TY - JOUR T1 - Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1219 LP - 1227 DO - 10.1136/annrheumdis-2016-210236 VL - 76 IS - 7 AU - John Gerry Coghlan AU - Nazzareno Galiè AU - Joan Albert Barberà AU - Adaani E Frost AU - Hossein-Ardeschir Ghofrani AU - Marius M Hoeper AU - Masataka Kuwana AU - Vallerie V McLaughlin AU - Andrew J Peacock AU - Gérald Simonneau AU - Jean-Luc Vachiéry AU - Christiana Blair AU - Hunter Gillies AU - Karen L Miller AU - Julia H N Harris AU - Jonathan Langley AU - Lewis J Rubin AU - for the AMBITION investigators Y1 - 2017/07/01 UR - http://ard.bmj.com/content/76/7/1219.abstract N2 - Background Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH.Objective To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial.Methods This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response).Results In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups.Conclusions This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy.Trial registration number NCT01178073, post results. ER -