Problems Arising From the Prolonged Use of Aspirin and Clopidogrel Imposed by Drug-Eluting Stents / Conundrums in Triple Antithrombotic Therapy: Newer Suggestions

Abstract

Dual antiplatelet therapy (DAT) can decrease effectively the rate of major adverse cardiovascular events after drug-eluting stent (DES) implantation in high-risk coronary artery disease (CAD) patients, but its implementation is associated with excess in bleeding events compared with aspirin monotherapy and a considerable treatment failure rate, namely persistence of occurrence of ischemic events, despite the use of the recommended dosage of the standard DAT. All large-scale antiplatelet randomized controlled trials have shown that the prolonged administration of DAT after coronary stenting provides improved thrombotic prevention at a cost of increased bleedings.

            Newer antiplatelet regimens including higher maintenance doses of clopidogrel, or using the newer agents, prasugrel or ticagrelor, can effectively reduce rates of myocardial infarction and stent thrombosis during follow-up of high-risk CAD patients undergoing an invasive therapy, but they are accompanied by an increase in bleeding rates and, except for ticagrelor plus aspirin, do not reduce mortality. Therefore, the challenge remains to develop therapies that more effectively inhibit platelet activation and have a beneficial net effect on mortality without increasing bleeding complications.

            For patients receiving triple therapy, they are advised to keep the dose of aspirin as low as possible (75 to 81 mg); clopidogrel should be given at its standard dose of 75 mg/day, and warfarin should be administered under tight control to achieve a slightly lower target INR of 2.0 to 2.5. It is also suggested that proton-pump inhibitors (PPIs) should be considered as prophylaxis against gastric bleeds, tending to use pantoprazole and esomeprazole, which have the least incriminating data regarding an interaction with clopidogrel. In patients with mild or moderate bleeding while on triple therapy, every effort should be made to maintain the INR as close to 2.0 as possible, and the aspirin dose should be kept at < 100 mg. If bleeding persists, it is advised that aspirin be discontinued first, as clopidogrel seems to be more important than aspirin in preventing stent thrombosis after PCI.