Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy.
Unità Organizzativa Osservatorio Epidemiologico Regionale, Lombardy Region, Milan, Italy.
Drugs Aging. 2024 Mar;41(3):239-249. doi: 10.1007/s40266-024-01097-x. Epub 2024 Feb 17.
The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing.
Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population.
A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort.
Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.
质子泵抑制剂 (PPIs) 对心血管 (CV) 结局和死亡率的不利影响已在普通人群中报道。我们研究了 PPI 在糖尿病 (DM) 老年人中的 CV 结局和全因死亡率的影响，因为这方面的证据尚不足。
我们使用伦巴第大区的行政健康数据库，分析了 2015 年暴露于 PPI 的年龄≥65 岁的 DM 患者的心肌梗死 (MI)、缺血性卒中和全因死亡率的风险。使用多变量调整的 Cox 比例风险模型分析结局，计算风险比 (HR) 及其 95%置信区间 (CI)。还在选定的亚组中估计了 PPI 使用者与非使用者之间的 HR。还在 1:1 倾向评分匹配人群中进行了敏感性分析。
共纳入 284068 例患者（49.4%为 PPI 使用者，50.6%为非 PPI 使用者）。与非使用者相比，PPI 使用者的合并症和药物治疗的发生率更高。在中位随访 6.7 年期间，PPI 的使用与缺血性卒中（HR 1.14，95%CI 95% 1.08-1.20）、MI（HR 1.36，95%CI 1.31-1.41）和全因死亡率（HR 1.24，95%CI 1.22-1.26）的风险增加相关。无论 PPI 类型如何，PPI 使用者的这些风险均更高。在男性、无 CV 病史和未接受胰岛素治疗的亚组中，PPI 的使用与缺血性卒中的风险增加相关，而在所有亚组中，PPI 的使用与 MI 的风险增加相关，并且与全因死亡率相关，除了有 CV 病史的患者。敏感性分析证实了未匹配队列的结果。
我们的研究结果证实，在接受 PPI 治疗的大量老年 DM 患者中，CV 事件和全因死亡率的风险增加。这可能对国民健康服务体系的公共卫生和成本产生重要影响，因此建议定期评估 PPI 的适宜性，特别是在该人群中。
