Charles Burger, MD: We know actually from work that was done out of the REVEAL registry that patients with group 1 pulmonary arterial hypertension have a very high likelihood of being hospitalized soon after the diagnosis. Indeed, 57% of the patients are hospitalized at least once in the first year after diagnosis, and the majority of the reason is complications of the pulmonary arterial hypertension. So, it was very encouraging to look at several of these more recently published studies that have resulted in medication approval for pulmonary arterial hypertension. For example, SERAPHIN, which is a study of macitentan, had a composite endpoint that included pulmonary hypertension progression, hospitalization, need for transplant, and survival. These were significantly reduced both in the 3- and the 10-mg arms, but most predominantly in the 10-mg arm, which was the dose that was ultimately approved. And embedded in that was the reduction in hospitalizations, which drove a lot of that endpoint. It fit with the fact that we know these patients are at high risk for this problem and that the pharmacologic intervention reduced the rate of that hard endpoint. So, that was very encouraging.
Subsequent studies really have reinforced that. For example, if you look at GRIPHON, a study of close to 1200 patients with selexipag—which is a prostacyclin receptor agonist—its intervention in a dose-titrated study showed a reduction in a composite endpoint that included these hard endpoints that I mentioned in the SERAPHIN study. It then was analyzed subsequently by Dr. Channick and published in the Journal of American Cardiology Heart Failure manuscript, demonstrating, again, a very firm reduction that was demonstrated in the patients who took selexipag compared to the patients that did not.
Likewise, in AMBITION, which is an upfront combination therapy trial with tadalafil and ambrisentan, and just like the GRIPHON study and the SERAPHIN study, there was a composite endpoint. But, a very important reduction in that composite endpoint was keeping patients with PAH who were on combination upfront therapy out of the hospital at a higher rate than the patients that were on the single arm, essentially reducing the need for hospitalization, the expense of the hospitalization, the risk of hospitalization, and the inconvenience of the hospitalization to the patient. Clearly, this is a benefit that everybody should recognize from the patient, to the clinician, to the third-party payer, to the pharmacist, to the nurse. It has been very reassuring and quite obviously exciting for the pulmonary hypertension community that the pharmacologic therapies are having such a positive impact on our patients.