Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), College of Medicine, Mayo Clinic, Rochester, MN, USA.
Aliment Pharmacol Ther. 2014 Feb;39(3):239-53. doi: 10.1111/apt.12571. Epub 2013 Dec 5.
Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC).
To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC.
We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI).
Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride.
Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT4 agonists in the treatment of chronic constipation.
高度选择性 5-HT4 激动剂已被推荐用于治疗慢性便秘（CC）。
评估高度选择性 5-HT4 激动剂（普芦卡必利、velusetrag 或 naronapride）对慢性便秘患者重要的临床疗效结局和安全性的影响。
我们于 2013 年 1 月使用 MEDLINE/Pubmed、Embase、Cochrane 图书馆和 Web of Science/Scopus 对高度选择性 5-HT4 激动剂治疗成人慢性便秘的随机对照试验进行了文献检索，无最低治疗时间（最长 12 周）或日期限制。数据从意向治疗分析中提取，使用随机效应模型进行汇总，并以相对风险（RR）、平均差异或标准化平均差异（SMD）及 95%置信区间（CI）表示。
主要结局包括粪便频率、便秘患者生活质量评估（PAC-QOL）、症状 PAC（PAC-SYM）和不良事件。确定了 13 项符合条件的试验：11 项普芦卡必利，1 项 velusetrag，1 项 naronapride。与对照组相比，高度选择性 5-HT4 激动剂治疗在所有结局方面均有优势：每周至少 3 次自发完全排便（RR=1.85；95%CI 1.23-2.79）；与基线相比至少 1 次自发完全排便（RR=1.57；95%CI 1.19，2.06）；PAC-QOL 和 PAC-SYM 评分至少改善 1 分。唯一一项普芦卡必利与 PEG3350 的活性比较试验表明，PEG3350 在某些终点上更有效。高度选择性 5-HT4 激动剂的不良反应更为常见，但通常较轻；头痛是最常见的。大多数试验研究了普芦卡必利。
在重要的患者结局上显示出疗效，且具有良好的安全性特征，支持高度选择性 5-HT4 激动剂继续用于治疗慢性便秘。
