Treatment With Oral or Inhaled Treprostinil in Patients With Pulmonary Arterial Hypertension and Cardiovascular Comorbidities.

BACKGROUND

An increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood.

RESEARCH QUESTION

Do cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil?

STUDY DESIGN AND METHODS

All patients from phase 3 studies Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (TRIUMPH) (N = 235) and Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy (FREEDOM-EV) (N  =  690) were included in this post hoc analysis and were classified as having 0, ≥ 1, or ≥ 2 cardiovascular comorbidities of interest based on patient medical history. The mean difference in 6-minute walk distance and N-terminal pro-brain natriuretic peptide from baseline to week 12 was assessed for TRIUMPH, and the risk and incidence of clinical worsening was assessed for patients in FREEDOM-EV. Adverse events were summarized for each comorbidity grouping for TRIUMPH and FREEDOM-EV.

RESULTS

In TRIUMPH, there were 79, 156, and 88 patients with 0, ≥ 1, and ≥ 2 comorbidities, respectively. Patients on inhaled treprostinil had improvements in 6-minute walk distance, with numerically similar improvements for comorbidity subgroups (0: 26 m, P = .020; ≥ 1: 22 m, P = .006; ≥ 2: 21.6 m, P = .043). Significant reductions in N-terminal pro-brain natriuretic peptide were also seen in all subgroups. In FREEDOM-EV, there were 375, 315, and 166 patients with 0, ≥ 1, and ≥ 2 comorbidities, respectively. Regardless of comorbidities, patients on oral treprostinil had a significantly reduced risk of clinical worsening compared with placebo (0: 36% reduction, P = .034; ≥ 1: 41% reduction, P = .014; ≥ 2: 45% reduction, P = .026). In TRIUMPH and FREEDOM-EV, adverse event profiles were typical for this class of medication regardless of the number of comorbidities. A sensitivity analysis using a subset of comorbidities confirmed the findings of our primary analysis.

INTERPRETATION

This post hoc analysis suggests that patients with PAH and cardiovascular comorbidities can benefit from combination therapy with inhaled or oral treprostinil.