PAH Initiative Events

Journey Through the Evolving PAH Landscape
Lana Melendres-Groves, MD:

Hello, and welcome to the PAH Today National Broadcast Series. My name is Dr. Lana Melendres-Groves, and I'm the medical director for the pulmonary hypertension program at the University of New Mexico, and it is my pleasure to take you through the journey of the evolving PAH landscape. First, let me provide the following disclaimer. This presentation is sponsored by, and made on behalf of United Therapeutics. Healthcare professional speakers are compensated by UT. Now, not all medications are appropriate for all patients. Speak with your healthcare professional to determine the right treatment plan for you. First, let's talk about the PAH treatment landscape. More specifically, I'm going to touch on medications, risk assessment tools and tests, and lifestyle management, and supplemental therapies. For some of you, this may be all brand new, and for others, you may have been part of this progress over the last few decades. Overall, these medication options are there to help smooth the road ahead.

These medications can help provide balance to our patients' bodies. There are four pathways in the body, each producing a different natural substance that keeps the blood vessel in the lungs healthy. We also are aware that most patients with PAH have two or more substances out of balance. This can lead to narrowing of blood vessels, thickening of vessel walls, worsening symptoms, and over time, strain on the heart. Now, you may be asking, "Dr. Melendres, what does that have to do with car tires?" And you're right, maybe it's a stretch, but for me, I often find that when I take complex ideas, and I relate them to something that is more commonplace, it's easier for me to understand. And for me, when I think about a car's four tires, you need the right amount of air pressure in each of them to help the car run smoothly.

It's very similar to our own body. Everything has to be in balance for us to feel good. Each type of medication can help rebalance a substance in the corresponding pathway. Each of our PAH medication classes has its role. You can see the road signs indicating prostacyclin, endothelin, nitric oxide, and activin-signaling. First, I'd like to talk about our longest standing medication class, which is prostacyclin. It was initially approved in 1995, so it's been around a while, where our activin-signaling, it was approved in 2024. It's a new class of medication that was approved to target the activin-signaling pathway. Now you might start to wonder, goodness, there are so many choices, and that's fantastic, but how do we decide? This is where experts have gotten together to establish guidelines recommending which PAH medication classes should typically be used first, and how you might add on as necessary. One of the things that we've found over the many years of progress has been that often it requires not just one medication for PAH, but a combination of medications.

For instance, if we go back to our tires, if we had several tires that were either underinflated or overinflated, we wouldn't just pick one to fix. We would want to have them all fixed, so that we run smoothly. PAH medications work differently, and so by balancing those different substances, often two or more of them for most patients, we find that patient symptoms improve. I want to break down each of the different pathways of medication. We'll start with our prostacyclin pathway. This is a medication that helps restore levels of prostacyclin that are low. People with PAH may not produce enough of this substance, so when we provide back the prostacyclin through the medication, we're helping to open narrowed blood vessels in the lungs, slow down the thickening of those vessel walls, and also prevent blood clotting. Interestingly enough, this is the one pathway that has multiple delivery methods.

For instance, we're able to give this medication as an inhaled medication, and we found actually recently that this is the fastest growing way patients are taking the prostacyclin class of medications, and this is a delivery system that goes directly to the lungs, but we also have pill forms of the medication, as well as patients who need a pump form of the therapy. Frequently, this medication is added to a treatment plan over time. It is combined with other medications, especially if we are finding patients are not meeting the goals that we would like for them. Many of the things that we have seen in our trials, our research has been that this class of medication may help to reduce the pressure in the blood vessels of the lungs. It can help people walk more. We see this when it comes to our six-minute walk test that we have patients perform.

Also, we find that there are fewer symptoms in our patients' daily activities, and long-term helping to slow the progression of PAH. I would love to say that this medication is easily taken, but like almost every medication, there's the potential for side effects, and this class of medication, often we see that patients do develop headaches or gastrointestinal problems such as diarrhea or abdominal pain. It's really important. This is a tried and true therapy that if it's a medication your provider has recommended, to talk to them about how you may able to prevent some of those side effects, so that you're successful in the use of this medication. Now, we're going to move into the endothelin pathway. This is a medication that helps reduce the levels of endothelin. So if we're thinking of our tire, it's a bit overinflated. People with PAH may produce too much endothelin, and when we give the medication to sort of block that substance, what we're trying to do is open those narrowed blood vessels in the lungs, and slow down the thickening in the lungs' blood vessels.

