Dual Therapy for Initial Treatment of Adult Patients With Pulmonary Arterial Hypertension

Key Messages

What Is the Issue?

• Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increases in pulmonary vascular resistance and pulmonary arterial pressure, which eventually lead to right-sided heart failure and death if left untreated.
• Decision-makers are interested in understanding the clinical effectiveness and safety of initial dual therapy in the treatment of patients with newly diagnosed PAH.

What Did We Do?

• We identified and summarized the literature published since 2015 on the evidence of the clinical effectiveness and safety of initial dual therapy in the treatment of patients with newly diagnosed or previously untreated PAH.

What Did We Find?

• We identified 3 relevant clinical studies. Two studies compared initial dual therapy with initial monotherapy, and 1 study compared initial triple therapy with initial dual therapy.
• Initial dual therapy with an endothelin-1 receptor antagonist (ERA) and a phosphodiesterase type 5 (PDE5) inhibitor had significant advantages in improving various clinical outcomes compared with monotherapy, particularly for patients at low to intermediate risk with idiopathic PAH or connective tissue disease (CTD)–associated PAH and WHO functional class (FC) II or III symptoms.
• Tolerability (withdrawal from the study due to adverse events [AEs]) was similar among patients receiving dual therapy or monotherapies, and the safety profile of dual therapy was consistent with the safety profiles of each monotherapy.
• Initial triple therapy and initial dual therapy each improved various clinical outcomes in patients with newly diagnosed PAH, with no difference between groups.

What Does This Mean?

• Initial combination therapy with 2 oral medications, an ERA and a PDE5 inhibitor, may provide better treatment outcomes in patients with PAH compared to monotherapy. However, there are limitations to the evidence that should be considered.