Endogenous prostacyclin is critical to proper lung function
Naturally occurring prostacyclin plays a crucial role in physiological processes1,2:
- Promotes vasodilation of pulmonary vessels
- Inhibits proliferation of pulmonary vascular smooth muscle cells
- Helps regulate inflammation
- Inhibits platelet aggregation
Patients with pulmonary arterial hypertension (PAH) typically have reduced levels of prostacyclin. Studies of pulmonary arteries compared patients with PAH vs those without PAH and revealed that patients with PAH had lower levels of prostacyclin synthase, indicating lower levels of prostacyclin.3 Reduced levels of prostacyclin are linked to the progressive vascular remodeling associated with PAH that leads to narrowed, thickened pulmonary blood vessels and abnormal hemodynamics, ultimately leading to right heart failure.1,3
Prostacyclin-class therapies supplement naturally occurring prostacyclin
Prostacyclin-class therapies are distinctive in that they address the decrease in prostacyclin that may be found in patients with PAH.4,5 Not only do prostacyclin-class therapies induce vasodilation, but they also exhibit antithrombotic and antiproliferative properties.5
In addition, data show that prostacyclin-class therapies may have anti-inflammatory effects.1,6,7
Explore the critical role of prostacyclin in PAH
Watch this video to learn more about the role of prostacyclin and the impact it may have on your PAH treatment decisions.
[Video title: 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 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.
Why include prostacyclin-class therapy in PAH treatment regimens?
Numerous clinical studies investigated different prostacyclin-class therapies and demonstrated improvements in many prognostic measures of risk, delayed disease progression, and improvement in PVR, an important measure of right heart function.5 These benefits are critical elements of a risk assessment and contribute to a patient’s ability to achieve key treatment goals. As a reminder, today’s treatment goals include improving risk status and near-normalization of the right heart.5,8
Prostacyclin therapies have historically been underutilized, even in patients at high-risk status.9-12 Current expert recommendations encourage using prostacyclin-class therapies as early in the treatment regimen as possible, when indicated, and especially when therapy escalation is required in patients not at low risk.5,13
Prostacyclin-class therapies are available in multiple forms of administration, including nebulizers and small, handheld DPI inhalers, as well as oral pills and SC and IV pump options, which can be used throughout all stages of PAH in combination with other therapies.5,14
Achieving low-risk status is the ultimate goal for patients
Striving for low-risk status is the treatment goal identified for patients in the 2022 ESC/ERS Treatment Guidelines.5 Including a prostacyclin-class therapy in a patient’s treatment regimen has demonstrated benefits that may help patients improve risk parameters, exercise capacity (including 6MWD), and hemodynamics.2,5 Functional improvements include delayed disease progression and improved PAH symptoms, such as shortness of breath and fatigue.5
Learn more about each form of prostacyclin-class therapy
Learn About FormsNear‑normalization of the right heart is another key goal
Since right heart dysfunction is a leading indicator of PAH disease progression, another key treatment goal is near‑normalization of the right‑heart.8,15,16
Prostacyclin-class therapies may help improve hemodynamic parameters that can contribute to right heart health, including5,8,16-20:
- Pulmonary vascular resistance
- Mean pulmonary arterial pressure
- BNP/NT-proBNP
- Cardiac output
- Cardiac index
Prostacyclin side effects
For patients with PAH who use prostacyclin-class therapies, side effects may include headache, diarrhea, jaw pain, nausea, muscle pain, and flushing.5,13,14 These are not all the side effects; additional side effects may be specific to the drug and route of administration.5,14
Prostacyclin-class therapies have a proven safety record―their side effects are well understood, and there are many methods for proactively managing them.14,21 Discussing side effects with patients and collaborating with PH Expert Centers may help your patients manage these effects to stay on treatment.5,14
Expert recommendations across all stages of PAH
Current PAH treatment guidelines supported by the WSPH include recommendations for prostacyclin-class options for patients across risk strata.5,13
Initial therapy
Patients at high risk
- Therapy combination that includes an SC or IV form of prostacyclin therapy
Patients not at high risk but with signs of right heart strain and/or worsening symptoms
- Treatment regimen that includes an infused form of prostacyclin therapy
Follow-up visit
All patients starting PAH therapy should have a follow-up within 3 months to reassess risk status
- For patients not at low risk, adjust therapy
Prostacyclin-class therapy administration options
Prostacyclin-class therapies are now available in multiple administration forms that may help improve patient outcomes.13,14,22
- Inhaled options including nebulizers and small, handheld DPI devices
- Oral options in pill form
- Infused options with various SC and IV pump options
Having a variety of forms lets you:
- Titrate to therapeutic dose efficiently, safely, and effectively22
- Customize a treatment regimen according to a patient’s disease stage and lifestyle5,13,14
- Add an oral or inhaled form for patients who refuse pump IV or SC options13,23
Experience matters: the first PAH therapy approved in 1995 by the US24
Prostacyclin-class therapies have been extensively researched, and current guidelines support their use throughout the management of PAH.5,13 Prostacyclin-class therapies were studied in patients across functional classes (II-IV) as an important part of a patient’s individualized treatment plan.14,25
Convenient, easier-to-use forms of prostacyclin, such as inhaled devices, can be a first step into gaining experience using a prostacyclin-class therapy.25,26 Prostacyclins continue to evolve with updates in pump technology and DPI devices.
At each stage of your patient’s journey, consult with PH Expert Centers to prepare a treatment plan based on the latest management and care recommendations5