TY - JOUR
T1 - Patients with pulmonary arterial hypertension with and without cardiovascular risk factors
T2 - Results from the AMBITION trial
AU - for the AMBITION Study Group
AU - McLaughlin, Vallerie V.
AU - Vachiery, Jean Luc
AU - Oudiz, Ronald J.
AU - Rosenkranz, Stephan
AU - Galiè, Nazzareno
AU - Barberà, Joan A.
AU - Frost, Adaani E.
AU - Ghofrani, Hossein Ardeschir
AU - Peacock, Andrew J.
AU - Simonneau, Gérald
AU - Rubin, Lewis J.
AU - Blair, Christiana
AU - Langley, Jonathan
AU - Hoeper, Marius M.
N1 - Funding Information:
GlaxoSmithKline makes available anonymized individual participant data and associated documents from interventional clinical studies which evaluate medicines, upon approval of proposals submitted to www.clinicalstudydatarequest.com. To access data for other types of GlaxoSmithKline-sponsored research, for study documents without patient-level data, and for clinical studies not listed, please submit an inquiry via the website. ClinicalTrials.gov identifier: NCT01178073. Dr McLaughlin: grants and personal fees from Actelion, Bayer, Gilead, Ikaria, and United Therapeutics; grants from Novartis; personal fees from SteadyMed and Akros. Dr Vachiery: grants to Dr Vachiery's institution from Actelion and GlaxoSmithKline; speaker fees to Dr Vachiery's institution from Actelion, Bayer, GlaxoSmithKline, Pfizer, and Sonnivie; advisory board honoraria to Dr Vachiery's institution from Actelion and Merck. Dr Oudiz: honoraria for lectures and/or consultancy from Actelion, Gilead, Lung Biotechnology, Reata, and United Therapeutics; honoraria for participation on data safety monitoring committee from Medtronic; grants from Actelion, Arena, Gilead, Lung Biotechnology, Reata, and United Therapeutics. Dr Rosenkranz: honoraria for lectures and/or consultancy from Actelion, Bayer, BMS, GSK, MSD, Novartis, Pfizer, and United Therapeutics; grants from Actelion, Bayer, Novartis, and United Therapeutics. Dr Gali?: grants and personal fees from Actelion, Bayer, GlaxoSmithKline, and Pfizer. Dr Barber?: personal fees from Actelion, Bayer, and GlaxoSmithKline; grants from Actelion, Bayer, GlaxoSmithKline, and Pfizer. Dr Frost: funds for the conduct of the study from Baylor College of Medicine; honoraria and travel/lodging expense for being a member of the Steering Committee; grants from Actelion, Bayer, Gilead, and United Therapeutics; personal fees from Actelion, Bayer, Gilead, Ikaria, and United Therapeutics; non-financial support from Bayer and Novartis. Dr Ghofrani: grants from Actelion, Bayer, Novartis, and Pfizer; board membership and consultancy for Actelion, Bayer, GlaxoSmithKline, Merck, Novartis, and Pfizer; payment for lectures from Actelion, Bayer, Novartis, and Pfizer. Dr Peacock: grants and personal fees from Actelion, Bayer, Gilead, and GlaxoSmithKline; personal fees from United Therapeutics. Dr Simonneau: grants and personal fees from Actelion, Bayer, Gilead, and GlaxoSmithKline. Dr. Rubin: consulting fees from Actelion, Arena, Gilead, and Karos. Ms. Blair: employee of Gilead; stock options in Gilead. Mr. Langley: former employee of GlaxoSmithKline. Dr. Hoeper: personal fees from Actelion, Bayer, Gilead, GlaxoSmithKline, Merck, and Pfizer. Statistical support was provided by Julia H.N. Harris, MA, of GlaxoSmithKline (Uxbridge, United Kingdom). Editorial support was provided by Michael S. McNamara, MS, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company, with funding from Gilead Sciences, Inc and GlaxoSmithKline. The sponsors (Gilead Sciences, Inc in the USA; GlaxoSmithKline in Canada, Europe, Japan, and Australia) funded the study and, along with the authors, drafted the protocol. Monitoring and data collection were performed or overseen by the sponsor. Data were collected in electronic case report forms, which were retained by the sponsor with copies sent to the investigator.
Funding Information:
Statistical support was provided by Julia H.N. Harris, MA, of GlaxoSmithKline (Uxbridge, United Kingdom). Editorial support was provided by Michael S. McNamara, MS, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company, with funding from Gilead Sciences, Inc and GlaxoSmithKline.
