RESUMO
The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2. Clinical improvement was defined as ≥2 of the following in patients who completed the study without clinical worsening: ≥10% or ≥30 m improvement in 6-minute walking distance; World Health Organization functional class I or II; ≥30% decrease in N-terminal prohormone of brain natriuretic peptide. At PATENT-1 Week 12, patients treated with riociguat were more likely to achieve the composite endpoint vs. placebo (P < 0.0001), with similar results in pretreated (P = 0.0189) and treatment-naïve (P < 0.0001) patients. Achievement of the composite endpoint at Week 12 was associated with a 45% reduction in relative risk of death and a 19% reduction in relative risk of clinical worsening in PATENT-2. Overall, these data suggest that use of the REPLACE composite endpoint in patients with pulmonary arterial hypertension is a valid assessment of response to treatment.
RESUMO
OBJECTIVE: Some reports have documented a higher early mortality with the use of extended criteria donors in lung transplantation. None have evaluated how outcomes compare with the use of these organs for single and bilateral transplantation or whether this practice results in a higher incidence of early bronchiolitis obliterans syndrome. METHODS: We performed a retrospective review of case notes, intensive therapy unit database, and donor details. Between January 1, 2000, and December 31, 2004, 201 patients underwent lung or heart-lung transplantation. RESULTS: Eighty-three (41.3%) patients received organs deemed marginal on the basis of at least one of the following criteria: donor age greater than 55 years, duration of ventilation greater than 5 days, purulent secretions or inflammation at bronchoscopy, smoking of 20 or more cigarettes per day, abnormality on chest roentgenogram, or PO2/fraction of inspired oxygen ratio of less than 300 mm Hg immediately before donor organ procurement. Recipients of marginal lungs had a higher incidence of severe (grade 3) primary graft dysfunction (43.9% vs 27.4%, P = .015) and 90-day organ-specific mortality (15.7% vs 5.1%, P = .012). Bilateral transplantation carried a significantly higher 30-day mortality if performed with marginal organs (17.0% vs 2.7% with standard donor organs, P = .005). Thirty-day mortality was not significantly different for the transplantation of single marginal or standard donor lungs. Cumulative survival and survival free of bronchiolitis obliterans syndrome was not affected by marginal donor status. CONCLUSION: Transplantation of extended criteria donor lungs leads to a higher incidence of primary graft dysfunction. Bilateral transplantation with these organs seems to confer less reserve, resulting in a higher early mortality rate. Medium-term functional outcome is, however, not adversely affected by the relaxation of donor criteria.