ABSTRACT
Until the turn of the century, intravenous epoprostenol was the only drug licensed for pulmonary arterial hypertension (PAH). The approval of bosentan in 2001 opened a new treatment era represented predominantly by oral drugs (i.e., endothelin receptor antagonists [ERAs] and phosphodiesterase-5 [PDE5] inhibitors). Combination therapies became almost instantly utilized once these new drugs became available, and international PAH guidelines mentioned the use of combination regimens as early as 2004 (1). However, it took another 10 years until robust evidence supporting the use of combination therapy became available (2).
