Supplementary Material for: H2 Receptor Antagonists versus Proton Pump Inhibitors in Patients on Dual Antiplatelet Therapy for Coronary Artery Disease: A Systematic Review

Objectives: Mitigating the gastrointestinal (GI) bleeding risks of dual antiplatelet therapy (DAPT) is a common clinical concern. While proton pump inhibitors (PPIs) remain the most effective therapy, their adverse events warrant considering alternatives, including Histamine 2 receptor antagonists (H2RAs). Methods: We searched for randomized controlled trials in MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials, published from 1980 to 2016. After screening, 10 trials were eligible. We compared PPIs to H2RAs in patients on DAPT in terms of 2 clinical and one laboratory outcomes; GI complications, major adverse cardiovascular events (MACE) and high on-treatment platelet reactivity (HTPR). Clinical and statistical inter-study heterogeneity was low for all 3 outcomes (I² = 0%, p > 0.05 for all). Results: Fixed effects meta-analysis suggested that PPIs were superior to H2RAs in preventing GI complications (OR 0.28, 95% CI 0.17–0.48) but with higher risk of HTPR (OR 1.28, 95% CI 1.030–1.60) though without a higher incidence of MACE (OR 0.99, 95% CI 0.55–1.77). Conclusions: PPIs are superior to H2RAs for gastroprotection in patients on DAPT. However, PPIs are associated with HTPR, with no significant difference demonstrated in MACE. Based on currently available data, the use of PPIs may be warranted in selected patients on DAPT deemed at risk for GI complications.