Objectives To evaluate initial combination therapy with ambrisentan plus tadalafil (COMB) compared with monotherapy of either agent (MONO), and the utility of baseline characteristics and risk stratification in predicting outcomes, in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and the systemic sclerosis (SSc)–pulmonary arterial hypertension (PAH) subpopulation.
Methods This post hoc analysis of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) study included patients with CTD-PAH from the modified intention-to-treat population. Time to clinical failure (TtCF) was assessed by baseline characteristics, treatment assignment and risk group (low, intermediate and high) at baseline and week 16. TtCF was compared between groups using Kaplan-Meier curves and Cox proportional hazards regression modelling.
Results The analysis included 216 patients (COMB, n=117; MONO, n=99). The risk of clinical failure was lower with COMB versus MONO (risk reduction: CTD-PAH 51.7%, SSc-PAH 53.7%), particularly in patients with haemodynamic parameters characteristic of typical PAH without features of left heart disease and/or restrictive lung disease at baseline. The risk of clinical failure was lower with COMB versus MONO in the baseline low-risk group (HR not calculated due to no events in COMB), baseline intermediate-risk group (HR 0.519, 95% CI 0.297 to 0.905) and in the week 16 low-risk group (HR 0.069, 95% CI 0.009 to 0.548).
Conclusions The benefit of COMB over MONO was demonstrated in patients with CTD-PAH, particularly in those with typical PAH haemodynamic characteristics at baseline. COMB is appropriate for patients categorised as low risk and intermediate risk at baseline and low risk at follow-up.
Trial registration number NCT01178073.
- arterial hypertension
- outcomes research
- systemic sclerosis
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Handling editor Josef S Smolen
Correction notice This article has been corrected since it published Online First. In table 1, the unit of PVR has been corrected and number of FC III in SSC/Mono amended.
Contributors All listed authors contributed substantially to the planning and implementation of this research. All authors revised the manuscript critically for important intellectual content, approved the final version for publication and agreed to be listed as authors.
Funding This study was funded by GlaxoSmithKline (study number 112565) and Gilead Sciences, Inc.
Competing interests MK has received personal fees from GSK, Bayer and Nippon Shinyaku, and research grants and personal fees from Actelion and Pfizer. CB is an employee and shareholder at Gilead Sciences. JL is a former employee and shareholder of GSK. TT is an employee at GSK. JGC has received research grants and personal fees from Actelion and GSK, and personal fees from Bayer, Endotronix, Pfizer and United Therapeutics.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Anonymised individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.
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