PAH Treatment Pathways 

How 3 pathways could be the key to feeling better

The key to staying on top of your disease is to find a treatment plan that helps you reduce your symptoms and feel better, make progress toward your goals, and improve your long-term prognosis. There are 3 treatment pathways, and if you are taking only 1 or 2 medications to treat your PAH but are still having symptoms, there may be more you can do to feel better.  

Quote: We talked about my treatment options, because I still love to do things like tai chi.

The PAH Pathways

Dr. Lana Melendres-Groves describes the 3 pathways for treating PAH and how they each can affect your symptoms.

Click to expand transcript

In this video, we’ll discuss the 3 treatment pathways in PAH. PAH treatment centers around 3 substances that are produced by the inner layer of the smaller blood vessels in the lungs. The 3 important substances are nitric oxide, endothelin, and prostacyclin. When you have the right amount of each of these 3 substances, they keep the blood vessels healthy. This allows red blood cells to flow freely through the lungs and transport oxygen to the rest of the body.

Nitric oxide, 1 of the 3 important substances, helps ensure blood vessels stay open and that blood is flowing properly. People with PAH have too little nitric oxide. Endothelin is the second important substance related to PAH. Endothelin causes blood vessels to contract. However, people with PAH have too much endothelin. Prostacyclin is the third important substance in PAH. It helps blood vessels stay open, helps prevent clotting, and slows down the rapid cell growth, which can prevent vessels from becoming too thick. People with PAH have too little prostacyclin. When all 3 of these substances are at proper levels, blood flow is normal, but too much endothelin and not enough prostacyclin or nitric oxide disrupts the natural balance and results in the blood vessels thickening and narrowing.

Connecting the pathways to your lungs

PAH is a chronic disease, but it can be treated with several medications. To understand how PAH is treated, it’s important to know what medications are available and why they might be needed.

Remember that PAH involves the narrowing of the blood vessels in your lungs. Why does this happen?

An imbalance of 3 natural substances

Small blood vessels in your lungs produce 3 natural substances: nitric oxide, endothelin, and prostacyclin.

Having the right amount of each of these 3 natural substances helps keep your blood vessels healthy. The right balance enables red blood cells to flow freely through the lungs and carry oxygen to the rest of the body.

When you have PAH, 1 or more of the 3 substances become out of balance. PAH medications work to impact that imbalance.

Currently, there is no test available to determine which of the 3 substances needs to be adjusted. Because patients with PAH generally respond better when more than 1 pathway is treated, it’s suspected that many patients have more than 1 pathway out of balance.

 

PAH medications help restore balance among the 3 substances

Each PAH medication works to impact only 1 of the 3 pathways: the nitric oxide pathway, the endothelin pathway, or the prostacyclin pathway. Each medication helps bring one substance back into balance.

Nitric oxide pathway

Class of Medicines

Phosphodiesterase-5 inhibitor (PDE-5i)

Soluble guanylate cyclase stimulator (sGCS)

Available form

Icon for oral pde5 medicine for PAH

Endothelin pathway

Class of Medicines

Endothelin receptor antagonist (ERA)

Available form

Icon for oral ERA medicine for PAH

Prostacyclin pathway

Class of Medicines

Prostacyclin-class therapy (prostacyclin = PCY)

Available forms

Icons depicting delivery methods of prostacyclin-class therapies

Looking for more good days?

PAH treatment guidelines recommend that most patients should have more than 1 pathway treated. Research shows that for many people with PAH, taking more than 1 medication to treat more than 1 pathway can delay disease progression. 

An analysis of 17 studies involving more than 4,000 patients found that patients who took only 1 PAH medication were at a higher risk of their PAH worsening. So, if you’re taking 2 or 3 medications to treat your PAH, it’s more likely your PAH will remain the same or improve.

The analysis also found that taking at least 2 PAH medications helped

  • Improve 6-minute walk distance
  • Improve Functional Class
  • Reduce risk for PAH-related hospital admissions

Adding a PAH medication could lead to additional symptom control and allow you to spend more time feeling like yourself. If you are still experiencing symptoms, talk with your healthcare provider about your treatment options. There may be more you can do.

Treating PAH

Dr. Lana Melendres-Groves explains how PAH treatments work and what therapies are recommended by the PAH treatment guidelines.

Click to expand transcript

Researchers have taken the knowledge of how these substances work and created medicines that mimic what the healthy body does naturally. Each medication class treats 1 of 3 pathways: the nitric oxide pathway, the endothelin pathway, or the prostacyclin pathway (screen shows three pathways). Medications that treat the nitric oxide pathway help keep the blood vessels open and blood flowing freely. These medications are available in pill form. Medications that treat the endothelin pathway block the extra endothelin in patients with PAH to help stop the blood vessels from contracting. These are also available in pill form. Medications that treat the prostacyclin pathway help keep the blood vessels open and prevent clotting. These medications are available in pill, inhaled, and infused forms. Medications in each of these 3 treatment classes have been proven to improve factors such as 6-minute walk distances, Functional Class, and reduce symptoms.

Some patients ask if there’s a test to see which treatment pathway would be best for them, but no such test exists at this time. However, for many patients, treating PAH with only 1 of the 3 drug therapies is not enough. Using treatments from the different pathways is recommended by experts for patients who are just starting treatment as well as for those who are already being treated with 1 of the 3 classes. Current guidelines suggest that treating PAH using medicines from 3 classes may be appropriate for some patients. Another strategy that your healthcare provider may use to address your treatment goals is to add additional medications before your PAH gets worse. When looking at the long-term data from a number of studies, an analysis found that patients who delayed adding another PAH medicine didn’t improve their 6-minute walk test as much as those who started the medicine 12 to 16 weeks earlier. That’s why now is the time to speak to your doctor about your treatment plan.

PAH knowledge is PAH power 

How many natural substances are important in the treatment of PAH?

True or false? Currently, there is no test available to determine whether 1, 2, or all 3 substances need to be adjusted.

Take the next step and find out what you can do to fight PAH

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What is prostacyclin-class therapy?  

Prostacyclin-class medications have been used in the treatment of PAH for more than 20 years. Research shows that prostacyclin-class medicine can help people with PAH in several ways.

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