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Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

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Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. / Galiè, Nazzareno; Barberà, Joan A; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiery, Jean-Luc; Grünig, Ekkehard; Oudiz, Ronald J; Vonk-Noordegraaf, Anton; White, R James; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J; AMBITION Investigators.

In: NEW ENGL J MED, Vol. 373, No. 9, 27.08.2015, p. 834-44.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Galiè, N, Barberà, JA, Frost, AE, Ghofrani, H-A, Hoeper, MM, McLaughlin, VV, Peacock, AJ, Simonneau, G, Vachiery, J-L, Grünig, E, Oudiz, RJ, Vonk-Noordegraaf, A, White, RJ, Blair, C, Gillies, H, Miller, KL, Harris, JHN, Langley, J, Rubin, LJ & AMBITION Investigators 2015, 'Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension', NEW ENGL J MED, vol. 373, no. 9, pp. 834-44. https://doi.org/10.1056/NEJMoa1413687

APA

Galiè, N., Barberà, J. A., Frost, A. E., Ghofrani, H-A., Hoeper, M. M., McLaughlin, V. V., Peacock, A. J., Simonneau, G., Vachiery, J-L., Grünig, E., Oudiz, R. J., Vonk-Noordegraaf, A., White, R. J., Blair, C., Gillies, H., Miller, K. L., Harris, J. H. N., Langley, J., Rubin, L. J., & AMBITION Investigators (2015). Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. NEW ENGL J MED, 373(9), 834-44. https://doi.org/10.1056/NEJMoa1413687

Vancouver

Galiè N, Barberà JA, Frost AE, Ghofrani H-A, Hoeper MM, McLaughlin VV et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. NEW ENGL J MED. 2015 Aug 27;373(9):834-44. https://doi.org/10.1056/NEJMoa1413687

Bibtex

@article{d7b198e11dab4437ade5064b69709fa4,
title = "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension",
abstract = "BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).",
keywords = "Adult, Aged, Carbolines, Disease Progression, Double-Blind Method, Drug Therapy, Combination, Female, Hospitalization, Humans, Hypertension, Pulmonary, Kaplan-Meier Estimate, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Phenylpropionates, Pyridazines, Risk Factors",
author = "Nazzareno Gali{\`e} and Barber{\`a}, {Joan A} and Frost, {Adaani E} and Hossein-Ardeschir Ghofrani and Hoeper, {Marius M} and McLaughlin, {Vallerie V} and Peacock, {Andrew J} and G{\'e}rald Simonneau and Jean-Luc Vachiery and Ekkehard Gr{\"u}nig and Oudiz, {Ronald J} and Anton Vonk-Noordegraaf and White, {R James} and Christiana Blair and Hunter Gillies and Miller, {Karen L} and Harris, {Julia H N} and Jonathan Langley and Rubin, {Lewis J} and {AMBITION Investigators} and Hans Klose",
year = "2015",
month = aug,
day = "27",
doi = "10.1056/NEJMoa1413687",
language = "English",
volume = "373",
pages = "834--44",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "9",

}

RIS

TY - JOUR

T1 - Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

AU - Galiè, Nazzareno

AU - Barberà, Joan A

AU - Frost, Adaani E

AU - Ghofrani, Hossein-Ardeschir

AU - Hoeper, Marius M

AU - McLaughlin, Vallerie V

AU - Peacock, Andrew J

AU - Simonneau, Gérald

AU - Vachiery, Jean-Luc

AU - Grünig, Ekkehard

AU - Oudiz, Ronald J

AU - Vonk-Noordegraaf, Anton

AU - White, R James

AU - Blair, Christiana

AU - Gillies, Hunter

AU - Miller, Karen L

AU - Harris, Julia H N

AU - Langley, Jonathan

AU - Rubin, Lewis J

AU - AMBITION Investigators

AU - Klose, Hans

PY - 2015/8/27

Y1 - 2015/8/27

N2 - BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

AB - BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

KW - Adult

KW - Aged

KW - Carbolines

KW - Disease Progression

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Hospitalization

KW - Humans

KW - Hypertension, Pulmonary

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Natriuretic Peptide, Brain

KW - Peptide Fragments

KW - Phenylpropionates

KW - Pyridazines

KW - Risk Factors

U2 - 10.1056/NEJMoa1413687

DO - 10.1056/NEJMoa1413687

M3 - SCORING: Journal article

C2 - 26308684

VL - 373

SP - 834

EP - 844

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 9

ER -