Treatment Pathways

Medications are currently approved to treat 3 different pathways

Nitric oxide pathway1,2

PDE-5i therapies and sGCS

  • Induce vasodilation

Available formIcon of oral PAH medication

Prostacyclin pathway1,2

Prostacyclin-class therapies

  • Induce vasodilation
  • Inhibit platelet aggregation
  • Inhibit smooth muscle cell proliferation

Available formIcon of oral, infused, and inhaled PAH medication

Endothelin pathway1,2

ERA therapies

  • Prevent vasoconstrictive and proliferative effects

Available formIcon of oral PAH medication

Each pathway has a different mechanism of action, so each treats PAH in a different way. Patients on combination therapy have shown improved outcomes vs patients on monotherapy.3,4

Treating multiple pathogenic pathways is the current standard of care5

Current treatment guidelines recommend that treating multiple pathogenic pathways is the standard of care for patients. Upon diagnosis of PAH, a multiparameter risk calculation should be conducted to determine your patient’s initial treatment regimen. The guidelines require initial combination treatment based on your patient’s risk status.

  • Low- and intermediate-risk patients should receive ERA + PDE-5i combination therapy at diagnosis. Monotherapy has a residual role in today's treatment guidelines
  • High-risk patients should receive combination therapy that includes an IV prostacyclin therapy

Prostacyclin-class medications have been shown to improve prognostic measures of risk2,6

In the body, naturally produced prostacyclins are potent vasodilators and possess antithrombotic, antiproliferative, and anti-inflammatory properties.7 Prostacyclin-class therapies mimic some of the effects of natural prostacyclin produced by the body. These medications are available in 3 forms: oral, infused, and inhaled.2

The demonstrated benefits of prostacyclin-class therapies include:

  • Improved PAH symptoms6,8
  • Improved prognostic measures of risk
    • Functional Class4,6
    • 6MWD4,6
    • BNP/NT-proBNP4,9
    • Hemodynamics6,8
  • Delayed disease progression10,11

AEs include headache, diarrhea, flu-like symptoms, jaw pain, nausea, muscle pain, and flushing.12 These are not all of the AEs.10 Additional AEs may be specific to the drug and route of administration.

If you make adjustments to your patient’s treatment plan today, you may be able to improve their risk status.2,5

Hear from an expert

“So, there’s wonderful data on prostacyclin-class therapies, about improving symptoms, improving Functional Class, improving hall walk, improving hemodynamics. … These, of course, have to be balanced with the side effects. … But the whole reason that we’re doing this is to improve their symptoms, improve their functional capacity, and improve their outcomes. So you see what I just did there, Ray? I call that the benefits sandwich.”

-Dr. Vallerie McLaughlin
University of Michigan, Ann Arbor

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Dr. Vallerie McLaughlin:

So, there's wonderful data on prostacyclin-class therapies, about improving symptoms, improving Functional Class, improving hall walk, improving hemodynamics. These therapies improve a patient's ability to function, as they set their goal, whether that goal is to be able to take care of their kids or get back to some recreational exercise or be able to go up the stairs and do their job without shortness of breath. These are some of the most potent therapies we have in improving those symptoms.

Now, of course, they delay disease progression. They improve risk profile. And that's one of the reasons why we try to use them in patients who haven't achieved their risk, because we know these are very effective therapies.

These, of course, have to be balanced with the side effects. We know this class of agents have a number of side effects, including headache, diarrhea, jaw pain, nausea, sometimes musculoskeletal symptoms, flushing. And, so, we need to make sure the patients understand that, and that they understand the risks associated with the delivery system. Septicemia, bacteremia, if they're on IV. Cough in inhaled. Sometimes the GI side effects are worse on the orals.

So we need to make sure the patients understand that and understand that we will work with them and have lots of tricks up our sleeve to monitor those side effects and help obviate them.

But the whole reason that we're doing this is to improve their symptoms, improve their functional capacity, and improve their outcomes.

