Gastrointestinal Ulceration in Patients on Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Background and Significance:

Percutaneous coronary intervention (PCI) is the standard of care for patients with acute coronary syndrome (ACS). Approximately 1,200,000 PCIs were performed in 2002 in the United States. Drug-eluting coronary stents have nearly abolished the clinical problem of in-stent restenosis at a cost of increased susceptibility to in-stent thrombosis, a catastrophic event associated with a 6-month mortality rate of 8.9% and a myocardial infarction rate that exceeds 50%.

To prevent in-stent thrombosis, PCI patients receive aspirin 325 mg and a minimum loading dose of clopidogrel 300 mg prior to stent deployment. In actual practice, many patients are now receiving a clopidogrel loading dose of 600 mg to ensure adequate platelet inhibition. Muller et al showed that administration of a higher loading dose (600mg) of clopidogrel to patients undergoing PCI accelerates suppression of platelet aggregation when evaluated by aggregometry. When patients were given a higher loading dose (600mg) of clopidogrel as opposed to the conventional loading dose (300mg), there was a 50% reduction in myocardial infarction after PCI in patients who received the higher dose. If a 600 mg loading dose of clopidogrel is adopted as routine practice, there may be a further increase in the risk of major gastrointestinal (GI) ulceration.

In multivariable analysis, the strongest predictor of stent thrombosis is premature discontinuation of dual antiplatelet therapy, exceeding other independent predictors such as renal failure, bifurcation lesions, diabetes, and low ejection fraction. Hence, following PCI with drug-eluting stents, dual antiplatelet therapy, with aspirin 75 to 162 mg lifelong in combination with clopidogrel 75 mg for at least 3 months, is prescribed.

The risk of overt GI bleeding with dual antiplatelet therapy can be as high as 1.3% within the first 30 days of therapy. Weil et al found that all doses of aspirin were associated with an increased risk of GI bleeding and that the risk of GI bleeding due to low-dose aspirin was dose-related: odds ratio 2.3 for 75 mg ⁄day; 3.2 for 150 mg ⁄day; 3.9 for 300 mg ⁄day. In the Clopidogrel for Unstable angina to prevent Recurrent Events (CURE) study, Peters et al showed that the risk of bleeding at the highest dose of aspirin (≥ 200mg) given with placebo was higher (3.7 %) than the risk of GI bleeding with the combination of clopidogrel and aspirin in the lowest dose group (3.0 %).