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Treatment With Oral or Inhaled Treprostinil in Patients With Pulmonary Arterial Hypertension and Cardiovascular
R James White1, Karim El-Kersh2, Stephan Rosenkranz3
1University of Rochester Medical Center, Rochester, NY.
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.
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