title: Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension.
abstract: Pulmonary arterial hypertension (PAH) is characterized by abnormalities in endothelial and smooth muscle cell function. Prostacyclin released by endothelial cells is a potent vasodilator by increasing cyclic adenosine monophosphate. Sildenafil, an inhibitor of phosphodiesterase-5, increases cyclic guanosine monophosphate in the lungs, producing vasodilation. To test for a therapeutic benefit of the combination of a prostacyclin analogue, subcutaneous treprostinil, and sildenafil, a proof-of-concept, open-label investigational trial was initiated. Subjects with PAH in World Health Organization (WHO) functional classes II to IV receiving subcutaneous treprostinil for > or =6 months were evaluated with an exercise treadmill test using the Naughton-Balke protocol at baseline and after 12 weeks. Sildenafil 50 mg 3 times daily was added to the treprostinil. Mean treadmill times in seconds were compared before and after 12 weeks of therapy. Nine subjects enrolled in the trial; 7 were women (mean age 35 years). At baseline, 3 subjects were in WHO functional class II and 6 subjects were in WHO functional class III. The mean treadmill time at baseline was 465 +/- 167 seconds and at 12 weeks was 656 +/- 205 seconds (42% improvement, p = 0.049). All patients had symptomatic improvement. In conclusion, this pilot study of subcutaneous treprostinil with sildenafil for PAH suggests additive beneficial effects.
authors.affiliation: University of Chicago Hospitals, Chicago, Illinois, USA. mgomberg@medicine.bsd.uchicago.edu
authors.forename: Mardi
authors.initials: M
authors.lastname: Gomberg-Maitland
authors.forename: Vallerie
authors.initials: V
authors.lastname: McLaughlin
authors.forename: Martha
authors.initials: M
authors.lastname: Gulati
authors.forename: Stuart
authors.initials: S
authors.lastname: Rich
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines; D012189:Retrospective Studies; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C427248:treprostinil