This medication is only available in pill form. They're often used as a full treatment plan, either in combination with other medications, but at times may be used alone. The goal is to get our patients to a low risk status. Moving into the nitric oxide pathway, this is a medication that our patients with PAH don't seem to make enough. It's too low, so that's that underinflated tire. The medication helps to restore that balance. We're thinking about the blood vessels in the lungs, and opening those narrowed blood vessels, slowing down the thickening in the lungs' blood vessels. All right, now we've come to this new one that some of you may have been reading up and well aware of, and others I'd like to talk about this activin-signaling pathway. This medication helps to treat an imbalance. This imbalance is in the substance called activin and TGF-beta.

I don't expect you to know anything about those, except to say that they're out of balance in our PAH patients' body. It was approved in 2024, and this medication pathway helps to balance the overgrowth of blood vessels in the lungs, and helps the blood vessels function more effectively. Interestingly enough, this is given in a different way. This is an injectable form of medication. So as you can see, there's a lot of options for our patients when it comes to medications, and the overall goal is to get our patients to a low risk status, so their outcomes and their symptoms are better. All right, let's move into the second portion for today, which is, why do experts recommend two or even more PAH medications for many of our patients? Well, treating those multiple pathways may help to fix the substance imbalances. Again, thinking about our tires, instead of just fixing one that may be low, we may take air out of another that is overinflated.

Unfortunately, we're not like our cars where we can do a test and tell which one of those tires is the one causing us problems. We currently do not have any tests available that can specifically tell us which of the pathways is out of balance. Being able to treat multiple pathways that might help individual patients, knowing that they are each different and may need something slightly different, may provide better results in the long term. So, the other aspect that becomes kind of challenging is, at what point should we be adding more therapy or changing therapy, and what might the clues be in terms of those imbalances? Well, this is where symptoms and risk status come into play. It's extremely important that you find a PAH specialist who has experience using all of the different types of PAH medications. This will allow you every opportunity to be on the therapy that may work best for you.

According to our research, when we treat two or more pathways, then patients tend to have a reduction in their symptoms, they increase their ability to do their daily activities. We call this functional class, or FC, in order to know, how are they doing on the day-to-day? We also see that the patients' walk distances improve, that's our six-minute walk test, and overall improving their risk status. Unfortunately, we see that many patients only receive one PAH therapy, that those additional therapies have not been provided. And so, our goal is just like what you're here to do today, advocate for yourself, educate yourself, so that you can ask those questions of your provider. All right, so which medication do you add? Well, that depends on your unique PAH, but I think it's important to ask those questions, as I mentioned. Ask them to yourself first, so that you can then discuss it with your specialist.

What are your current PAH symptoms? Are they getting better? Have they stayed unchanged? Or maybe you're not feeling as good as you used to. Is that the time to change a medication or add a medication? Next, what are your goals? Discussing that with your family and your support system, and then discussing that with your specialist is extremely important. Being able to understand what ideally should you expect, and how do you get there. Next, do you know your PAH risk status? Often, we don't discuss it enough with our patients. This is extremely important for me, so that my patients can come in and understand why we do the tests that we do, and if we haven't gotten them to a low risk status, we should be discussing what might be available to get them there. For instance, maybe that's an addition of a prostacyclin class medication or changing in their therapies.

Another question you might consider asking are, do you have other conditions besides your PAH? Often, we overlook other concerns of our patients, because we're so focused on the blood vessels, and those medications, but in reality, we need to take the entire person as a whole in order to know what might be best for them. All right, moving into this final chapter for today, what road are you going to find yourself on during your journey through the changing PAH landscape? Each of you will be different, and so I try to never compare one patient to another. I take a patient for who they are, where they started, and where we're going to get to. This is where customizing your treatment plan is tremendously important. Three of the things to think about are, when to add or change medications, what other supplemental therapies might be beneficial, and are there lifestyle changes that might benefit you as well?

