title: Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome.
abstract: Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.
authors.affiliation: Department of Cardiology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miwa
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Uno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yasuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakata
authors.forename: Toyonobu
authors.initials: T
authors.lastname: Tsuda
authors.forename: Honin
authors.initials: H
authors.lastname: Kanaya
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D017675:CREST Syndrome / Q000150:complications*; D003451:Cryoprotective Agents; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D003451:Cryoprotective Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C048081:beraprost; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D015106:3',5'-Cyclic-GMP Phosphodiesterases