What is the efficacy of sildenafil for the treatment of 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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Answer

The antiproliferative effects of the phosphodiesterase type 5 (PDE5) pathway, which regulates cyclic guanosine monophosphate (cGMP) hydrolysis, is significant in the long-term treatment of PAH. Agents may include sildenafil, tadalafil, and vardenafil.

Sildenafil promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in a subsequent reduction of blood pressure in pulmonary arteries and an increase in cardiac output. It is dosed as a three-times-a-day medication. Its main adverse effects include headache, flushing, and epistaxis, which are likely related to its vasodilatory properties. Sildenafil has been studied as a single agent in PAH in multiple trials. [59, 60, 61, 62] In one randomized controlled trial evaluating 278 patients treated with sildenafil for 12 weeks, patients demonstrated improved 6-minute exercise capacity, reduced mean pulmonary arterial pressure, and a decrease in WHO functional class for a 12-month period. [59] An uncontrolled study of 104 CTEPH patients treated with sildenafil for 12 months documented significant improvements in WHO functional class and pulmonary vascular resistance. [61] It has also been studied as an additive agent with epoprostenol, and again showed improved 6MWD in this trial. [31]


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