Use of proton-pump inhibitors (PPIs) is suggested to be associated with adverse cardiovascular (CV) events via. endothelial dysfunction. Studies show that PPIs are associated with increased risk of myocardial infarction (MI) among patients with preexisting CV disease. However, little is known about their risk among people without known CV disease.
We conducted a nested case–control study in the UK Clinical Practice Research Datalink (CPRD) GOLD to evaluate the association between PPI use and risk of MI in patients without known CV disease. From among PPIs users age 25 to 65 between 1988 and 2017, we identified 32,793 MI cases and 127,291 controls matched 4:1 on age, sex, general practice setting, and calendar time. Using logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for MI comparing PPI users to nonusers, adjusting for body mass index, smoking, alcohol abuse, drug abuse, type 2 diabetes, hyperlipidemia, hypertension, and peripheral artery disease. We repeated this analysis in users of histamine 2 receptor antagonists (H2RA), a drug with a similar indication, to assess protopathic bias.
The risk of MI was elevated in new users of PPIs with one to five prescriptions (adjusted OR = 2.8; 95% CI = 2.6, 3.0), but not in any other exposure category. The results among H2RA users were similar across all exposure categories, suggesting that protopathic bias likely explains the results.
Our study results were not consistent with the hypothesis that PPI use increases MI risk among people without known heart disease.