Anti‐platelet therapy and managing ulcer risk

Low‐dose aspirin (ASA) has emerged as one of the most important causes of peptic ulcer bleeding in developed countries. Among the risk factors of ASA‐associated ulcer bleeding, Helicobacter pylori infection is one of the few that is treatable. Recent evidence showed that among patients with a history of ASA‐associated ulcer bleeding, the long‐term incidence of recurrent bleeding with ASA use is low after eradication of H. pylori alone. Thus, test‐and‐treat H. pylori is a potentially useful strategy for ASA users with high ulcer risk. However, the risk of bleeding is further increased by combining other anti‐platelet drugs (e.g. clopidogrel) with ASA in acute coronary syndromes and coronary stent placement. There is good evidence that co‐therapy with a proton‐pump inhibitor (PPI) reduces upper gastrointestinal bleeding with ASA alone or dual anti‐platelet therapy. Recently, several meta‐analyses of observational studies found that concurrent use of PPI and clopidogrel was associated with increased risk of major adverse cardiovascular events. Overall, the evidence does not suggest a clinically important interaction between PPIs and clopidogrel. However, there is a subset of patients who have reduced conversion of clopidogrel to its active metabolites due to genetic polymorphism of hepatic P‐450 (carriers of CYP2C19 loss‐of‐function alleles). Since PPIs are also metabolized by similar hepatic enzymes, it is uncertain whether patients carrying CY2C19 loss‐of‐function alleles are susceptible to concomitant PPI use. In the future, management of patients on dual anti‐platelet therapy needs to be individualized according to their thrombotic and bleeding risks.