Use of proton pump inhibitors is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nested case-control study.

Abstract

Proton pump inhibitors (PPIs) impair cardiac repolarization and prolong the QT interval and may potentially be proarrhythmic. However, risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We studied whether past or current PPI use is associated with OHCA in the general population. We conducted a nationwide nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA-controls from the general population. Exposure to PPI was categorized into three mutually exclusive groups of current-, past-, and non-use. Conditional logistic regression analyses with adjustments for risk factors of OHCA was used to calculate the odds ratio (OR) of OHCA comparing PPI use with non-users. We identified 46578 OHCA-cases and 232890 matched non-OHCA-controls (mean:71 years, 68.8% men). PPI was used by 8769 OHCA-cases and 21898 non-OHCA-controls, and current use of PPI was associated with increased odds of OHCA compared with non-users (OR:1.32 [95%-CI:1.28 -1.37]), while past use conferred no increase in the odds of OHCA (OR:1.01 [95%-CI:0.98-1.04]). This increased odds of OHCA occurred in both sexes. Finally, the ORs remained elevated when we repeated the analyses in individuals without registered ischemic heart disease (OR:1.36 [95%-CI:1.31-1.41]), without heart failure (OR:1.33 [95%-CI:1.29-1.38]), or without any cardiovascular comorbidities (OR:1.84 [95%-CI:1.70-2.00]). Also, the OR remained elevated when H2-antagonists served as the reference group (OR:1.28 [95%-CI:1.11-1.47]). PPI use is associated with an increased risk of OHCA in the general population. Considering the widespread use of PPIs, this study raises concerns and need for awareness to balance the benefit and risk of treatment.