Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome.
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.
Miwa
Kenji
K
Department of Cardiology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
Matsubara
Takashi
T
Uno
Yoshihide
Y
Yasuda
Toshihiko
T
Sakata
Kenji
K
Tsuda
Toyonobu
T
Kanaya
Honin
H
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*
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