Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol

Circ J. 2005 Apr;69(4):461-5. doi: 10.1253/circj.69.461.


Background: Epoprostenol (prostaglandin I(2)) has become recognized as a therapeutic breakthrough that can improve hemodynamics and survival in patients with primary pulmonary hypertension (PPH). However, a significant number of patients have PPH that is refractory to epoprostenol, and lung transplantation has been the only remaining treatment option.

Methods and results: The study subjects included 20 consecutive patients with PPH (mean pulmonary arterial pressure: 65+/-15 mmHg) who had received epoprostenol for more than 12 months. The patients were divided into 2 groups; responders and non-responders. In the non-responders, New York Heart Association (NYHA) functional class did not improve and mean right atrial pressure (mRA) increased to 8 mmHg or more, and additional sildenafil, a phosphodiesterase-5 inhibitor, was started. Six patients were included in the non-responders, whose mRA was 9+/-5 mmHg before and significantly increased to 13+/-3 mmHg after epoprostenol administration (p < 0.05). One patient died and the other 5 patients received oral sildenafil. The mRA of 12+/-4 mmHg (value before sildenafil) improved to 8+/-5 mmHg after sildenafil administration. Three patients were classified in the NYHA functional class 4 and improved to class 3, and 2 patients were in class 3 and remained in the same class after the addition of sildenafil.

Conclusions: In patients with severe PPH refractory to epoprostenol treatment, additional oral sildenafil can improve pulmonary hemodynamics and symptoms. The combination therapy of epoprostenol and sildenafil is a new medical treatment to attempt before progressing to lung transplantation for patients with PPH refractory to epoprostenol.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Drug Resistance*
  • Drug Synergism
  • Drug Therapy, Combination
  • Epoprostenol / administration & dosage
  • Epoprostenol / therapeutic use*
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Purines
  • Salvage Therapy / methods
  • Sildenafil Citrate
  • Sulfones
  • Treatment Outcome


  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate
  • Epoprostenol