Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Cancer. 2021 Jun 1;127(11):1805-1815. doi: 10.1002/cncr.33412. Epub 2021 Jan 20.
Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA-NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication.
Adult patients who had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA-NSAID use (≥90 days) was treated as a time-dependent variable in a multivariable Cox model (time-dependent analysis). Time-independent analysis was also performed.
During a median follow-up of 8.9 years (interquartile range, 5.4-12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA-NSAID use was associated with a significant reduction in the risk of GC in time-fixed analysis (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.47-0.90), but not in time-dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97-1.87). Time-dependent subgroup analyses also did not indicate any significant association between NA-NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27-2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83-1.98).
NA-NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA-NSAIDs observed in prior studies may have been confounded by immortal time bias.
尽管已经根除了幽门螺杆菌（HP），但仍有个体可能会发展为胃癌（GC）。先前的研究表明，非阿司匹林类非甾体抗炎药（NA-NSAIDs）可降低 GC 的风险，但这可能是由于存在起始时间偏倚且未调整 HP 状态所致。本研究旨在探究 HP 根除后，NA-NSAIDs 是否可降低 GC 的发病风险。
从一项全港医疗数据库中，筛选出于 2003 年至 2016 年间接受克拉霉素三联疗法的成年患者。排除标准包括先前患有 GC 或 GC 在 HP 根除后 6 个月内确诊、既往胃切除术、HP 根除后的胃溃疡以及三联疗法失败。协变量包括年龄、性别、既往消化性溃疡病史、其他合并症和同时使用的药物（阿司匹林、质子泵抑制剂、他汀类药物和二甲双胍）。为避免起始时间偏倚，NA-NSAID 使用（≥90 天）在多变量 Cox 模型中被视为时间依赖性变量（时间依赖性分析）。同时还进行了时间不变性分析。
在中位随访 8.9 年（四分位间距，5.4-12.6 年）期间，92017 例接受 HP 根除治疗的患者中有 364 例（0.4%）发生了 GC。固定时间分析表明，NA-NSAID 使用与 GC 发病风险显著降低相关（校正后 HR，0.65；95%CI，0.47-0.90），但在时间依赖性多变量分析中不相关（校正后 HR，1.35；95%CI，0.97-1.87）。时间依赖性亚组分析也未提示 NA-NSAID 使用与贲门部 GC（校正后 HR，0.75；95%CI，0.27-2.06）或非贲门部 GC（校正后 HR，1.28；95%CI，0.83-1.98）之间存在任何显著关联。
HP 根除后，NA-NSAID 使用与 GC 发病风险降低无关。先前研究中观察到的 NA-NSAIDs 的化学预防作用可能受到起始时间偏倚的混杂。
