Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea.
Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
Eur J Clin Pharmacol. 2023 Dec;79(12):1699-1708. doi: 10.1007/s00228-023-03580-7. Epub 2023 Oct 20.
To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk.
We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users.
After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users.
In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.
阐明长期使用质子泵抑制剂（PPI）是否会增加胃癌（GC）风险。
我们在韩国国家健康保险服务数据库中检索了 2009 年至 2019 年期间年龄大于 40 岁的患者，这些患者在 2009 年至 2014 年期间声称进行了幽门螺杆菌根除（HPE）。比较了 PPI 暴露量大于 180 个累积定义日剂量（cDDD）和暴露量小于 180 cDDD 的 GC 发生率。结果为 HPE 后至少 1 年发生 GC。在相同随访时间四分位区间内，使用倾向评分（PS）匹配数据集进行分析。此外，评估了剂量-反应关系，并比较了长期 PPI 使用者和非使用者的死亡率。
在 PS 匹配后，分析了 144091 对 PPI 使用者和非使用者。在中位随访 8.3 年（四分位间距 6.8-9.6 年）期间，PPI 使用者和非使用者中分别有 1053 例和 948 例 GC 病例，GC 发病率（95%置信区间（CI））分别为 0.90（0.85-0.96）和 0.81（0.76-0.86）/1000 人年。PPI 使用的 GC 调整后的危险比（aHR）为 1.15（95%CI，1.06-1.25）。在 PPI 使用者中，每年 PPI 剂量最高三分位的患者 GC 发展率高于最低三分位的患者（aHR（95%CI）：3.87（3.25-4.60））。PPI 使用者和非使用者之间的 GC 相关死亡率无显著差异。
在韩国这个 GC 发病率较高的国家进行的这项全国性分析中，HPE 后长期使用 PPI 与 GC 显著增加相关，且存在正剂量反应关系。
