Prostacyclin-Class Therapy

Prostacyclin-class therapies have unique characteristics

Prostacyclins were the first class of therapy approved for PAH, and their use in managing PAH has evolved substantially over time. Historically, prostacyclin-class therapies have been used primarily in patients with more severe disease or as a rescue-type therapy.1 However, current evidence supports the use of prostacyclin-class therapies throughout PAH management in appropriate patients, and prostacyclin-class therapies can be combined with other classes of PAH medications as part of an individualized management plan. The availability of expanded treatment delivery options has also enabled prostacyclin-class therapies to be more conveniently integrated into patients’ daily lives.2

Prostacyclin-class medications are available in 3 different forms

Prostacyclin-class therapies are available in oral and inhaled formulations, as well as through parenteral delivery.2 These varying routes of administration provide the flexibility to match your patient’s disease status and lifestyle.

Icon of oral pillOral prostacyclins

are easy to take by mouth and require little to no training3

Icon of lungsInhaled prostacyclins

are delivered directly to the small pulmonary vessels affected by PAH. Patients breathe the prostacyclin medication directly into the lungs when using inhaled formulations4

Icon of infusionParenteral prostacyclins

provide continuous medication delivery to the patient and require a pump—for which smaller options have been developed—and either a central venous line or a subcutaneous catheter5

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Prostacyclin-class medications mimic the diverse functions of naturally occurring PCY

PAH is associated with progressive vascular remodeling resulting in narrowed, thickened pulmonary blood vessels.6 Although the exact mechanisms of PAH are unknown, most PAH medications induce vasodilation to counteract the narrowed blood vessels, each via a different pathway. Prostacyclin-class medications differ in that they not only induce vasodilation but also have significant antithrombotic and antiproliferative properties.7 In addition, some data suggest prostacyclin-class medications may contribute to anti-inflammatory effects.8

AEs associated with prostacyclin-class therapies include headache, diarrhea, flu-like symptoms, jaw pain, nausea, muscle pain, and flushing.9 Additional AEs may be specific to the drug and route of administration.3-5

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Prostacyclins can improve prognostic measures of risk

The demonstrated benefits of prostacyclin-class therapies include:
  • Improved PAH symptoms10,11
  • Improved prognostic measures of risk
    • Functional Class10,12
    • 6MWD10,12
    • BNP/NT-proBNP12,13
    • Hemodynamics10,11
  • Delayed disease progression3,14

Prostacyclin Pathway

Endogenous prostacyclin is important to normal lung function. PAH may be characterized by abnormally low levels of prostacyclin. Learn about complications in the lungs caused by inadequate levels of prostacyclin.

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The Prostacyclin Pathway

PAH may be characterized by abnormally low levels of prostacyclin, or PGI2, a naturally occurring metabolite of arachidonic acid that is endogenous to the body.

Prostacyclin carries out several important actions to help maintain proper heart and lung function. Prostacyclin deficiency has been linked with increased pulmonary arterial pressure, disease severity, and disease progression.

Complications in the lungs caused by inadequate levels of prostacyclin include constriction of the small pulmonary arteries, hypertrophy and proliferation of vascular smooth muscle cells, and heightened risk of blood clotting.

Additionally, data suggests insufficient prostacyclin levels may be associated with pulmonary arterial inflammation.

Therapies which aim to compensate for missing prostacyclin, known as prostacyclin-class medications, are currently formulated for multiple routes of administration including inhaled, oral, subcutaneous, and IV.

Prostacyclin-class therapies may be considered as part of a combination therapy approach in PAH

More pathways may mean better results

Combination therapy regimens—including those that contain a prostacyclin-class medication—are a mainstay of PAH management, as patients on combination therapy have shown improved outcomes vs patients on monotherapy.2,12,15,16

The AMBITION study was pivotal in establishing the benefits of early combination therapy in patients with PAH. Nonetheless, despite being on dual oral therapy under optimal conditions, only 39% of patients achieved a satisfactory clinical response.16 In another study of patients initiated on dual combination therapy, most patients did not achieve low-risk status within 6 months.17

Another approach is to consider a combination regimen that includes a prostacyclin-class therapy. In combination studies with a prostacyclin-class therapy, improvements were seen in common PAH endpoints such as 6MWD, NT-proBNP, and delay in disease progression.10-14

Graphic depicting baseline and 6-month follow up results for low, intermediate, and high risk with a callout detailing that 65% of patients were not at low-risk at the 6-month follow up.

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6MWD=6-minute walk distance; AE=adverse event; BNP=brain natriuretic peptide; ESC/ERS=European Society of Cardiology/European Respiratory Society; NT-proBNP=N-terminal pro-brain natriuretic peptide; PAH=pulmonary arterial hypertension.References: 1. Burger CD, et al. Am J Manag Care. 2016;22(1 suppl):S3-S15. 2. Humbert M, et al. Eur Heart J. 2022;43(38):3618-3731. 3. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2021. 4. TYVASO [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2022. 5. Remodulin [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2021. 6. Champion HC, et al. Circulation. 2009;120(11):992-1007. 7. Hassoun PM. N Engl J Med. 2021;385(25):2361-2376. 8. Pugliese SC, Bull TM. Integr Blood Press Control. 2016;9:1-7. 9. Farber HW, Gin-Sing W. Eur Respir Rev. 2016;25(142):418-430. 10. Barst RJ, et al. N Engl J Med. 1996;334(5):296-301. 11. Oudiz RJ, et al. Chest. 2004;126(2):420-427. 12. White RJ, et al. Am J Respir Crit Care Med. 2020;201(6):707-717. 13. McLaughlin VV, et al. J Am Coll Cardiol. 2010;55(18):1915-1922. 14. Uptravi [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; 2022. 15. Galiè N, et al. Eur Heart J. 2016;37(1):67-119. 16. Galiè N, et al. N Engl J Med. 2015;373(9):834-844. 17. Badagliacca R, et al. Am J Respir Crit Care Med. 2021;203(4):484-492.