Personalized, Aggressive Care for Pulmonary Arterial Hypertension


The addition of a couple of new drug classes at the turn of the century have given clinicians the greenlight to stack therapies at initial treatment.

It took more than a quarter-century, but clinicians have finally progressed from a single available intravenous (IV) therapy intended to delay the chronic symptoms of pulmonary arterial hypertension (PAH), to a trio of drug classes with varying processes of care.

In an interview with MD Magazine® while at the 2018 CHEST Annual Meeting in San Antonio, TX, Gary Palmer, MD, MBA, Vice President of Medical Affairs for Actelion Pharmaceuticals and Victor Tapson, MD, Director of the Venous Thromboembolism & Pulmonary Vascular Disease Research Program at the Cedars-Sinai Medical Center, explained how each addition to the PAH market—up to the recently approved endothelin receptor antagonist (ERA) macitentan (OPSUMIT)—has bolstered care and given physicians the ability to switch from defensive to offensive treatment.

MD Mag: What does tailored care look like in PAH?

Tapson: Back in the 90s, we had 1 drug, it was prenyl prostacyclin. It was cumbersome; you had to give it by IV. Early 2000, we came up with an ERA, placetin, and subsequently, PDE-5 inhibitors. So over the last couple of decades, we now have 3 classes of medication, several medications in each class, so much more to choose from. And we tend to be more aggressive nowadays.

This is still considered a fatal disease. So, even though patients may seem stable and do OK, we want to get them to a place where they're doing well. We tend to be, in a nutshell, using drugs upfront and adding a second or third drug more commonly nowadays than we used to, because we have them available.

Palmer: I would agree. I think that things have moved from monotherapy to dual therapy, and now increasingly to triple therapy—and in a similar way that other diseases have done so. In the past, we used to wait for patients to deteriorate before we added things on.

Increasingly, we're finding that maybe intervening earlier is better for patients. This is a rapidly declining disease, and if we can slow the rate of decline, patients have fewer morbidity events over time, and actually have better quality of life living with this deadly disease.

MD Mag: What is the value of ERAs?

Tapson: So, macitentan is an endothelin receptor antagonist. We've got selective and non-selective antagonists. Macitentan is the newest one we have. It's approved based on the SERAPHIN study. We're using it more and more—it's 10 mg once a day, so an easy drug to use.

We also have the PDE-5 inhibitors sildenafil and tadalafil. We also have several prostanoid therapies, including the oral prostacyclin receptor agonist selexipag, which we discussed earlier. Several classes of drugs, ERAs like macitentan—a major classification which we're using in virtually all our patients.

Palmer: A characteristic of this disease is that the arteries which supply the blood from the right side of the heart to the lungs get progressively thickened and tighter. So, one of the key mechanisms for all these drugs as a vasodilator is to allow the blood to get to the lungs, where it picks up oxygen.

It's done by 3 different mechanisms, so there are drugs in 3 different categories. Essentially, in different ways, we're looking to dilate the arteries so we can allow the blood to get to the lungs.

Tapson: Endothelin is a very potent restrictor. I tell patients they have millions of little hair-sized vessels in their lungs—narrow, tiny, little vessels. They get narrowed and constricted, and we've got millions of vessels doing this, and the right ventricle can't get blood pumped into the lungs. It's enlarged, it's dilated, hypofunctional, and it fails. So ERAs are drugs that help open up these vessels.

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