Andreana Foresta, Luisa Ojeda Fernandez, Ginevra Torrigiani, Simone Schena, Maria Carla Roncaglioni, Alessandro Nobili, Mauro Tettamanti, Carlotta Franchi, Ida Fortino, Elena Succurro, Giorgio Sesti, Marta Baviera
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引用次数: 0
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
背景据报道，质子泵抑制剂（PPI）对一般人群的心血管（CV）预后和死亡率有不利影响。方法利用伦巴第大区的行政健康数据库，我们分析了2015年接触过质子泵抑制剂并随访至2021年的糖尿病患者（年龄≥65岁）发生心肌梗死（MI）、缺血性中风和总死亡率的风险。采用多变量调整的考克斯比例危险模型对结果进行分析，计算出危险比（HR）和95%置信区间（CI）。还估算了特定亚组中使用 PPI 者与未使用 PPI 者之间的 HRs。此外，还在 1:1 倾向评分匹配人群中进行了敏感性分析。与未使用 PPI 的患者相比，使用 PPI 的患者合并症和用药率更高。在中位 6.7 年的随访期间，使用 PPI 与较高的缺血性中风（HR 1.14，95% CI 95% 1.08-1.20）、心肌梗死（HR 1.36，95% CI 1.31-1.41）和总死亡率（HR 1.24，95% CI 1.22-1.26）风险相关。无论使用哪种PPI，PPI使用者的这些风险都较高。在性别、既往心血管疾病和胰岛素亚组中，男性、无心血管疾病史者和未接受胰岛素治疗者使用 PPIs 与缺血性中风风险显著增加有统计学关联。除既往有心血管疾病史的患者外，所有亚组的心肌梗死风险以及总死亡率都与服用干粉吸入剂明显相关。我们的研究结果证实，在大量接触过 PPIs 的糖尿病老年人群中，冠心病事件和全因死亡率的风险增加。这可能会对公共卫生和国民健康服务成本产生重要影响，因此建议定期评估 PPI 的适宜性，尤其是在这一人群中。
期刊介绍：
Drugs & Aging delivers essential information on the most important aspects of drug therapy to professionals involved in the care of the elderly.
The journal addresses in a timely way the major issues relating to drug therapy in older adults including: the management of specific diseases, particularly those associated with aging, age-related physiological changes impacting drug therapy, drug utilization and prescribing in the elderly, polypharmacy and drug interactions.
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