title: Anti-platelet therapy and managing ulcer risk.
abstract: 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.
authors.affiliation: Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong. fklchan@cuhk.edu.hk
authors.forename: Francis K L
authors.initials: FK
authors.lastname: Chan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D018579:Patient Selection; D010437:Peptic Ulcer / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin