Takeaway
- Oral treprostinil reduces risk of clinical worsening, including death, by 26% in patients with pulmonary arterial hypertension (PAH), according to the FREEDOM-EV trial.
Why this matters
- This is the first trial to assess the clinical outcomes of oral treprostinil therapy for PAH.
- A previous trial found improvement in exercise capacity.
Study design
- Multicentre, randomised, double-blind, placebo-controlled trial (n=690).
- Participants were eligible if using approved oral monotherapy for >30 days prior to randomisation and had a 6-minute walk distance ≥150 m.
- Primary outcome: time to clinical worsening (defined by death, hospitalisation due to worsening PAH, initiation of inhaled or parenteral prostacyclin therapy, disease progression, or unsatisfactory long-term clinical response).
- Funding: United Therapeutics Corporation.
Key results
- The treprostinil group had 26% less clinical worsening (26% vs 36% of placebo group; HR, 0.74; P=.028).
- The treprostinil group had better measures of disease status (including functional class, Borg dyspnoea score, and N-terminal-pro-brain natriuretic peptide) at week ≥24.
- The treprostinil group attained a lower mortality risk profile (at weeks 12-60) despite higher mortality risk at baseline, according to noninvasive risk stratification analysis.
- The most common adverse events were:
- Headache: 69.9% vs 29.7%.
- Diarrhoea: 65.6% vs 19.8%.
- Flushing: 43.6% vs 7.6%.
- Nausea: 37.0% vs 16.9%.
- Vomiting: 32.1% vs 7.6%.
Limitations
- High discontinuation rate, 18.8%.
References
References