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.