Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

Abstract

BackgroundPatients 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.ObjectiveTo 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.MethodsThis 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).ResultsIn 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.ConclusionsThis 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.

Two‐dimensional knowledge‐based volumetric reconstruction of the right ventricle documents short‐term improvement in pulmonary hypertension

“…26 NT-proBNP level is higher at diagnosis despite similar hemodynamics 27 indicating a poorer tolerance of PH than other forms of PAH. 30 Secondly, in our population, RV volumes were significantly more dilated at baseline in comparison with above mentioned studies. This would be supported by recent evidence that CTD-associated and systemic sclerosis-associated PAH patients benefit from aggressive PAH-targeted treatment.…”

Predictors of Favorable Responses to Immunosuppressive Treatment in Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

“…However, it is worth considering the fact that, in the present study, only a few patients received upfront combination therapy, which has been confirmed to be more efficacious than initial monotherapy in patients with PAH-CTD. 35 This finding does not necessarily mean that the concomitant use of pulmonary vasodilators is useless for patients with SLE/MCTD/primary SS-PAH. Nevertheless, patients who are likely to respond to the first-line IS treatment, such as those simultaneously diagnosed as having PAH and CTD or those with a mild hemodynamic impairment, could be treated initially with IS treatment alone.…”

Pulmonary hypertension in systemic sclerosis: different phenotypes

“…Moreover, SSc-PAH patients are most often less responsive than patients with idiopathic PAH and have a worse prognosis, although they present with milder haemodynamic impairment [2][3][4][5]. However, recent studies have suggested that where aggressive therapy is used, a similar reduction in event rate is achievable in SSc and idiopathic PAH populations [6,7]. The reasons why SSc-PAH patients could exhibit different behaviour than patients with other forms of PAH is still a matter of debate.…”