CLINICAL SIGNIFICANCE OF DRUG–DRUG INTERACTIONS BETWEEN PROTON PUMP INHIBITORS AND CARDIOVASCULAR MEDICATIONS IN GERIATRIC PATIENTS: A SYSTEMATIC REVIEW

Abstract

Background: Proton pump inhibitors (PPIs) are commonly prescribed in older adults to prevent gastrointestinal bleeding, particularly in patients receiving antiplatelet or anticoagulant therapy. However, their potential interactions with cardiovascular drugs especially clopidogrel have raised concerns regarding adverse cardiovascular outcomes.

Objectives: This systematic review aimed to evaluate the clinical significance of PPI–cardiovascular drug interactions in geriatric patients, focusing on pharmacodynamic effects, cardiovascular outcomes, and implications for clinical practice.

Methods: A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library was conducted from January 2010 to January 2025. Eligible studies included randomized controlled trials, cohort, and case-control studies involving adults aged ≥60 years prescribed PPIs with antiplatelet or anticoagulant therapy. Data extraction followed PRISMA 2020 guidelines, with study quality assessed using the Cochrane RoB 2.0 tool and Newcastle–Ottawa Scale.

Results: Fifteen studies met inclusion criteria. Evidence indicated that omeprazole consistently attenuates clopidogrel’s antiplatelet activity, while pantoprazole and other PPIs demonstrated minimal interaction. Observational studies reported conflicting associations between PPI use and major adverse cardiovascular events (MACE), with hazard ratios ranging from no effect to a 70% increased risk. Randomized trial data showed limited clinical impact, though long-term PPI use was linked with increased cardiovascular disease and mortality in some large cohorts. Importantly, prophylactic PPIs reduced gastrointestinal bleeding and improved adherence to dual antiplatelet therapy in high-risk geriatric patients.

Conclusions: The cardiovascular significance of PPI use in geriatric patients is heterogeneous and context-dependent. Omeprazole should be avoided with clopidogrel when alternatives such as pantoprazole are available. Long-term PPI use warrants caution due to possible associations with cardiovascular disease and mortality. Individualized prescribing and careful risk–benefit assessment are critical in older adults where polypharmacy is common.