Proton‐pump inhibitor use and the development of new ischemic heart disease in non‐cardiac chest pain patients

BACKGROUND: The growing reports regarding cardiac-related adverse events of chronic proton-pump inhibitors (PPI) treatment, a mainstay therapy of non-cardiac chest pain (NCCP), have raised concerns about alteration of the natural course in NCCP patients using PPI. We aimed to determine if NCCP patients receiving PPI have a higher risk of developing ischemic heart disease (IHD) compared to those not receiving PPI therapy. METHODS: Three groups of NCCP patients were included; PPI, histamine-2 receptor antagonist (H2RA), and no antireflux treatment. Diagnosis of NCCP had to precede diagnosis of IHD by at least 30 days, and in those receiving antireflux treatment at 30 days after starting the medication. Data analysis was corrected for 6 known confounding factors for IHD including hyperlipidemia, hypertension, obesity, smoking status, male gender, and diabetes mellitus. KEY RESULTS: Of the patients on PPI or H2RA, 1280 and 250, respectively, developed IHD. Patients on PPI therapy displayed an increased odd of developing ischemic heart disease compared to patients never placed on therapy (OR 1.14, 95% CI 1.03-1.25, P-value .0093). Patients placed on H2RA therapy did not show a statistically significant change in risk compared to patients who were not placed on therapy (OR 0.90, 95% CI 0.77-1.06, P-value .2049). Number needed to harm in the PPI and H2RA groups was 17 and 45, respectively. CONCLUSIONS: PPIs confer a statistically significant, but marginal effect on the risk of IHD development in NCCP patients. Thus, PPI use in NCCP only minimally alters the overall benign natural course of the disease.