Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
Aliment Pharmacol Ther. 2018 Aug;48(4):469-477. doi: 10.1111/apt.14895. Epub 2018 Jun 29.
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may reduce the risk of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus; however, current epidemiologic studies are inconclusive.
To evaluate the independent effects of PPIs and H2RAs on risk of OAC in patients with Barrett's oesophagus.
We conducted a nested case-control study of male veterans diagnosed with Barrett's oesophagus. Cases with incident OAC were matched by incidence density sampling on birth year and Barrett's diagnosis date to controls with Barrett's oesophagus who did not develop OAC. We identified prescription medication usage 1 year prior to Barrett's oesophagus diagnosis to 3 months prior to the OAC diagnosis. Odds ratios (OR) and 95% CI were estimated using conditional logistic regression.
Compared with 798 controls, the 300 cases were less likely to use PPIs (90.0% vs 94.5%, P = 0.01) and H2RAs (19.7% vs 25.7%, P = 0.04). In the multivariable model including the use of statins, H2RAs, aspirin and nonsteroidal anti-inflammatory drugs, PPI use was associated with 41% lower risk of OAC (OR 0.59, 95% CI 0.35-0.99). While risk reduction of OAC was stronger for high-dose PPIs (omeprazole daily dose >40 mg, adjusted OR 0.11, 95% 0.04-0.36), we did not find a dose-response relationship with PPI duration (P trend = 0.45). Likewise, H2RA use was independently associated with 30% lower risk of OAC (OR 0.70, 95% CI 0.50-0.99).
Use of PPIs and H2RAs among patients with Barrett's oesophagus are associated with lower risk of OAC. Further clinical trials are needed to confirm this possible chemopreventive effect.
质子泵抑制剂（PPIs）和组胺-2 受体拮抗剂（H2RAs）可能降低巴雷特食管中食管腺癌（OAC）的风险；然而，目前的流行病学研究尚无定论。
评估 PPIs 和 H2RAs 对巴雷特食管患者 OAC 风险的独立影响。
我们对诊断为巴雷特食管的男性退伍军人进行了一项嵌套病例对照研究。通过按出生年份和巴雷特食管诊断日期进行发病率密度抽样，将患有 OAC 的病例与未发生 OAC 的巴雷特食管对照进行匹配。我们确定了在巴雷特食管诊断前 1 年至 OAC 诊断前 3 个月期间的处方药物使用情况。使用条件逻辑回归估计比值比（OR）和 95%置信区间（CI）。
与 798 名对照相比，300 名病例使用 PPI（90.0% vs. 94.5%，P=0.01）和 H2RA（19.7% vs. 25.7%，P=0.04）的可能性较小。在包括他汀类药物、H2RA、阿司匹林和非甾体抗炎药使用的多变量模型中，PPI 使用与 OAC 风险降低 41%相关（OR 0.59，95%CI 0.35-0.99）。虽然高剂量 PPI（奥美拉唑每日剂量>40mg，调整后的 OR 0.11，95%CI 0.04-0.36）的 OAC 风险降低作用更强，但我们没有发现与 PPI 持续时间（P 趋势=0.45）之间存在剂量反应关系。同样，H2RA 使用与 OAC 风险降低 30%相关（OR 0.70，95%CI 0.50-0.99）。
在巴雷特食管患者中使用 PPI 和 H2RA 与 OAC 风险降低相关。需要进一步的临床试验来证实这种可能的化学预防作用。
