Rostom A, Wells G, Tugwell P, Welch V, Dube C, McGowan J
University of Ottawa Department of Medicine, A1 - Endoscopy Unit, Ottawa Hospital - Civic Campus, 1053 Carling Ave., Ottawa, Ontario, Canada, K1Y-4E9.
Cochrane Database Syst Rev. 2000;2002(3):CD002296. doi: 10.1002/14651858.CD002296.
Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.
To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.
A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted.
Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included.
Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test.
Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.
REVIEWER'S CONCLUSIONS: Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications.
非甾体抗炎药（NSAIDs）是治疗关节炎和炎症性疾病的重要药物，在北美和欧洲是最常处方的药物之一。然而，有大量证据表明这些药物与多种胃肠道（GI）毒性有关。
综述预防NSAID引起的上消化道毒性的常见干预措施的有效性。
根据Cochrane方法在电子数据库中检索随机对照试验，包括1966年至2000年1月的MEDLINE、2000年1月前6个月的《现刊目次》、截至1999年2月的Embase，并检索1973年至1999年的Cochrane对照试验注册库。查阅了近期会议论文集，并联系了内容专家和相关公司。
纳入前列腺素类似物（PA）、H2受体拮抗剂（H2RA）或质子泵抑制剂（PPI）预防慢性NSAID引起的上消化道毒性的随机对照临床试验（RCTs）。
两名独立的审阅者提取了有关人群特征、研究设计、方法学质量以及内镜下溃疡、溃疡并发症、症状、总体退出人数、因症状退出人数的患者数据。使用Revman V3.1汇总二分数据。使用卡方检验评估异质性。
33项RCTs符合纳入标准。所有剂量的米索前列醇均显著降低内镜下溃疡风险。米索前列醇800μg/天预防内镜下胃溃疡优于400μg/天（RR分别为0.18和0.38，p = 0.0055）。十二指肠溃疡未观察到剂量反应关系。米索前列醇在所有剂量下均引起腹泻，尽管800μg/天比400μg/天腹泻更明显（p = 0.0012）。米索前列醇是唯一被证明可降低溃疡并发症风险的预防药物。标准剂量的H2RAs可有效降低内镜下十二指肠溃疡风险（RR = 0.24；95%CI：0.10 - 0.57），但对胃溃疡无效（RR = 0.73；95%CI：0.50 - 1.09）。双倍剂量的H2RAs和PPIs均可有效降低内镜下十二指肠和胃溃疡风险（胃溃疡的RR分别为0.44；95%CI：0.26 - 0.74和RR = 0.37；95%CI：0.27 - 0.51），且耐受性优于米索前列醇。
米索前列醇、PPIs和双倍剂量的H2RAs可有效预防慢性NSAID相关的内镜下胃和十二指肠溃疡。较低剂量的米索前列醇效果较差且仍与腹泻有关。仅米索前列醇800μg/天已被直接证明可降低溃疡并发症风险。
