Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut.
Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut2Section of Digestive Diseases, Department of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven.
JAMA Intern Med. 2014 Nov;174(11):1755-62. doi: 10.1001/jamainternmed.2014.4056.
Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.
To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.
Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.
Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).
Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.
The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.
The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.
Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.
目前的指南建议在接受内镜治疗的高危出血性溃疡患者中，静脉推注质子泵抑制剂（PPI）后再持续输注 PPI。如果间断性 PPI 治疗与推注加持续输注 PPI 治疗同样有效，则可减少 PPI 剂量、降低成本并减少资源使用。
比较间断性 PPI 治疗与目前推荐的推注加持续输注 PPI 方案，以降低溃疡再出血率。
检索了 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册数据库，截至 2013 年 12 月；2009 年至 2013 年美国和欧洲胃肠病学会议摘要；以及系统评价的参考文献。
比较内镜治疗的高危出血性溃疡（活动性出血、非出血可见血管和附着的血栓）患者的随机试验，比较了间断 PPI 剂量和目前推荐的方案（80mg PPI 静脉推注剂量，然后以 8mg/h 的速度输注 72 小时）。
进行了重复的独立数据提取和偏倚风险评估。如果存在统计学异质性，则使用固定效应模型或随机效应模型进行数据合并。
主要结果是 7 天内再出血；其他预先设定的结果包括 3 天和 30 天内再出血、需要紧急干预、死亡率、红细胞输注和住院时间。在开始文献综述之前就确定了主要假设，即间断使用 PPI 与推注加持续输注 PPI 相比非劣效，非劣效性边界预先设定为绝对风险差异 3%。
与推注加持续输注 PPI 相比，间断性 PPI 治疗 7 天内再出血的风险比为 0.72（单侧 95%CI 的上限为 0.97），绝对风险差异为-2.64%（单侧 95%CI 的上限为-0.28%，远低于预先设定的非劣效性边界 3%）。30 天和 3 天内再出血、死亡率和紧急干预的风险比小于 1，输血和住院时间的平均差异小于 0，这表明间断治疗没有增加风险的汇总估计。所有预先设定的再出血结局的绝对风险差异的 95%CI 上限均小于 1.50%。
在内镜治疗的高危出血性溃疡患者中，间断性 PPI 治疗与目前指南推荐的静脉推注加持续输注 PPI 方案同样有效。指南应进行修订以推荐间断性 PPI 治疗。
