The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China.
Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
BMC Med. 2021 Dec 3;19(1):316. doi: 10.1186/s12916-021-02180-5.
Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk.
This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method).
We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively.
Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.
虽然随机对照试验（RCT）表明质子泵抑制剂（PPI）使用者中风的风险增加，但这一关联尚未得到证实。我们评估了常规使用 PPI 与中风事件的相关性，并确定了高净风险人群。
这是一项对英国生物库中 492479 名无中风参与者的前瞻性分析。通过使用国际疾病分类（ICD）-10 代码（I60、I61、I63 和 I64）与住院和死亡登记处进行链接，确定中风事件。我们通过调整人口统计学因素、生活方式习惯、现患合并症、同时使用药物和 PPI 的指征，评估了风险比（HR）。我们根据基线Framingham 中风风险评分评估了风险差异（RD）。在荟萃分析中，我们检索了 PubMed、EMBASE 和 Cochrane 对照试验中心注册库（1988 年至 2020 年 6 月 1 日），比较了 PPI 与其他干预措施、安慰剂或无治疗对中风风险的影响。使用固定效应荟萃分析（Mantel-Haenszel 法）对结果进行合并。
我们在 3935030 人年的随访中记录了 5182 例中风事件。与非使用者相比，常规 PPI 使用者的中风风险增加了 16%（HR 1.16，95%CI 1.06 至 1.27）。这一估计效果与我们对 9 项 RCT 的荟萃分析相似（病例/参与者 371/26642；RR 1.22，95%CI 1.00 至 1.50；证据质量：中等）。PPI 使用对中风的影响随着基线Framingham 中风风险评分的增加而增加，在 5 年内，最低、四分位数 2、四分位数 3 和最高四分位数的 RD 分别为 1.34‰、3.32‰、4.83‰和 6.28‰。
常规使用 PPI 与中风风险增加相关，在基线中风风险较高的人群中观察到更高的绝对风险。因此，医生在开具 PPI 时应谨慎。建议对潜在的中风风险进行评估，以个体化使用 PPI。
