Multicenter Registry of High-Risk Percutaneous Coronary Intervention and Adequate Platelet Inhibition - MR PCI
The goal of the trial was to evaluate the effect on inhibition of platelet aggregation (IPA) of four antiplatelet regimens of different combinations of glycoprotein (GP) IIb/IIIa inhibitors and clopidogrel among patients undergoing elective, high-risk percutaneous coronary intervention (PCI).
Patients Enrolled: 120
Mean Follow Up: 30 days
Use of chronic antiplatelet therapy (aspirin daily, clopidogrel >5 days or total dose of >300 mg >24 hours) and severe coronary artery disease amenable to PCI with ≥1 of the following clinical criteria: prior stroke, prior peripheral vascular disease, diabetes, documented microalbuminuria, prior MI, or presence of unstable angina with electrocardiogram changes or elevated cardiac enzymes consistent with MI
ST-segment elevation MI, history of bleeding diathesis, stroke within 3 months, chronic total occlusion/angiographically visible thrombus, alcohol abuse, prothrombin time >1.5 times control, platelet count <100,000/mm3, creatinine >4.0 mg/dl, and hematocrit <30%
IPA assessed at 10 minutes, 6-8 hours, and 24 hours
Degree of platelet inhibition at 10 minutes; in-hospital and 30-day MACE, which included death, MI, and need for urgent target vessel revascularization; TIMI major and minor bleeding in-hospital
Patients were randomized in an open-label manner at three hospitals in India to tirofiban (n = 30), eptifibatide (n = 30), tirofiban + clopidogrel 600 mg loading dose (n = 30), or eptifibatide + clopidogrel 600 mg loading dose (n = 30). Tirofiban dose was 25 µg/kg bolus followed by an infusion of 0.15 µg/kg/min for 6-8 hours post-PCI.
Eptifibatide dose was a double bolus of 180 µg/kg followed by 2 µg/kg/min infusion for 6-8 hours. IPA was measured at baseline, 10 minutes, 6-8 hours, and 24 hours.
Post-PCI clopidogrel 75 mg daily for at least 30 days and aspirin indefinitely
At study entry, 35% of patients had diabetes, 56% had unstable angina, and 50% had a prior myocardial infarction (MI). IPA at 10 minutes post-bolus was higher with tirofiban than eptifibatide, both without (95.7% vs. 89.4%, p = 0.003) or with the clopidogrel 600 mg load (96.1% vs. 92.9%, p = 0.003). Achievement of >95% IPA was highest in the tirofiban + clopidogrel group, followed by the tirofiban alone group, the eptifibatide + clopidogrel group, and the eptifibatide alone group (73.3%, 63.3%, 40%, and 36.7%, respectively, p < 0.001).
Results were similar at 6-8 hours, with higher IPA with tirofiban than eptifibatide, both without (91.9% vs. 84.8%, p < 0.001) or with the clopidogrel 600 mg load (94.2% vs. 86.1%, p < 0.001). By 24 hours, the clopidogrel loading groups had higher IPAs than the GP IIb/IIIa inhibitor groups alone, without a difference between GP IIb/IIIa groups (28.3% for tirofiban + clopidogrel vs. 31.1% for eptifibatide + clopidogrel, p = 0.11; 12.1% for tirofiban vs. 11.1% for eptifibatide, p = 0.11).
There were no in-hospital bleeding events in the clopidogrel loading groups, one major bleed in the tirofiban alone group, and one minor bleed in the eptifibatide alone group. Major adverse cardiac events (MACE) occurred in 6.6% of the tirofiban + clopidogrel group, 0% of the eptifibatide + clopidogrel group, and 3.3% of both the tirofiban alone group and the eptifibatide alone group.
Among patients undergoing elective, high-risk PCI, high-dose tirofiban with or without a 600 mg load of clopidogrel was associated with higher rates of IPA at 10 minutes and 6-8 hours compared with eptifibatide with or without a 600 mg load of clopidogrel. High clopidogrel loading dose was not associated with a difference in IPA early, but was associated with higher IPAs at 24 hours compared with no loading dose.
While statistically significant differences in IPA levels were observed between groups, it is not known what clinical impact a difference of ~5% in IPA would have on outcomes. It should be noted that the dose of both tirofiban and eptifibatide used in the study differ from the approved doses. The tirofiban bolus was higher and infusions for both GP IIb/IIIa inhibitors was shorter at only 6-8 hours. All patients were pretreated with clopidogrel per the inclusion criteria; results should not be extrapolated to high-risk PCI patients not pretreated with clopidogrel and aspirin. Bleeding was low in all four arms of the trial, but the sample size was small and was not powered to detect a difference in bleeding between groups.
Mardikar HM, Hiremath MS, Moliterno DJ, et al. Optimal platelet inhibition in patients undergoing PCI: data from the Multicenter Registry of High-Risk Percutaneous Coronary Intervention and Adequate Platelet Inhibition (MR PCI) study. Am Heart J 2007;154:344.e1-5.
Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Ticlopidine, Fibrinolytic Agents, Electrocardiography, Peripheral Vascular Diseases, Purinergic P2Y Receptor Antagonists, Tyrosine, Percutaneous Coronary Intervention, Peptides, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex
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