Combination therapy is appropriate for patients with typical pulmonary arterial hypertension (PAH) categorized as low and intermediate risk at baseline, while high-risk patients could possibly be considered for more advanced therapy, according to study results published in the Annals of the Rheumatic Diseases.1

Connective tissue disease-associated PAH (CTD-PAH) is the second most common etiology of PAH and has the most severe disease characteristics and the highest mortality of all PAH subgroups.1 The Ambrisentan and Tadalafil in Patients with PAH study (AMBITION; Identifier: NCT01178073) demonstrated that patients with CTD-PAH benefited from initial combination therapy with ambrisentan plus tadalafil compared with either agent alone when patients with risk factors for left heart disease were excluded.2

Researchers conducted a post hoc subgroup analysis of the AMBITION modified intention-to-treat CTD-PAH population to assess the relationship between baseline characteristics and outcome and evaluated the utility of an abbreviated, 3-parameter noninvasive risk stratification score in predicting outcomes in patients with CTD-PAH.1

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This analysis included 216 patients (combination therapy, n=117; monotherapy, n=99), and they found that the risk for clinical failure was lower with combination therapy vs monotherapy, specifically 51.7% lower in the CTD-PAH population (hazard ratio [HR], 0.48; 95% CI, 0.28%-0.81%) and 53.7% in the systemic sclerosis-PAH population (HR, 0.46; 95% CI, 0.24%-0.89%). The risk for clinical failure was lower with combination therapy vs monotherapy in the baseline low-risk group, baseline intermediate-risk group, and in the week 16 low-risk group.

“In patients with CTD-PAH, the risk of clinical failure was lower with combination therapy versus monotherapy, particularly in those with baseline hemodynamic parameters characteristic of typical PAH, without features of left heart disease and/or restrictive lung disease,”1 the investigators wrote. “A simplified risk stratification score at baseline may help inform disease management in patients with CTD-PAH, but further studies with larger patient populations are required.”

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Disclosure: This clinical trial was supported by GlaxoSmithKline and Gilead Sciences, Inc. Please see the original reference for a full list of authors’ disclosures.


1. Kuwana M, Blair C, Takahashi T, Langley J, Coghlan JG. Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis [published online March 11, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216274

2. Galiè N, Barberà JA, Frost AE, et al; for the AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834-844.