1. Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study: Effect Modification by Left Ventricular Ejection Fraction and Sex
- Author
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Gary F. Mitchell, Scott D. Solomon, Amil M. Shah, Brian L. Claggett, James C. Fang, Joseph Izzo, Cheryl A. Abbas, Akshay S. Desai, Melvin Martinez-Castrillon, Coral Gables, Jorge Beato, Vipul Shah, Leonard Pianko, Manuel Bouza, Mohsin Alhaddad, Amir Kashani, Gregory Sampognaro, Lloyd Stahl, John Lehman, Steve Lebhar, Mark Napoli, Aurelio Torres Consuegra, Humberto Gonzalez, Ramon Lloret, Mehrdad Ariani, Masoud Azizad, Anil Shah, David Henderson, John Covalesky, David Brabham, Majed Chane, Eulogio Sanchez, Ramses Vega, Anthony Clay, John McClure, Felix Sogade, Luis Ortiz-Munoz, Todd Lewis, Argentina Gonzalez Zequeira, Rakesh Shah, Norman Lepor, Marisela Gonzalez, Raymond Tidman, Jeffrey Berman, David Lorenz, Michele Nanna, Trevor Greene, Edward Portnay, Marc Bernstein, Guillermo Somodevilla, Robert Grodman, Mary Gaffney, Hyeun Park, Isaac Dor, Shamaila Aslam, Richard Jackson, Guido Perez, Luis Martinez, Glenn Gandelman, Johnny Dy, Abraham Salacata, Rafik Abadier, John Steuter, Sadeem Mahmood, Harold Betton, Kishor Vora, Jose Tallaj, Debra Weinstein, Hassana Alhosaini, John Everett, Michael Rosenberg, Stephanie Dunlap, Olakunle Akinboboy, Jasjit Walia, Yuly Lyandres, Barry Harris, Wael Abo-Auda, Zebediah Stearns, Navid Kazemi, Arden Bradley, Lucien Megna, Jeff Taylor, Anthony Innasimuthu, L. Douglas Waggoner, Denzil Moraes, Sandeep Jani, Nicolas Chronos, Nikhil Joshi, Michael Radin, Amer Suleman, Paul Grena, Subodh Agrawal, and Mark Holmberg
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Male ,medicine.medical_specialty ,Angiotensin-Converting Enzyme Inhibitors ,Effect Modifier, Epidemiologic ,Angiotensin Receptor Antagonists ,Sex Factors ,Vascular Stiffness ,Enalapril ,Internal medicine ,medicine ,Humans ,In patient ,Hemodynamic effects ,Aged ,Heart Failure ,Ejection fraction ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,Hemodynamics ,Stroke Volume ,Middle Aged ,medicine.disease ,Drug Combinations ,Blood pressure ,Treatment Outcome ,Heart failure ,Cardiology ,Valsartan ,Female ,Cardiology and Cardiovascular Medicine ,business ,Effect modification ,Sacubitril, Valsartan ,medicine.drug - Abstract
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 P 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 LVEFc 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.
- Published
- 2021