Leandro G, Pilotto A, Franceschi M, Bertin T, Lichino E, Di Mario F
Gastroenterological Hospital S. De Bellis, IRCCS, Castellana Grotte (BA), Italy.
Dig Dis Sci. 2001 Sep;46(9):1924-36. doi: 10.1023/a:1010687115298.
No consensus exists as to whether cotherapy is effective in the short-term prevention of severe NSAID-related gastroduodenal damage. The aim of this study was to provide a quantitative systematic review of the efficacy of gastroprotective drugs, such as misoprostol, H2-blockers, and proton pump inhibitors (PPI) in preventing the severe acute NSAID-related gastroduodenal damage. Placebo-controlled randomized clinical trials on the use of misoprostol, H2-blockers, and PPIs as preventative agents published between January 1986 and May 1999 were identified through Medline and reference lists from clinical reviews. Studies on patients or healthy subjects were considered to be eligible for data pooling if they were performed in acute NSAID users (not longer than 30 days) and with at least one endoscopic evaluation during therapy that reported results specifically for gastric and duodenal damage. Risk difference (RD), heterogeneity chi2 test, publication bias assessment and number needed to treat (NnT) were calculated for each meta-analysis by a customized program. Twenty-one trials met the inclusion criteria evaluating a total of 636 healthy subjects and 1904 patients with arthritis randomized to active drug or placebo. The baseline risk of NSAID-related gastric (68% vs 16.6%, P < 0.001) and duodenal (22% vs 8.5%, P < 0.001) damage was higher in healthy subjects compared to patients with arthritis. Meta-analysis demonstrated a significant heterogeneity between trials performed in the two populations (P < 0.0001). In healthy subjects the active drug treatment induced a significant prevention of severe gastric (misoprostol RD = 69%, 95% CI = 60.3-77.7, H2-blocker RD = 38.3%, 95% CI = 17.8-58.9 and PPI RD = 43%, 95% CI = 28.2-57.7) and duodenal damage (misoprostol RD = 22.3%, 95% CI = 13.6-31, H2-blocker RD = 13.2%, 95% CI = 5.2-21.3 and PPI RD = 17.7%, 95% CI = 3.5-31.8). NnT values were, respectively, 1, 3, and 2 for gastric and 4, 8, and 6 for duodenal damage. In patients with arthritis lower RD and higher NnT values were found compared to healthy subjects. In conclusions, cotreatment with gastroprotective drugs for short-term prevention of severe gastroduodenal NSAID-related damage was more effective in healthy subjects than in patients with arthritis; misoprostol and PPIs were more effective than H2-blockers in the prevention of both gastric and duodenal severe damage; more studies need to evaluate the role of short-term prevention in patients with arthritis who require acute NSAID treatment.
关于联合治疗在短期预防非甾体抗炎药（NSAID）相关严重胃十二指肠损伤方面是否有效，目前尚无共识。本研究的目的是对胃黏膜保护药物，如米索前列醇、H2受体阻滞剂和质子泵抑制剂（PPI）预防严重急性NSAID相关胃十二指肠损伤的疗效进行定量系统评价。通过医学文献数据库（Medline）以及临床综述的参考文献列表，确定了1986年1月至1999年5月期间发表的关于使用米索前列醇、H2受体阻滞剂和PPI作为预防药物的安慰剂对照随机临床试验。如果研究是在急性NSAID使用者（用药时间不超过30天）中进行，并且在治疗期间至少有一次内镜评估报告了胃和十二指肠损伤的具体结果，则这些针对患者或健康受试者的研究被认为有资格进行数据汇总。通过一个定制程序对每项荟萃分析计算风险差异（RD）、异质性卡方检验、发表偏倚评估和需治疗人数（NnT）。21项试验符合纳入标准，共评估了636名健康受试者和1904名关节炎患者，这些患者被随机分配至活性药物组或安慰剂组。与关节炎患者相比，健康受试者中NSAID相关胃损伤（68%对16.6%，P<0.001）和十二指肠损伤（22%对8.5%，P<0.001）的基线风险更高。荟萃分析表明，在这两类人群中进行的试验之间存在显著异质性（P<0.0001）。在健康受试者中，活性药物治疗显著预防了严重胃损伤（米索前列醇RD=69%，95%CI=60.3 - 77.7，H2受体阻滞剂RD=38.3%，95%CI=17.8 - 58.9，PPI RD=43%，95%CI=28.2 - 57.7）和十二指肠损伤（米索前列醇RD=22.3%，95%CI=13.6 - 31，H2受体阻滞剂RD=13.2%，95%CI=5.2 - 21.3，PPI RD=17.7%，95%CI=3.5 - 31.8）。胃损伤的NnT值分别为1（米索前列醇）、3（H2受体阻滞剂）和2（PPI），十二指肠损伤的NnT值分别为4（米索前列醇）、8（H2受体阻滞剂）和6（PPI）。与健康受试者相比，关节炎患者的RD值更低，NnT值更高。总之，联合使用胃黏膜保护药物短期预防严重NSAID相关胃十二指肠损伤在健康受试者中比在关节炎患者中更有效；米索前列醇和PPI在预防胃和十二指肠严重损伤方面比H2受体阻滞剂更有效；需要更多研究来评估短期预防在需要急性NSAID治疗的关节炎患者中的作用。
