Chest. 2011 Nov;140(5):1274-83. Epub 2011 May 5.
Long-Term Treatment with Sildenafil Citrate in Pulmonary Arterial Hypertension: SUPER-2.
Rubin LJ, Badesch DB, Fleming TR, Galiè N, Simonneau G, Ghofrani HA, Oakes M, Layton G, Serdarevic-Pehar M, McLaughlin VV, Barst RJ; on behalf of the SUPER-2 study group.
University of California at San Diego, La Jolla, CA.
Abstract
BACKGROUND: The long-term safety and tolerability of sildenafil treatment for pulmonary arterial hypertension (PAH) were assessed.
METHODS: 259 of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1) of oral sildenafil in treatment-naïve 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 were titrated to sildenafil 80 mg thrice daily (TID); 1 dose reduction for tolerability was allowed during the titration phase.
RESULTS: The median duration of sildenafil treatment across SUPER-1 and 2 was 1242 days (range, 1-1523 days); 170 (61%) patients 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 six-minute-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 was 79%; if all censored patients were assumed to have died, 3-year survival 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.
Clinical trials identifier: NCT00159887.
PMID: 21546436