Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension

Gérald Simonneau*, Lewis J. Rubin, Nazzareno Galiè, Robyn J. Barst, Thomas R. Fleming, Adaani Frost, Peter Engel, Mordechai R. Kramer, Marjana Serdarevic-Pehar, Gary R. Layton, Olivier Sitbon, David B. Badesch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background In pulmonary arterial hypertension (PAH), adding oral sildenafil to intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics and delayed time to clinical worsening in a 16-week randomized, placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of Epoprostenol and Sildenafil [PACES-1]). Methods Patients completing PACES-1 could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in an open-label extension study (PACES-2) for ≥3 years; additional therapy was added according to investigator judgment. Survival and changes from PACES-1 baseline in World Health Organization Functional Class and 6MWD were captured. Results In an open-label setting, 6MWD, an effort-dependent outcome measure, was known to have improved or to have been maintained in 59%, 44%, and 33% of patients at 1, 2, and 3 years, respectively; functional class was known to have improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of patients were known to be alive, 24% were known to have died, and 10% were lost to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD improvement during the first 20 weeks of sildenafil treatment subsequently had poorer survival. Conclusions Although reliable assessments of safety and efficacy require a long-term randomized trial, the addition of sildenafil to background intravenous epoprostenol therapy appeared generally to be well tolerated in PAH patients.

Original languageEnglish
Pages (from-to)689-697
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume33
Issue number7
DOIs
StatePublished - Jul 2014
Externally publishedYes

Funding

FundersFunder number
Pfizer

    Keywords

    • clinical trial
    • epoprostenol
    • pulmonary arterial hypertension
    • sildenafil
    • survival

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