IMPACT OF PROTON PUMP INHIBITOR USE IN THE PREVENTION OF DUAL ANTIPLATELET THERAPY-ASSOCIATED UPPER GASTROINTESTINAL BLEEDING; A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Background
Dual antiplatelet therapy (DAPT) with oral P2Y12 inhibitors and aspirin is crucial for patients with acute coronary syndrome (ACS) and for those who are post-percutaneous coronary interventions (PCIs). However, gastrointestinal bleeding is a major limiting factor that often leads to increased morbidity and mortality. Concomitant proton pump inhibitor (PPI) therapy with DAPT can potentially reduce gastrointestinal (GI) bleeding risk, though there is paucity of data regarding the impact of PPI therapy on cardiovascular outcomes. We conducted a systematic review and meta-analysis to explore the effects of PPI on outcomes of DAPT use.

Methods
A comprehensive literature review was conducted using PubMed, Embase, Google Scholar, ClinicalTrials.gov, Scopus, and OVID for studies from inception until November 10, 2023. Patients who were 18 years and older and were on DAPT for at least 2 continuous weeks were included. Using the random-effects Mantel-Haenszel method, we calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) for all dichotomous variables.

Results
Six studies comprising 6,620 patients (PPI 3,301 and non-PPI 3,319) met inclusion criteria. Mean age was 64.2 years, 70% of the patients were males. Patients who received PPI therapy had less upper GI bleeding (RR=0.39, 95% CI[0.25-0.62], p<0.0001, I²=5%) and all-cause mortality (RR=0.46, 95% CI[0.27-0.80], p=0.005, I²=0%) as compared to patients in non-PPI group (Figure 1). However, the relative risk for major adverse cardiovascular events (MACE) (RR=0.87, 95% CI[0.69-1.10], p=0.26, I²=0%) and myocardial infarction (MI) (RR=0.93, 95% CI[0.75-1.14], p=0.47, I²=0%) was similar between PPI and non-PPI groups (Figure 2).

Conclusion
Our findings suggest that adding PPI therapy to DAPT significantly lowers the risk of upper GI bleeding and all-cause mortality, without adversely affecting major cardiovascular outcomes.