So you see what I just did there, Ray? I call that the benefits sandwich. You tell the patient why you're going to use that therapy, what to expect on the upside, our goals in terms of improving their symptoms and getting them back to what they want, have them set some goals.

Being proactive helps patients reach their goals

Patient goals and behaviors are other factors to consider when making therapy decisions. Although your goal may be for them to achieve low-risk status, the patient’s treatment goal may be to just feel better. Your patient may achieve this goal by adjusting their lifestyle and reducing their activity levels. Although they may feel better, they may not be at low-risk status. Instead of waiting for symptoms to worsen, these patients may benefit from a proactive discussion about modifying their treatment regimen to help improve their symptoms without reducing their activity levels.

Have you asked your patients if they would be willing to adjust their treatment regimen to improve their symptoms and their chance of surviving longer?

When is the right time to initiate a prostacyclin-class therapy?

Review Treatment Guidelines

Hear from an expert

“The goal for patients can be very different than the goal for physicians, and they really should align. A patient’s conception of risk, they may not really be able to fully appreciate what that means for them while they’re still having active symptoms.”

-Dr. Raymond Benza
The Ohio State University

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Dr. Raymond Benza:

The goal for patients can be very different than the goal for physicians, and they really should align. A patient's conception of risk, they may not really be able to fully appreciate what that means for them while they're still having active symptoms.

So it's really important really to drive those symptoms to a state where a patient can really accept the importance of reducing their risk, in terms of their longevity and other technical things, like hospitalization.

Evolving use of prostacyclin-class medications

Today, prostacyclin-class therapies are available in oral, inhaled, or parenteral delivery2 to help fit your patient’s lifestyle and meet their treatment goals.

Historically, prostacyclin-class medications have been underutilized. Initially, prostacyclin-class medications were only available intravenously, and they were reserved for patients with more severe disease.13 In a recent retrospective analysis (2012-2017) of Medicare data from 29,372 patients, only about one-third of patients received a prostacyclin-class therapy before their death.14

Of the 11,993 patients in the retrospective analysis who died14:

72.8%

had a pharmacy claim for a PDE-5i/sGCS

49.2%

had a claim for an ERA

35.9%

had received prostacyclin-class therapy

Now, prostacyclin-class medications are available in 3 formulations,2 and they are approved for use in FC II patients.10,11 Oral prostacyclin-class medications make it easier to treat PAH earlier and more aggressively.10,11

Explore some prostacyclin treatment options from United Therapeutics

Find Treatment Options
6MWD=6-minute walk distance; AE=adverse event; BNP=brain natriuretic peptide; ERA=endothelin receptor antagonist; FC=Functional Class; IV=intravenous; NT-proBNP=N-terminal pro-brain natriuretic peptide; PDE-5i=phosphodiesterase-5 inhibitor; sGCS=soluble guanylate cyclase stimulator.References: 1. Santos-Ribeiro D, et al. Arch Cardiovasc Dis. 2016;109(10):550-561. 2. Galiè N, et al. Eur Heart J. 2016;37(1):67-119. 3. Galiè N, et al. N Engl J Med. 2015;373(9):834-844. 4. White RJ, et al. Respir Crit Care Med. 2020;201(6):707-717. 5. Galiè N, et al. Eur Respir J. 2019;53(1):1801889. 6. Barst RJ, et al. N Engl J Med. 1996;334(5):296-301. 7. Stitham J, et al. Front Pharmacol. 2011;2:24. 8. Oudiz RJ, et al. Chest. 2004;126(2):420-427. 9. McLaughlin, VV, et al. JACC. 2010;55(18):1915-1922.10. Orenitram [package insert]. Research Triangle Park, NC: United Therapeutics Corporation; 2019. 11. Uptravi [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; 2019. 12. Farber HW, Gin-Sing W. Eur Respir Rev. 2016;25(142):418-430. 13. Burger CD, et al. Am J Manag Care. 2016;22(1 suppl):S3-S15. 14. Mathai S, et al. Abstract presented at: American College of Chest Physicians Annual Conference; October 17-20, 2020; Virtual.