1. Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension.
- Author
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Simonneau G, Rubin LJ, Galiè N, Barst RJ, Fleming TR, Frost A, Engel P, Kramer MR, Serdarevic-Pehar M, Layton GR, Sitbon O, and Badesch DB
- Subjects
- Administration, Intravenous, Adult, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Follow-Up Studies, Hemodynamics physiology, Humans, Hypertension, Pulmonary mortality, Hypertension, Pulmonary physiopathology, Longitudinal Studies, Male, Middle Aged, Outcome Assessment, Health Care, Purines therapeutic use, Sildenafil Citrate, Survival Rate, Time Factors, Treatment Outcome, Walking physiology, Antihypertensive Agents administration & dosage, Antihypertensive Agents therapeutic use, Epoprostenol administration & dosage, Epoprostenol therapeutic use, Hypertension, Pulmonary drug therapy, Phosphodiesterase 5 Inhibitors therapeutic use, Piperazines therapeutic use, Sulfonamides therapeutic use
- 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., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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