Acid suppressants use and risk of atherosclerotic cardiovascular disease in middle-aged and older adults

Background and aims: Concerns regarding adverse events associated with the use of acid suppressants have increased. However, the impact of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the risk of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to estimate the risk of ASCVD in association with the use of PPIs and H2RAs.

Methods: This prospective cohort study included participants without cardiovascular diseases or anti-hypertensive treatment at baseline (2006-2010) in the UK Biobank. The outcomes were ASCVD and each subtype (coronary artery disease, myocardial infarction, peripheral artery disease, and ischemic stroke). The association was estimated by Cox proportional-hazards models.

Results: Among 316,730 individuals (aged 50-88 years), during a median of 12.5 years of follow-up, we documented 13,503 (4.3%) incident ASCVD. Regular PPIs use was associated with a higher risk of ASCVD (HR: 1.16, 95% CI: 1.09-1.23) and every subtype of ASCVD. Among each type of PPIs, omeprazole (HR: 1.19, 95% CI: 1.11-1.28), lansoprazole (HR: 1.11, 95% CI: 1.02-1.22), and pantoprazole (HR: 1.40, 95% CI: 1.00-1.97) were associated with a higher risk of ASCVD. Stratification analysis showed that PPIs use was associated with a higher risk of ASCVD among individuals without indications of medications for PPIs. In addition, use of H2RAs was not related to the risk of ASCVD (HR: 0.97, 95% CI: 0.85-1.11).

Conclusions: PPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs.