Understanding the Subpopulations of Pulmonary Hypertension - Episode 9
Elucidation of the various treatment strategies used in PH and PAH subpopulations: CTEPH, CTD-PAH, and POPH.
Charles D. Burger, MD: As the physician is making decisions with the patient regarding the best treatment approach, there are several factors that impact those decisions. Most importantly is the severity of the disease, which guides what types of therapies we use in terms of potency, method of delivery, and what we know about them from a science perspective. But subpopulations of Group 1 PAH [pulmonary arterial hypertension] do impact that decision as well. For example, we know that PAH in association with connective tissue disease [CTD] is extremely challenging. The reason the patient has PAH is the systemic connective tissue disease, which of course isn’t going away. That remains forever. There’s ongoing risk to the pulmonary circulation forever because there is an association with the underlying connective tissue disease.
In general, we want to treat those patients as aggressively as possible because of that risk. We know that if we are not as aggressive as we should be, the patients struggle more than perhaps some of the other subgroups. It’s also very interesting that some of the information has shown that using 2 oral medications in different pathways as soon after diagnosis as possible—what’s called upfront combination oral therapy, which was shown in the AMBITION trial to be beneficial to Group 1 PAH patients—also holds value in connective tissue disease. Based on that scientific information and personal experience, I advocate for patients with connective tissue disease—associated mild or intermediate PAH to start 2 oral drugs as early as possible after diagnosis. Obviously, if they’re sicker, they may have to be on an infusion therapy or triplet therapy.
For patients with liver disease and portopulmonary hypertension [POPH], the goal is not only to treat the pulmonary hypertension [PH] but also to allow the patient to safely receive a liver transplant. Ultimately, the problem is end-stage liver disease or hepatic cirrhosis. If that’s not remedied, even if you control and improve the pulmonary hypertension, patients are still at risk of having complications from cirrhosis or even dying from liver failure. The goal is to get pressures down to a certain level, typically a mean pulmonary artery pressure of 35 mm Hg or less, with low pulmonary vascular resistance and normal right ventricular function by echocardiography, which then allows the patients to safely receive a liver transplant.
We work carefully with our GI [gastrointestinal] hepatologists and our liver transplant surgeons. We discuss these patients carefully at multidisciplinary conferences regarding the best therapy and the goals of therapy that can get them in an appropriate condition such that they can undergo a liver transplant if they’re otherwise eligible, which has a very good chance of improving the pulmonary hypertension as well. It’s not a guarantee that pulmonary hypertension would go away completely, but there is often a very favorable response, at least allowing for less medication after the transplant. Certainly, patients feel better if their liver is now working properly.
For Group 4 chronic thromboembolic pulmonary hypertension [CTEPH], decisions around drug therapy really hinge on if the patient is eligible for surgery—pulmonary thromboendarterectomy—which if successful, has a very high cure rate. About 10% of patients may have persistent pulmonary hypertension after the surgery, so they may require ongoing medication. Almost always, the initial therapy in that group, if they’re not going to have surgery, is riociguat.
A new intervention that’s receiving more study is balloon pulmonary angioplasty. There is some information showing that it can have a very positive effect on pulmonary pressures and pulmonary vascular resistance with similar or even slightly better benefit than riociguat, based on 1 study. But remember, it’s an intervention, so it’s going to have complications. Complications can be severe when you’re working with a catheter in pulmonary circulation. The potential complications may balance out any potential improvement over drug therapy. That becomes an individualized decision between the physician and the patient. But we’re very excited about the possible role of balloon pulmonary angioplasty in these patients who would not otherwise be eligible for the more curative surgery, pulmonary thromboendarterectomy.