Optimal Platelet Inhibition in Patients Undergoing PCI; Data From MR PCI
Background: Optimal inhibition of platelet aggregation (IPA) may afford greater protection against ischemic events during percutaneous coronary intervention (PCI). The objective of this study was to test several antiplatelet regimens in elective high-risk PCI patients by comparing different combinations of glycoprotein IIb/IIIa inhibitors and clopidogrel.
Methods: The study was a randomized open-label study at 3 heart centers in India. One hundred twenty patients were enrolled between July 2006 and September 2006. Patients were randomized to 1 of the 4 groups: group A -- tirofiban, group B -- eptifibatide, group C -- tirofiban + clopidogrel 600-mg loading dose, and group D -- eptifibatide + clopidogrel 600-mg loading dose. All patients received a clopidogrel maintenance dose after PCI. The primary outcome measure was the IPA assessed at 10 minutes, at 6 to 8 hours, and at 24 hours.
Results: The IPA was higher with high-dose tirofiban compared with eptifibatide at 10 minutes (95.88 ± 5.85% vs 91.22 ± 7.52%, P = .003) and at 6 to 8 hours (93.11 ± 7.6% vs 85.45 ± 11.03, P < .001). Significantly more patients achieved >95% IPA with the high-dose tirofiban regimen.
Conclusions: This head-to-head study comparing high-dose tirofiban with double-bolus eptifibatide demonstrated higher degree of platelet inhibition with high-dose tirofiban at 10 minutes and at 6 to 8 hours in patients undergoing elective high-risk PCI. The addition of clopidogrel did not acutely extend the IPA from intravenous glycoprotein IIb/IIIa inhibitors, but did so at 24 hours.

Over the last decade, a vast amount of information has confirmed the central role of platelets in acute coronary syndromes (ACS) and complications after high-risk percutaneous coronary intervention (PCI). This has prompted the development of aggressive antiplatelet regimens particularly for ACS patients undergoing PCI. Many recent trials have used different dosing, timing of administration, and combinations of antiplatelet agents with the intention of achieving greater antithrombotic protection. Dual antiplatelet therapy with aspirin and clopidogrel has become a cornerstone in clinical practice guidelines for patients undergoing PCI with stenting., Another class of antiplatelet drugs that have shown consistent benefit in ACS-PCI is the glycoprotein (GP) IIb/IIIa antagonists. Currently, GP IIb/IIIa antagonists are considered the most specific and potent inhibitors of platelet aggregation in acute thrombosis. The GP IIb/IIIa antagonists, eptifibatide and tirofiban, have been approved for the treatment of patients with ACS who are undergoing PCI.

The results from recent studies suggest that a more vigorous approach to the inhibition of platelet aggregation (IPA) may afford greater protection against ischemic events. It remains to be seen if high clopidogrel loading (600 mg) further reduces ischemic events in patients who are already receiving aspirin and clopidogrel. If it does, this information will be particularly useful in optimizing the antiplatelet strategy among patients who receive pretreatment with clopidogrel for several days before intervention. The MR PCI study was performed to define optimal antiplatelet therapy in high-risk patients undergoing PCI. The primary objective was to compare high-dose tirofiban with double-bolus eptifibatide regarding the extent of platelet inhibition. A secondary aim was to evaluate the efficacy of 600-mg loading clopidogrel dose during PCI in reducing the inhospital and 30-day adverse outcome in ACS patients.