Association between regular proton pump inhibitors use and cardiovascular outcomes: A large prospective cohort study

Background: Proton pump inhibitors (PPIs) are widely prescribed for gastroesophageal reflux disease and peptic ulcer disease. However, the association between the regular PPIs use and the risk of cardiovascular disease (CVD) outcomes remains unclear. We aimed to determine whether regular proton pump inhibitors (PPIs) use is associated with an altered incidence of cardiovascular disease (CVD) in the general population. Methods: This prospective cohort study included 459,207 participants (mean [SD] age, 56.2 [8.1] years) from the UK Biobank study without prevalent CVD who enrolled between 2006 and 2010 and were followed until 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD and its components (coronary heart disease [CHD], stroke, heart failure, atrial fibrillation, and venous thromboembolism) were obtained using Cox proportional hazards models with adjustment for potential confounding factors, including demographic factors, lifestyle behaviors, prevalent comorbidities, and clinical indicators for PPIs use. Results: During the follow-up period, we recorded 26,346 incident CVD events (including 13,749 CHD events, 4144 stroke events, 5812 atrial fibrillation events, 1159 heart failure events, and 4206 venous thromboembolism events). The fully adjusted HRs (and 95% CIs) associated with PPIs users compared to nonusers were 1.44 (95% CI 1.39–1.50) for incident CVD, 1.65 (95% CI 1.57–1.74) for CHD, 1.21 (95% CI 1.09–1.33) for stroke, 1.17 (95% CI 1.08–1.28) for atrial fibrillation, 1.61 (95% CI 1.37–1.89) for heart failure, and 1.36 (95% CI 1.24–1.50) for venous thromboembolism. Conclusions: Regular PPIs use was associated with higher risk of CVD outcomes. Clinicians should therefore exercise caution when prescribing PPIs.