Proton pump inhibitors (PPIs) are a type of medication that reduce stomach acid production. As a result, they are a commonly used to treat conditions caused by too much stomach acid, such as peptic ulcer disease, or to protect the stomach lining alongside medicines that may irritate it. PPIs are effective in reducing symptoms related to the aforementioned conditions and are considered safe by the wider medical community. However, some studies suggest that long-term PPI use may cause health problems further down the line that are underappreciated by doctors ahead of prescription; these range from direct effects on the gut as well as indirect effects on other organs, such as the heart. Due to a lack of research in this area, these effects are not well understood currently. Our study aims to change this by researching the effects of years of PPI use among patients in the United Kingdom. In particular, we will look into whether long-term use of PPIs are related to weight gain, heart conditions (such as abnormal heart rhythms) and other related measures. Improving our knowledge in this area is likely to trigger further research down the line, which will stands to benefit the general public in several ways: by stopping unnecessary long-term PPI prescriptions, diverting funds to other in-need areas of healthcare, and identifying these medicines as factor in some patients’ chronic health conditions.
Proton pump inhibitors (PPI) are commonly prescribed for both their significant symptomatic as well as therapeutic benefits (such as in peptic ulcer disease). However, their deleterious effects are rarely appreciated in clinical practice; whilst various studies in the literature have elucidated links to gastric carcinomas and impaired absorption of various electrolytes, the scale of these issues alongside various other potential sequelae of use (including cardiac disease and weight gain) have not been extensively investigated. Therefore, we propose that ubiquitous PPI prescriptions may be associated with significant morbidity; our overarching aims are to study the incidence and prevalence of deleterious effects (which will be considered the primary exposures) related to chronic PPI use such as weight gain, dyselectrolytaemia and/or dysrhythmia. The study population of interest will be adults who are actively taking prescribed PPIs for at least 1 year.
A multivariate statistical analysis will be undertaken to assess the incidence of the aforementioned comorbidities amongst chronic PPI users; they will be actively compared against patients who use histamine 2 receptor antagonists to minimise confounding by indication. Due to multiple covariates being studied, a cox proportional hazards model will be used to investigate the association between chronic PPI use and onset of these conditions. BMI data extracted from the CPRD will be age adjusted and analysed over time to observe temporal weight trends from initiation of prescription, as an exploratory analysis. ‘Hospital Episode Statistics’ will be used to determine hospitalisations for dyselectrolytaemias and dysrhythmias (e.g. those presenting in atrial fibrillation with a rapid ventricular rate). The bulk of our analysis will be observational by commenting on observed trends, and is therefore speculative. Elucidating a significant burden of deleterious effects secondary to PPI use will ultimately lead to rationalising long-term PPI prescriptions, leading to significant cost savings as well as reducing disease burden.
Primary outcome measures:
The primary outcome of this study will be the association between long term PPI use and rates of previously defined comorbidities:
1)Weight gain (defined as ≥5% increase in body weight).
2)Hypomagnasaemia (defined as serum magnesium measurements of <0.8 mmol/L).
3)Atrial fibrillation (including both paroxysmal and persistent).
Secondary outcomes to be measured:
1)Temporal trends of BMI in long-term PPI use between 1997 to 2017.
Joseph Shalhoub - Chief Investigator - Imperial College London
Becker Al-Khayatt - Corresponding Applicant - Imperial College London
HES Accident and Emergency;HES Admitted Patient Care