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Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction

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PARAGON-HF Investigators and Committees. / Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. I: The New England journal of medicine. 2019 ; Bind 381, Nr. 17. s. 1609-1620.

Bibtex

@article{03c990ae0fff40bebae37aa0f7d86bec,
title = "Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction",
abstract = "BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45{\%} or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed.RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95{\%} confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5{\%} in the sacubitril-valsartan group and 8.9{\%} in the valsartan group (hazard ratio, 0.95; 95{\%} CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95{\%} CI, 0.72 to 1.00). NYHA class improved in 15.0{\%} of the patients in the sacubitril-valsartan group and in 12.6{\%} of those in the valsartan group (odds ratio, 1.45; 95{\%} CI, 1.13 to 1.86); renal function worsened in 1.4{\%} and 2.7{\%}, respectively (hazard ratio, 0.50; 95{\%} CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95{\%} CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45{\%} or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).",
keywords = "Aged, Aminobutyrates/administration & dosage, Angioedema/chemically induced, Angiotensin Receptor Antagonists/administration & dosage, Cardiovascular Diseases/mortality, Double-Blind Method, Female, Follow-Up Studies, Heart Failure/drug therapy, Hospitalization/statistics & numerical data, Humans, Hypotension/chemically induced, Male, Middle Aged, Neprilysin/antagonists & inhibitors, Quality of Life, Sex Factors, Single-Blind Method, Stroke Volume, Tetrazoles/administration & dosage, Valsartan/administration & dosage",
author = "Solomon, {Scott D} and McMurray, {John J V} and Anand, {Inder S} and Junbo Ge and Lam, {Carolyn S P} and Maggioni, {Aldo P} and Felipe Martinez and Milton Packer and Pfeffer, {Marc A} and Burkert Pieske and Redfield, {Margaret M} and Rouleau, {Jean L} and {van Veldhuisen}, {Dirk J} and Faiez Zannad and Zile, {Michael R} and Desai, {Akshay S} and Brian Claggett and Jhund, {Pardeep S} and Boytsov, {Sergey A} and Josep Comin-Colet and John Cleland and Hans-Dirk D{\"u}ngen and Eva Goncalvesova and Tzvetana Katova and {Kerr Saraiva}, {Jose F} and Małgorzata Lelonek and Bela Merkely and Michele Senni and Shah, {Sanjiv J} and Jingmin Zhou and Rizkala, {Adel R} and Jianjian Gong and Shi, {Victor C} and Lefkowitz, {Martin P} and {PARAGON-HF Investigators and Committees}",
note = "Copyright {\circledC} 2019 Massachusetts Medical Society.",
year = "2019",
month = "10",
day = "24",
doi = "10.1056/NEJMoa1908655",
language = "English",
volume = "381",
pages = "1609--1620",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "17",

}

RIS

TY - JOUR

T1 - Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction

AU - Solomon, Scott D

AU - McMurray, John J V

AU - Anand, Inder S

AU - Ge, Junbo

AU - Lam, Carolyn S P

AU - Maggioni, Aldo P

AU - Martinez, Felipe

AU - Packer, Milton

AU - Pfeffer, Marc A

AU - Pieske, Burkert

AU - Redfield, Margaret M

AU - Rouleau, Jean L

AU - van Veldhuisen, Dirk J

AU - Zannad, Faiez

AU - Zile, Michael R

AU - Desai, Akshay S

AU - Claggett, Brian

AU - Jhund, Pardeep S

AU - Boytsov, Sergey A

AU - Comin-Colet, Josep

AU - Cleland, John

AU - Düngen, Hans-Dirk

AU - Goncalvesova, Eva

AU - Katova, Tzvetana

AU - Kerr Saraiva, Jose F

AU - Lelonek, Małgorzata

AU - Merkely, Bela

AU - Senni, Michele

AU - Shah, Sanjiv J

AU - Zhou, Jingmin

AU - Rizkala, Adel R

AU - Gong, Jianjian

AU - Shi, Victor C

AU - Lefkowitz, Martin P

AU - PARAGON-HF Investigators and Committees

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2019/10/24

Y1 - 2019/10/24

N2 - BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed.RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).

AB - BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed.RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women.CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).

KW - Aged

KW - Aminobutyrates/administration & dosage

KW - Angioedema/chemically induced

KW - Angiotensin Receptor Antagonists/administration & dosage

KW - Cardiovascular Diseases/mortality

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Heart Failure/drug therapy

KW - Hospitalization/statistics & numerical data

KW - Humans

KW - Hypotension/chemically induced

KW - Male

KW - Middle Aged

KW - Neprilysin/antagonists & inhibitors

KW - Quality of Life

KW - Sex Factors

KW - Single-Blind Method

KW - Stroke Volume

KW - Tetrazoles/administration & dosage

KW - Valsartan/administration & dosage

U2 - 10.1056/NEJMoa1908655

DO - 10.1056/NEJMoa1908655

M3 - Journal article

VL - 381

SP - 1609

EP - 1620

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 17

ER -

ID: 59425855