Ambrisentan and Tadalafil Combination Therapy Appropriate for CTD-PAH

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; ClinicalTrials.gov 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

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.”

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

References

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.