INTRODUCTION We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control. METHODS We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables. RESULTS In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome. DISCUSSION Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

中文翻译：

---

质子泵抑制剂与心血管疾病风险：自控病例系列研究。

引言 我们使用自控病例系列 (SCCS) 研究设计、一种仅病例设计和一种克服人与人之间混淆的方法（其中个体作为自己的行为），调查了质子泵抑制剂 (PPI) 治疗引起的心血管风险控制。方法 我们使用韩国国民健康保险服务-健康筛查队列 (2002-2015) 进行了一项 SCCS 研究。该队列包括 303,404 名既往没有心血管事件的成年参与者，他们被随访至 2015 年 12 月。主要结局是中风或心肌梗死的复合结局。SCCS 方法估计了主要结局患者中暴露于 PPI 和未暴露于 PPI 期间的年龄调整发病率比率。作为敏感性分析，进行了传统的多变量 Cox 比例回归分析，将随访期间暴露于 PPI 和 H2 阻滞剂的情况视为时间相关变量。结果 在 SCCS 设计中，包括 10,952 名（3.6%）具有主要结局的患者。PPI 暴露与主要结局之间没有关联（发生率比 0.98，95% 置信区间 [CI] 0.89-1.09）。在时间依赖性 Cox 回归分析中，PPI（调整后的风险比 1.36，95% CI 1.24-1.49）和 H2 阻滞剂（调整后的风险比 1.46，95% CI 1.38-1.55）均与主要结局风险增加相关. 讨论 SCCS 设计中的负面发现表明，心血管风险增加与 PPI 之间的关联（在先前的观察性研究中经常报道）可能是由于与 PPI 治疗条件相关的残余混杂因素，而不是真正的关系。