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Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study

MAESTRO Study Investigators, Gatzoulis, M. A., Landzberg, M. J., Beghetti, M., Berger, R. M., Efficace, M., Gesang, S., He, J., Papadakis, K., Pulido, T. & Galie, N., 2-Jan-2019, In : Circulation. 139, 1, p. 51-63 13 p.

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APA

MAESTRO Study Investigators, Gatzoulis, M. A., Landzberg, M. J., Beghetti, M., Berger, R. M., Efficace, M., ... Galie, N. (2019). Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study. Circulation, 139(1), 51-63. https://doi.org/10.1161/CIRCULATIONAHA.118.033575

Author

MAESTRO Study Investigators ; Gatzoulis, Michael A. ; Landzberg, Michael J. ; Beghetti, Maurice ; Berger, Rolf M. ; Efficace, Michela ; Gesang, Sophie ; He, Jian'guo ; Papadakis, Kelly ; Pulido, Tomas ; Galie, Nazzareno. / Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study. In: Circulation. 2019 ; Vol. 139, No. 1. pp. 51-63.

Harvard

MAESTRO Study Investigators, Gatzoulis, MA, Landzberg, MJ, Beghetti, M, Berger, RM, Efficace, M, Gesang, S, He, J, Papadakis, K, Pulido, T & Galie, N 2019, 'Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study' Circulation, vol. 139, no. 1, pp. 51-63. https://doi.org/10.1161/CIRCULATIONAHA.118.033575

Standard

Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study. / MAESTRO Study Investigators; Gatzoulis, Michael A.; Landzberg, Michael J.; Beghetti, Maurice; Berger, Rolf M.; Efficace, Michela; Gesang, Sophie; He, Jian'guo; Papadakis, Kelly; Pulido, Tomas; Galie, Nazzareno.

In: Circulation, Vol. 139, No. 1, 02.01.2019, p. 51-63.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

MAESTRO Study Investigators, Gatzoulis MA, Landzberg MJ, Beghetti M, Berger RM, Efficace M et al. Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study. Circulation. 2019 Jan 2;139(1):51-63. https://doi.org/10.1161/CIRCULATIONAHA.118.033575


BibTeX

@article{e9ba09bca8f8460688f0c16b86c61015,
title = "Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study",
abstract = "BACKGROUND: Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.METHODS: Patients with Eisenmenger syndrome aged >= 12 years and in World Health Organization functional class II-III were randomized 1: 1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.RESULTS: Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60{\%} of patients were in World Health Organization functional class II and 27{\%} were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95{\%} confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8{\%} and 14.3{\%} of patients in the macitentan and placebo groups (odds ratio, 0.53; 95{\%} CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95{\%} CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95{\%} CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5{\%}) and upper respiratory tract infection (9.6 versus 6.3{\%}); a hemoglobin decrease from baseline of >= 2 g/dL occurred in 36.0{\%} versus 8.9{\%} of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).CONCLUSIONS: Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.",
keywords = "congenital heart disease, Down syndrome, Eisenmenger syndrome, endothelin receptor antagonist, macitentan, pulmonary arterial hypertension, PULMONARY-ARTERIAL-HYPERTENSION, CONGENITAL HEART-DISEASE, DOUBLE-BLIND, EXERCISE CAPACITY, BOSENTAN THERAPY, INHALED ILOPROST, TREPROSTINIL, SILDENAFIL, SURVIVAL, EFFICACY",
author = "{MAESTRO Study Investigators} and Gatzoulis, {Michael A.} and Landzberg, {Michael J.} and Maurice Beghetti and Berger, {Rolf M.} and Michela Efficace and Sophie Gesang and Jian'guo He and Kelly Papadakis and Tomas Pulido and Nazzareno Galie",
year = "2019",
month = "1",
day = "2",
doi = "10.1161/CIRCULATIONAHA.118.033575",
language = "English",
volume = "139",
pages = "51--63",
journal = "Circulation",
issn = "0009-7322",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "1",

}

RIS

TY - JOUR

T1 - Evaluation of Macitentan in Patients With Eisenmenger Syndrome Results From the Randomized, Controlled MAESTRO Study

AU - MAESTRO Study Investigators

AU - Gatzoulis, Michael A.

AU - Landzberg, Michael J.

AU - Beghetti, Maurice

AU - Berger, Rolf M.

AU - Efficace, Michela

AU - Gesang, Sophie

AU - He, Jian'guo

AU - Papadakis, Kelly

AU - Pulido, Tomas

AU - Galie, Nazzareno

PY - 2019/1/2

Y1 - 2019/1/2

N2 - BACKGROUND: Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.METHODS: Patients with Eisenmenger syndrome aged >= 12 years and in World Health Organization functional class II-III were randomized 1: 1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.RESULTS: Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of >= 2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).CONCLUSIONS: Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.

AB - BACKGROUND: Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.METHODS: Patients with Eisenmenger syndrome aged >= 12 years and in World Health Organization functional class II-III were randomized 1: 1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.RESULTS: Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of >= 2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).CONCLUSIONS: Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.

KW - congenital heart disease

KW - Down syndrome

KW - Eisenmenger syndrome

KW - endothelin receptor antagonist

KW - macitentan

KW - pulmonary arterial hypertension

KW - PULMONARY-ARTERIAL-HYPERTENSION

KW - CONGENITAL HEART-DISEASE

KW - DOUBLE-BLIND

KW - EXERCISE CAPACITY

KW - BOSENTAN THERAPY

KW - INHALED ILOPROST

KW - TREPROSTINIL

KW - SILDENAFIL

KW - SURVIVAL

KW - EFFICACY

U2 - 10.1161/CIRCULATIONAHA.118.033575

DO - 10.1161/CIRCULATIONAHA.118.033575

M3 - Article

VL - 139

SP - 51

EP - 63

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 1

ER -

ID: 73907429