Are diagnostics and drugs optimized for pulmonary hypertension?
A new study from Cleveland Clinic investigators show a repeated inhaled nitric oxide challenge in patients with pulmonary hypertension provide variable responses—showing less pronounced acute pulmonary vasoreactivity which may be associated with both disease progression with fixed remodeling and potentially vascular reserve-limiting therapies.
The findings, presented at the CHEST 2019 Annual Meeting in New Orleans, evidence the need for improved, varied therapies in pulmonary hypertension.
In an interview with MD Magazine®, investigator Adriano R. Tonelli, MD, of the Department of Pulmonary, Allergy and Critical Care Medicine at the clinic’s Respiratory Institute, expanded on his team’s findings, and what improved pulmonary hypertension therapies may look like.
MD Mag: Does the limited option of pulmonary hypertension drugs warrant the assessment of current diagnostic studies?
Tonelli: You're completely right. The therapies are mainly based on 3 pathways that were described 20 years ago: the prostacyclin, nitric oxide, the endothelin pathway. And all the medications we have are mostly vasodilators acting on those pathways. And new medications are needed.
One purpose of the study that we did is by repeating the nitric oxide challenge, one can test whether the changes in plasticity of the lung. One would think that by giving these therapies that may affect the characteristics of the vessel and making it a little bit more plastic, they may have, vasodilation but we couldn't see that.
MD Mag: How do these findings directly impact pulmonary hypertension patients?
Tonelli: The study doesn't directly impact patients, but it tells us that there are changes that occur over time, and that the therapies that we have right now are not acting very much in the remodeling of the vessels—obtaining what would be ideal. They’re not reverse remodeling up to normal.
So newer therapies are certainly needed. This emphasized the need for newer therapies that will act in a different way than the 3 ones that we mentioned—particularly in decreasing proliferation, and able to take this the abnormal circulation to a normal one.
MD Mag: Regarding care: what potential pulmonary hypertension drugs are you most looking forward to?
Tonelli: There are several medications been tested that act in different pathways. I'm pretty excited with the study of the medications that activate the BMPR2 pathway, such as tacrolimus, sotatercept—those medications that have a more mechanistic target with good preclinical data. I think they have a good chance of success.
Also medications that work in metabolic pathways, because the metabolism is altered with increase in the glycolysis. So medications that act in that sense may also be effective. And other medications—tyrosine kinase inhibitors may be a very attractive.
All those are more acting on the process of the disease's proliferation, the thickening of the intima, the proliferation of the media and adventitia. So, acting more on different pathways—more pathways that influence the proliferation progression of the disease, I think will be the future.
Another agent, that is distinctive from the 3 ones that we have, another group of medications will be very important for the patient in the future.