title: Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol.
abstract: 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.
  
  
  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.
authors.affiliation: Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Toru
authors.initials: T
authors.lastname: Satoh
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Manabe
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Mitamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines; D016879:Salvage Therapy / Q000379:methods; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol