medwireNews: A post-hoc subgroup analysis of the AMBITION trial suggests that the benefits of ambrisentan and tadalafil combination therapy extend to patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).
John Gerry Coghlan (Royal Free Hospital, London, UK) and colleagues analyzed data from 187 CTD-PAH patients who participated in the AMBITION trial, 118 of whom had systemic sclerosis (SSc)-associated PAH. In the original trial, 500 patients with PAH were randomly assigned to receive initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, or monotherapy with either drug alone.
The researchers found that 19% of 103 CTD-PAH patients treated with combination therapy experienced clinical failure, defined as the first occurrence of death, hospitalization for worsening PAH, disease progression, or unsatisfactory long-term clinical response.
By comparison, 36% of 84 patients in the monotherapy group had a clinical failure event, translating into a 57% risk reduction with combination therapy versus monotherapy.
And among participants with SSc-PAH, 21% of 71 treated with ambrisentan plus tadalafil experienced clinical failure, compared with 40% of 47 in the monotherapy group, corresponding to a 56% risk reduction with combination therapy.
“In the CTD-PAH population, an aggressive approach to treatment with initial combination therapy may improve outcomes and exercise capacity as opposed to treatment with monotherapy,” say the researchers in the Annals of the Rheumatic Diseases.
In both the CTD-PAH and SSc-PAH groups, the researchers observed a greater increase in 6-minute walk distance from baseline to week 24 among patients receiving combination versus monotherapy (42.0 vs 24.3 m and 40.9 vs 12.2 m, respectively).
The most common adverse event was peripheral edema, occurring in 47% of CTD-PAH patients receiving combination therapy, compared with 34% of those receiving ambrisentan alone and 33% receiving tadalafil alone. The corresponding rates in SSc-PAH patients were 45%, 26%, and 33%.
Coghlan et al report that no new safety signal was identified in the post-hoc analysis, and there was “no trend towards an excess” of serious adverse events (SAEs) or AEs leading to treatment discontinuation with combination therapy versus monotherapy.
However, rates of SAEs and AEs leading to treatment discontinuation were higher among trial participants with CTD-PAH compared with idiopathic or heritable PAH, “possibly due to coexisting connective tissue disease,” notes the team.
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