the sacubitril-valsartan group (−16±6 dyne×second/cm
5
,
P
=0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction
P
=0.036). With LVEF<0.40, postdose reductions in Z
c
were greater in the sacubitril-valsartan group (trough, −3±8 dyne×second/cm
5
versus post-dose, −17±8 dyne×second/cm
5
; interaction
P
=0.024) with no sex difference (treatment×sex interaction,
P
=0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z
c
in women (women, −80±21 dyne×second/cm
5
versus men, −20±13 dyne×second/cm
5
; interaction
P
=0.019).

Conclusions:

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
c
. In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z
c
in women with LVEF≥0.40.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT02874794.