Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension
Abstract Background Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in m...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-019-1180-1 |
| _version_ | 1818324658078875648 |
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| author | R. James White Anton Vonk-Noordegraaf Stephan Rosenkranz Ronald J. Oudiz Vallerie V. McLaughlin Marius M. Hoeper Ekkehard Grünig Hossein-Ardeschir Ghofrani Murali M. Chakinala Joan A. Barberà Christiana Blair Jonathan Langley Adaani E. Frost |
| author_facet | R. James White Anton Vonk-Noordegraaf Stephan Rosenkranz Ronald J. Oudiz Vallerie V. McLaughlin Marius M. Hoeper Ekkehard Grünig Hossein-Ardeschir Ghofrani Murali M. Chakinala Joan A. Barberà Christiana Blair Jonathan Langley Adaani E. Frost |
| author_sort | R. James White |
| collection | DOAJ |
| description | Abstract Background Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants. Methods AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, ambrisentan 10 mg plus placebo, or tadalafil 40 mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline. Results This analysis included 500 participants in the previously defined primary analysis set (n = 155 FC II, n = 345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups. Conclusions Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe. Funded by Gilead Sciences, Inc. and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073. |
| first_indexed | 2024-12-13T11:32:05Z |
| format | Article |
| id | doaj.art-f44fd922b4584cd3b84761a83b713dd5 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-13T11:32:05Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-f44fd922b4584cd3b84761a83b713dd52022-12-21T23:47:54ZengBMCRespiratory Research1465-993X2019-09-0120111010.1186/s12931-019-1180-1Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertensionR. James White0Anton Vonk-Noordegraaf1Stephan Rosenkranz2Ronald J. Oudiz3Vallerie V. McLaughlin4Marius M. Hoeper5Ekkehard Grünig6Hossein-Ardeschir Ghofrani7Murali M. Chakinala8Joan A. Barberà9Christiana Blair10Jonathan Langley11Adaani E. Frost12Division of Pulmonary & Critical Care Medicine, University of Rochester Medical CenterDepartment of Pulmonary Medicine and Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Cardiology and Cologne Cardiovascular Research Center (CCRC), Heart Center at the University of CologneDivision of Cardiology, LA Biomedical Research Institute at Harbor-UCLA Medical CenterDivision of Cardiovascular Medicine, University of MichiganDepartment of Respiratory Medicine, Hannover Medical School, German Center for Lung Research (DZL)Centre for pulmonary hypertension, German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University HospitalGerman Center for Lung Research (DZL), Kerckhoff Clinic, Department of Pulmonology, Universities of Giessen and Marburg Lung Center (UGMLC)Division of Pulmonary & Critical Care Medicine, Washington UniversityDepartment of Pulmonary Medicine, Hospital Clínic-IDIBAPS, University of BarcelonaGilead SciencesGlaxo Smith KlineHouston Methodist Hospital, Institute for Academic MedicineAbstract Background Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants. Methods AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, ambrisentan 10 mg plus placebo, or tadalafil 40 mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline. Results This analysis included 500 participants in the previously defined primary analysis set (n = 155 FC II, n = 345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups. Conclusions Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe. Funded by Gilead Sciences, Inc. and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.http://link.springer.com/article/10.1186/s12931-019-1180-1Pulmonary hypertensionResearch-clinicalCombination therapy |
| spellingShingle | R. James White Anton Vonk-Noordegraaf Stephan Rosenkranz Ronald J. Oudiz Vallerie V. McLaughlin Marius M. Hoeper Ekkehard Grünig Hossein-Ardeschir Ghofrani Murali M. Chakinala Joan A. Barberà Christiana Blair Jonathan Langley Adaani E. Frost Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension Respiratory Research Pulmonary hypertension Research-clinical Combination therapy |
| title | Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| title_full | Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| title_fullStr | Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| title_full_unstemmed | Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| title_short | Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| title_sort | clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension |
| topic | Pulmonary hypertension Research-clinical Combination therapy |
| url | http://link.springer.com/article/10.1186/s12931-019-1180-1 |
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