← Back to Mar 2014

Oral Prostacyclins: Our Newest Medication for Pulmonary Arterial Hypertension

links image

Veronica Franco, MD
ISHLT PH Council Links Liaison
Assistant Professor of Clinical Medicine
Ohio State University
Columbus, Ohio, USA

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease that leads to right sided heart failure. Thirty years ago, adults diagnosed with PAH could expect to live less than 3 years, and the therapies limited to nonselective vasodilators (calcium channel blockers) and warfarin. Today, the physician has a number of choices and continues to expand with three new medications approved in 2013.

Prostacyclins, the first approved therapy, are still utilized and remain one of the main classes of PAH therapy. Currently, continuous SQ / IV formulations are typically utilized in severe PAH and patients with functional class III or IV. There is growing evidence that earlier use may benefit patients with mild to moderate disease [1]. Nevertheless, IV prostacyclins are not consistently used in the most seriously ill patients. Unfortunately they are often started late or not at all with ~ 50% of patients with PAH were not using prostacyclins at the time of their death [2]. In December 2013, the FDA approved an oral treprostinil, (Orenitram) for the treatment of PAH in WHO Group I patients. This approval marks the first time that the FDA has approved an orally administered prostacyclin analogue for PAH.

The FREEDOM-M study [3], evaluated oral treprostinil in newly diagnosed patients not yet treated with PAH specific medications. The study demonstrated that patients receiving treprostinil twice daily improved their median six-minute walk distance (6MWD) by +23 meters [p=0.013] as compared to patients receiving only placebo. The maximum dose was determined by tolerability. Side effects were similar to those of other prostacyclins - headache, nausea, diarrhea, hypotension, inhibition of platelet aggregation and risk of bleeding.

The approval of this medication provides potential significant advantages in the care for patients with PAH:

Yet, several questions remain unanswered regarding the use of oral treprostinil in the treatment of PAH:

Orenitram is a very promising medication for the treatment of PAH. Stay tuned for additional studies evaluating efficacy and tolerability of this medication!

Disclosure Statement: the author reports the following disclosures:


  1. Farber HW, Miller D, Meltzer LA, et al. Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL registry. J HeartLungTransplant 2013;32:1114-1122.
  2. Vachiery JL. Prostacyclins in pulmonary arterial hypertension: the need for earlier therapy. Adv Ther 2011:28;251-269.
  3. Jing ZA, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized controlled trial. Circulation 2013;127:624-633.
  4. Tapson VF, Jing ZA, Xu KF, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelial receptor antagonist or phosphodiesterase type 5 inhibitor therapy (The FREEDOM C2 study). Chest 2013;144; 952-958.
  5. Barst R, McGoon M, McLaughlin VV, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003;41:2119-2125.

Share via:

links image    links image    links image    links image