What are the treatment options for functional class II or III pulmonary arterial hypertension (PAH)?

Updated: Apr 25, 2018
  • Author: Kristin E Schwab, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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For patients with WHO functional class II or III disease, experts often begin with a combination of two oral agents targeting separate pathways. The combination of ambrisentan and tadalafil is the most frequently used combination and was approved as first-line treatment by the US Food and Drug Administration (FDA) in October 2015 based on the AMBITION trial. [29] The trial involved 605 patients with WHO functional class II or III PAH. Patients were randomly assigned to receive once-daily ambrisentan plus tadalafil or to either drug alone. Doses were titrated from 5-10 mg/day for ambrisentan and from 20-40 mg/day for tadalafil. Treatment with the combination was associated with an approximately 50% reduction in risk for clinical failure compared with either drug alone (P = .0002), with improved exercise ability as well as decreased disease progression and hospitalization. [29]

Other trials have looked at other combinations as well. In a controlled study of 25 patients with IPAH and scleroderma-associated PAH in whom monotherapy with bosentan had failed and sildenafil was added, a significant improvement in WHO functional status and exercise capacity was observed in patients with IPAH but not in the patients with scleroderma-associated PAH. [30] In another controlled trial, sildenafil 80 mg was added to an intravenous epoprostenol regimen, and the combination proved to be more effective than placebo for improving exercise capacity and pulmonary arterial pressure. [31] It also demonstrated a significant reduction in the number of patients showing clinical worsening and an improvement of survival among the patients with the most severe disease.

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