Although there is presently no cure for PH, significant advances have been made in treatment options, and this has resulted in increased survival compared to that seen in the 1980s.8 Dr. Gomberg-Maitland discussed several diagnostic algorithms that have been developed to identify intermediate- to high-risk patients and quickly connect these patients to referral centers that focus on PH, and she urged the audience to consider employing such algorithms in their clinical practice.9
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Dr. Gomberg-Maitland discussed the pathways that have been explored in PAH therapeutic trials over the past four decades, beginning with the use of early conventional therapies (i.e., supplemental oxygen, calcium channel blockers and vasodilators) and progressing to involve the prostacyclin, endothelin and nitric oxide pathways. She stressed that some treatment options are often underutilized, such as digoxin, to increase contractility in right heart failure and reduce sympathetic nervous system activation, and diuretics, to reduce peripheral edema, intravascular volume and venous pressure.
Twelve medications are currently approved by the U.S. Food & Drug Administration for the treatment of PAH, and it is likely the cadre of available treatments will continue to expand.
An important point raised in the talk was that no single class of drug has proved to be consistently effective in the treatment of PAH in all patients, implying that no single pathway exists to explain all cases. With this in mind, it is rational to consider combination therapy with more than one agent in order to target several different disease pathways at the same time.
In an event-driven, double-blind, randomized, controlled trial of 500 patients with WHO functional class II or III symptoms of PAH who had not previously received treatment, initial combination therapy with ambrisentan (i.e., a potent type-A selective endothelin receptor antagonist) and tadalafil (i.e., an inhibitor of phosphodiesterase type 5, also known as PDE5) resulted in a significantly lower risk of clinical failure events than ambrisentan or tadalafil monotherapy.10 These types of trials have informed, and will continue to inform, decisions on which patients should receive combination therapy.
Dr. Gomberg-Maitland also described work she has been involved with on the Pulmonary Hypertension Outcomes Risk Assessment (PHORA) tool. This multi-platform clinical decision support system uses data from the REVEAL Registry to risk stratify patients with PAH and help guide therapeutic decisions and optimize clinical trial design using advanced computer learning and data mining technology. In a 2020 paper on this tool, researchers demonstrated this Bayesian, network-derived risk prediction model (compared with existing models) could discriminate between low-, intermediate- and high-risk PAH groups.11