There's always more that potentially can be done, and those discussions should be had with your PAH specialist. Let's talk a little bit about adding supplemental therapies. Your treatment plan isn't just PAH medications. More recently, the experts went back and realized that the guidelines should be updated, that we should be talking more about giving guidance for supplemental oxygen depending on what someone's oxygen level is and what their symptoms are. There's also been a lot of data that says getting patients into cardiopulmonary rehab and supervised exercise can long-term benefit them. So, depending on what your status is and what your symptoms are, those may be areas that you can talk to your provider about, but that ongoing evaluation is essential. This is where often people get lost in the mix of life. I really suggest to make sure you're routinely seeing your PAH therapy person, all right? Those may be physicians, those may be advanced providers, whoever they are, talking to them, setting up the schedule of what your road looks like is important, getting those risk assessments, re-evaluating with echocardiograms, and other tests.

The recommendations are that at least every three to six months you should be seen by your PAH specialist, and that when you are being seen, you should have received an echocardiogram to reevaluate how the right side of your heart is doing, as well as potentially getting other routine tests that would be recommended by your PAH specialist. All right, so this is where you get to take charge of your PAH treatment journey. Find a PAH specialist, or if you have one, fantastic. PAH is a rare disease. Doctors who specialize specifically in PAH are well-qualified to understand everything that you need, not just necessarily your PAH, and those specific medications, but the overall person who has this disease. You need to equip yourself for that journey ahead.

Keep finding new ways to learn about PAH, and its treatments. Pay attention to your risk status. Connect with other PAH travelers through support systems or online resources. Make sure you stay empowered in your healthcare decisions. Keep going, I know some days are harder than others, but it's important to keep learning, to keep asking questions, so that you're able to unlock that hope and provide yourself with the change that you need. You can see a QR code for a specialist. Please utilize that if you don't feel that you have someone who is in your corner. And again, some of those suggested questions to ask at your next appointment. First, you may ask, what tests do you use to evaluate and monitor my PAH? Or how frequently should we have follow-up appointments to monitor my condition and adjust my treatment plan if it's necessary? What criteria will you use to determine my treatment plan, including medications, and supplemental therapies?

One of the other questions that I would indicate that you should ask, and whether they are affiliated with an accredited PAH center that specializes in PAH treatment and research may not be something that you can find in your local community, but that doesn't mean that there aren't providers in that community who are going to be able to support you along this journey, but I would say the accredited centers do allow for an expansive evaluation, as well as a multidisciplinary approach to your treatments. Other questions that you might ask are, are there additional specialists I should see to optimize my care, such as rheumatologists or cardiologists? And how do I know when it's the right time to contact you with questions or concerns? It's always the right time. For me, if my patients have questions or concerns, I would hope that my staff and I are available to answer them.

So, feel free between those appointment times to reach out if there are questions that you need answers to. And now, that brings us to some of our key takeaways. First, make those visits with your specialist count by knowing how the PAH landscape is changing, knowing about the different kinds of medications matters more now than ever. Ask them about therapies, tools, and measures that you might be able to use to get to your goal. Second, keep asking if you could make changes to achieve low risk. If you aren't at low risk, should you be adding or changing a medication? And if you aren't tracking toward your goals, ask about the potential of using different kinds of medications together.

Third, take charge of your PAH treatment. As we've mentioned, it's a roadmap. Be sure to see your PAH specialist regularly. If your PAH treatment plan is a roadmap, make sure you're using it to get to where you want to go. You are your most important champion, and please, join us at our next PAH Today National Broadcast. We will be discussing the four essential elements of PAH care. You can secure a spot to join us at the QR code or by visiting pahtoday.net.

Let me just thank you for joining us. It's a pleasure always to be with you. Feel free to connect with us on social media or join the initiative for PAH and get knowledge and inspiration delivered right to your inbox. Thank you all, bye.