Proton Pump Inhibitors Use and Risks of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes: A Prospective Study in the UK Biobank
During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease compared with nonuse of a PPI, after full adjustment for potential confounding variables.
The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in myocardial infarction, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.
The authors of the report speculate that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.
Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans
this study provides, for the first time, strong evidence that PPIs can per se promote heart rate–corrected QT interval prolongation, by directly inhibiting hERG function. A careful evaluation of the benefit/risk ratio is recommended whenever PPIs are administered in subjects with other QT-prolonging risk factors, even in the absence of hypomagnesemia.
PPI users had more QT-prolonging risk factors compared with PPI nonusers. Patients with multiple comorbidities are more likely to have polypharmacy including PPIs. The additional use of a PPI may be particularly harmful to these patients, more frequently burdened by preexisting QT-prolonging risk factors (and drug-drug interactions), because of synergistic effects on the ventricular repolarization.
In fact, by specifically focusing on the bivariate interaction existing between PPIs and each one of the other risk factors present, we found that in most cases, the PPI administration was associated with additional and significant QT-prolonging effects. Accordingly, multivariate adjustments for concomitant risk factors attenuated PPI-associated ORs for QTc prolongation.