Inhaled Treprostinil for Treatment of Chronic Pulmonary Arterial Hypertension

TO THE EDITOR:

Background: Treprostinil is a stable prostacyclin analogue that is approved for the treatment of pulmonary arterial hypertension when administered by continuous subcutaneous infusion (1). Inhalation of the stable prostacyclin analogue iloprost has proven clinical efficacy in patients with pulmonary hypertension in a randomized, controlled trial (2).

Objective: To characterize the effects of inhaled treprostinil with special regard to safety, tolerability, and efficacy in patients with severe pulmonary arterial hypertension.

Methods and Findings: Three patients with severe pulmonary hypertension underwent catheterization of the right heart and femoral artery for evaluation of pulmonary and systemic hemodynamics. The protocol consisted of assessment of baseline values; administration of nitric oxide at a concentration of 20 parts per million; and administration of a single 15-µg dose of treprostinil, inhaled in 3 breaths through a modified OptiNeb ultrasonic inhalation device (Nebu-Tec, Elsenfeld, Germany). All 3 patients had severe pulmonary hypertension; mean pulmonary vascular resistance (±SE) was 1355±286 dyne/s per cm⁻⁵. Inhalation of nitric oxide resulted in a mean reduction (±SE) in pulmonary vascular resistance of 26% ±22.8%. Inhalation of treprostinil substantially reduced pulmonary vascular resistance (mean maximum change [±SE], −45.2% ±17.5%) for a sustained period (duration of effect, >180 min). Pulmonary selectivity of the approach was reflected by a substantially reduced ratio of pulmonary vascular resistance to systemic vascular resistance; the mean area under the curve (±SE) was 30% ±11% for pulmonary resistance and 16% ±3% for systemic resistance. One patient had a favorable vasodilator response (shown in the Figure) and was therefore given high-dose calcium-channel blocker therapy.