Lewis J Rubin1, David B Badesch2, Thomas R Fleming3, Nazzareno Galiè4, Gerald Simonneau5, Hossein A Ghofrani6, Michael Oakes7, Gary Layton7, Marjana Serdarevic-Pehar7, Vallerie V McLaughlin8, Robyn J Barst9. 1. Department of Medicine, University of California at San Diego, La Jolla, CA. Electronic address: ljrubin@ucsd.edu. 2. Department of Medicine, University of Colorado Denver, Denver, CO. 3. Department of Biostatistics, University of Washington, Seattle, WA. 4. Institute of Cardiology, University of Bologna, Bologna, Italy. 5. Centre des Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Clamart Cedex, France. 6. Medical Clinic II/V, University Hospital Giessen and Marburg GmbH, Justus-Liebig-University, Giessen, Germany. 7. Pfizer Global Research Division, Pfizer Ltd, Sandwich, England. 8. Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI. 9. Columbia University College of Physicians and Surgeons, New York, NY.
Abstract
BACKGROUND: The long-term safety and tolerability of sildenafil treatment of pulmonary arterial hypertension (PAH) were assessed. METHODS:Two hundred fifty-nine of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1 [Sildenafil Use in Pulmonary Arterial Hypertension]) of oral sildenafil in treatment-naive patients with PAH (96% functional class II/III) and entered an open-label uncontrolled extension study (SUPER-2) that continued until the last patient completed 3 years ofsildenafil treatment. Patients titrated to sildenafil 80 mg tid; one dose reduction for tolerability was allowed during the titration phase. RESULTS: The median duration of sildenafil treatment across SUPER-1 and SUPER-2 was 1,242 days (range, 1-1,523 days); 170 patients (61%) completed both studies, and 89 patients discontinued from SUPER-2. After 3 years, 87% of 183 patients on treatment were receiving sildenafil 80 mg tid. Of patients remaining under follow-up, 3%, 10%, and 18% were receiving a second approved PAH therapy at 1, 2, and 3 years, respectively. At 3 years post-SUPER-1 baseline, 127 patients had an increased 6-min walk distance (6MWD); 81 improved and 86 maintained functional class. Most adverse events were of mild or moderate severity. At 3 years, 53 patients had died (censored, n = 37). Three-year estimated survival rate was 79%; if all censored patients were assumed to have died, 3-year survival rate was 68%. No deaths were considered to be treatment related. CONCLUSIONS: Long-term treatment of PAH initiated as sildenafil monotherapy was generally well tolerated. After 3 years, the majority of patients (60%) who entered the SUPER-1 trial improved or maintained their functional status, and 46% maintained or improved 6MWD.
RCT Entities:
BACKGROUND: The long-term safety and tolerability of sildenafil treatment of pulmonary arterial hypertension (PAH) were assessed. METHODS: Two hundred fifty-nine of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1 [Sildenafil Use in Pulmonary Arterial Hypertension]) of oral sildenafil in treatment-naive patients with PAH (96% functional class II/III) and entered an open-label uncontrolled extension study (SUPER-2) that continued until the last patient completed 3 years of sildenafil treatment. Patients titrated to sildenafil 80 mg tid; one dose reduction for tolerability was allowed during the titration phase. RESULTS: The median duration of sildenafil treatment across SUPER-1 and SUPER-2 was 1,242 days (range, 1-1,523 days); 170 patients (61%) completed both studies, and 89 patients discontinued from SUPER-2. After 3 years, 87% of 183 patients on treatment were receiving sildenafil 80 mg tid. Of patients remaining under follow-up, 3%, 10%, and 18% were receiving a second approved PAH therapy at 1, 2, and 3 years, respectively. At 3 years post-SUPER-1 baseline, 127 patients had an increased 6-min walk distance (6MWD); 81 improved and 86 maintained functional class. Most adverse events were of mild or moderate severity. At 3 years, 53 patients had died (censored, n = 37). Three-year estimated survival rate was 79%; if all censored patients were assumed to have died, 3-year survival rate was 68%. No deaths were considered to be treatment related. CONCLUSIONS: Long-term treatment of PAH initiated as sildenafil monotherapy was generally well tolerated. After 3 years, the majority of patients (60%) who entered the SUPER-1 trial improved or maintained their functional status, and 46% maintained or improved 6MWD.
Authors: John M Dopp; Alexei V Agapitov; Christine A Sinkey; William G Haynes; Bradley G Phillips Journal: Am J Hypertens Date: 2013-02-26 Impact factor: 2.689