Publisher Copyright:
© 2019 International Society for Heart and Lung Transplantation
PY - 2019/12
Y1 - 2019/12
N2 - BACKGROUND: The purpose of this study was to compare patients with pulmonary arterial hypertension enrolled in the AMBITION trial with (excluded from the primary analysis set [ex-primary analysis set]) and without (primary analysis set) multiple risk factors for left ventricular diastolic dysfunction. METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to once-daily ambrisentan and tadalafil combination therapy, ambrisentan monotherapy, or tadalafil monotherapy. The primary end point was time from randomization to first adjudicated clinical failure event. RESULTS: Primary analysis set patients (n = 500), compared with ex-primary analysis set patients (n = 105), were younger (mean, 54.4 vs 62.1 years) with greater baseline 6-minute walk distance (median, 363.7 vs 330.5 meters) and fewer comorbidities (e.g., hypertension and diabetes). Treatment effects of initial combination therapy vs pooled monotherapy were directionally the same for both populations, albeit of a lower magnitude for ex-primary analysis set patients. Initial combination therapy reduced the risk of clinical failure compared with pooled monotherapy in primary analysis set patients (hazard ratio, 0.50; 95% confidence interval, 0.35–0.72), whereas the effect was less clear in ex-primary analysis set patients (hazard ratio, 0.70; 95% confidence interval, 0.35–1.37). Overall, primary analysis set patients had fewer clinical failure events (25% vs 33%), higher rates of satisfactory clinical response (34% vs 24%), and lower rates of permanent study drug withdrawal due to adverse events (16% vs 31%) than ex-primary analysis set patients. CONCLUSIONS: Efficacy of initial combination therapy vs pooled monotherapy was directionally similar for primary analysis set and ex-primary analysis set patients. However, ex-primary analysis set patients (with multiple risk factors for left ventricular diastolic dysfunction) experienced higher rates of clinical failure events and the response to combination therapy vs monotherapy was attenuated. Tolerability was better in primary analysis set than ex-primary analysis set patients.
AB - BACKGROUND: The purpose of this study was to compare patients with pulmonary arterial hypertension enrolled in the AMBITION trial with (excluded from the primary analysis set [ex-primary analysis set]) and without (primary analysis set) multiple risk factors for left ventricular diastolic dysfunction. METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to once-daily ambrisentan and tadalafil combination therapy, ambrisentan monotherapy, or tadalafil monotherapy. The primary end point was time from randomization to first adjudicated clinical failure event. RESULTS: Primary analysis set patients (n = 500), compared with ex-primary analysis set patients (n = 105), were younger (mean, 54.4 vs 62.1 years) with greater baseline 6-minute walk distance (median, 363.7 vs 330.5 meters) and fewer comorbidities (e.g., hypertension and diabetes). Treatment effects of initial combination therapy vs pooled monotherapy were directionally the same for both populations, albeit of a lower magnitude for ex-primary analysis set patients. Initial combination therapy reduced the risk of clinical failure compared with pooled monotherapy in primary analysis set patients (hazard ratio, 0.50; 95% confidence interval, 0.35–0.72), whereas the effect was less clear in ex-primary analysis set patients (hazard ratio, 0.70; 95% confidence interval, 0.35–1.37). Overall, primary analysis set patients had fewer clinical failure events (25% vs 33%), higher rates of satisfactory clinical response (34% vs 24%), and lower rates of permanent study drug withdrawal due to adverse events (16% vs 31%) than ex-primary analysis set patients. CONCLUSIONS: Efficacy of initial combination therapy vs pooled monotherapy was directionally similar for primary analysis set and ex-primary analysis set patients. However, ex-primary analysis set patients (with multiple risk factors for left ventricular diastolic dysfunction) experienced higher rates of clinical failure events and the response to combination therapy vs monotherapy was attenuated. Tolerability was better in primary analysis set than ex-primary analysis set patients.
KW - ambrisentan
KW - combination therapy
KW - pulmonary arterial hypertension
KW - randomized controlled trial
KW - tadalafil
UR - http://www.scopus.com/inward/record.url?scp=85073827858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073827858&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2019.09.010
DO - 10.1016/j.healun.2019.09.010
M3 - Article
C2 - 31648845
AN - SCOPUS:85073827858
VL - 38
SP - 1286
EP - 1295
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
SN - 1053-2498
IS - 12
ER -