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.  

Image of woman with PAH exercising
Transcript

Hello again. I’m Dr. Lana Melendres-Groves, a pulmonary arterial hypertension specialist and director of the Pulmonary Hypertension Program at the University of New Mexico. I have been treating pulmonary diseases for over 12 years with a specialization in PAH for over 9 years. My clinic has treated over 5,000 patients and I currently oversee 250 PAH patients on PAH-specific medicines. If you haven’t seen the PAH Basics and PAH Treatment Goals videos, it’s better to watch those first. 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.

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. 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.

It is important for you to be proactive in managing your PAH and to work with your doctor to make sure your treatment plan will help you reach your treatment goals. Consider asking the following questions: How can I reduce my symptoms? Is my 6-minute walk distance improving? What can I do to improve my Functional Class? Is my treatment plan helping me reduce my risk for PAH progression? How can I be more proactive in managing PAH? And make sure to discuss any other questions you have with your doctor. I’ll leave you with one last tip before we finish. Be proactive and do all you can to help manage PAH by finding a doctor who has experience treating many PAH patients and by asking your PAH doctor if there’s more you can do now before your PAH progresses. Thank you for watching PAH Treatment Options. Feel free to go back and review the PAH Initiative videos at any time.

Treating PAH 

Dr. Lana Melendres-Groves describes the 3 pathways for treating PAH and the ways that treatment can help you reduce your symptoms and possibly feel better.

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. 

Adding a PAH medication could lead to additional symptom control, so you feel better, you’re able to do more, and you may have more “good days.” If you are still experiencing symptoms, talk with your healthcare provider about your options. There may be more you can do.

 

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.

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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.