Anti-platelet therapy and managing ulcer risk

J Gastroenterol Hepatol. 2012 Feb;27(2):195-9. doi: 10.1111/j.1440-1746.2011.07029.x.

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.

Publication types

  • Lecture
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Aspirin / adverse effects*
  • Aspirin / pharmacokinetics
  • Clopidogrel
  • Combined Modality Therapy
  • Cytochrome P-450 CYP2C19
  • Drug Interactions
  • Enzyme Inhibitors / therapeutic use
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / pathogenicity
  • Humans
  • Patient Selection
  • Peptic Ulcer / chemically induced
  • Peptic Ulcer / microbiology
  • Peptic Ulcer / prevention & control*
  • Peptic Ulcer Hemorrhage / chemically induced
  • Peptic Ulcer Hemorrhage / microbiology
  • Peptic Ulcer Hemorrhage / prevention & control*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / pharmacokinetics
  • Proton Pump Inhibitors / therapeutic use*
  • Risk Assessment
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin