Background
Proton pump inhibitors (PPIs) are widely used drugs for gastric-acid-related diseases, which may have an impact on the gut microbiome. We aimed to evaluate the associations of PPI use with risks of cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D).
Methods
We analysed the associations of PPI use with risks of coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality in 19,229 adults with T2D using data from the UK Biobank study.
Results
During a median follow-up of 10.9-11.2 years, we documented a total of 2,971 CAD, 1,827 MI, 1,192 HF, and 738 stroke cases, along with 2,297 total deaths. PPI use was significantly associated with higher risks of CAD (HR, 1.27; 95% CI, 1.15-1.40), MI (HR, 1.34; 95% CI, 1.18-1.52), HF (HR, 1.35; 95% CI, 1.16-1.57) and all-cause mortality (HR, 1.30; 95% CI, 1.16-1.45). No significant association was observed between PPI use and stroke (HR, 1.11; 95% CI, 0.90-1.36). The results were consistent in the subgroup analyses stratified by factors including indications of PPI, anti-diabetic medication use, and antiplatelet drug use. Analyses in a 1:1 propensity score-matched cohort of PPI users versus non-users yielded similar results.
Interpretation
Our data suggested that PPI use was associated with higher risks of CVD events and mortality among patients with T2D. The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced.