Clinical Pharmacology Unit, University of Edinburgh, The Queen׳s Medical Research Institute, Edinburgh, UK.
Pulmonary Hypertension and Heart Failure Clinic, Cliniques Universitaires de Bruxelles - Erasme Hospital, Brussels, Belgium.
J Heart Lung Transplant. 2014 May;33(5):521-7. doi: 10.1016/j.healun.2014.01.853. Epub 2014 Jan 23.
Elevated serum uric acid is detected in pulmonary arterial hypertension (PAH) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAH patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW) and survival.
In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2.
Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg and bosentan all reduced serum uric acid (p < 0.05). Reduced serum uric acid correlated with increased 6MWD (p = 0.0037).
Endothelin receptor antagonism reduces serum uric acid in PAH patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential.
肺动脉高压（PAH）患者的血清尿酸升高，与患者预后不良相关。高血清尿酸是心血管疾病和肾功能损害的独立危险因素。我们分析了内皮素受体拮抗剂对参加西他生坦缓解运动不耐受（STRIDE）-2/2X 试验的 PAH 患者的血清尿酸的影响，以及尿酸对 6 分钟步行距离（6MWD）、临床恶化时间（TtCW）和生存的影响。
在 18 周、双盲、安慰剂对照的 STRIDE-2 试验中，246 名 PAH 患者被随机分为匹配的安慰剂组、西他生坦 50 或 100mg 每日口服一次组或开放标签波生坦 125mg 每日口服两次组。STRIDE-2X 是 STRIDE-2 的为期 1 年的开放标签扩展研究。
基线时各组的血清尿酸相似。血清尿酸升高是 1 年死亡率和 TtCW 的显著危险因素。与安慰剂相比，西他生坦 50 和 100mg 以及波生坦均可降低血清尿酸（p<0.05）。血清尿酸降低与 6MWD 增加相关（p=0.0037）。
内皮素受体拮抗剂可降低 PAH 患者的血清尿酸，这种降低与生存时间延长和 TtCW 延长相关。需要进一步的前瞻性研究来探讨血清尿酸在 PAH 中的致病作用及其预后潜力。
