Randomized Trial to Evaluate the Relative Protection Against Post-PCI Microvascular Dysfunction and Post-PCA Ischemia Among Anti-Platelet and Anti-Thrombotic Agents - PROTECT - TIMI 30
The goal of the study was to evaluate the efficacy and safety of the combination of reduced dose antithrombin and glycoprotein IIb/IIIa inhibitor compared to a direct thrombin inhibitor alone among high-risk patients with unstable angina or non-ST elevation myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI).
Patients Enrolled: 857
Mean Follow Up: 48 hours
Mean Patient Age: Mean age 60 years
PCI of a native vessel in patients with unstable angina or non-ST elevation MI plus one of the following risk factors: diabetes, troponin positive, ST depression ≥0.5 mm, or TIMI risk score of ≥3
Efficacy: Coronary flow reserve postadenosine, which is the ratio of the TIMI frame count preadenosine/TIMI frame count postadenosine
Safety: TIMI major bleed
Death, MI, or ischemic event by 48 hours; duration of ischemia on Holter at 24 hours; and rise in troponin post-PCI
Patients were consented prior to angiography and randomized 1:1:1 during angiography to either eptifibatide plus low-dose unfractionated heparin (50 U/kg bolus plus infusion to target activated clotting time 200-250), eptifibatide plus low-dose enoxaparin (0.5 mg/kg infusion), or bivalirudin (0.75 mg/kg bolus plus 1.75 mg/kg/h infusion) (n = 284). Eptifibatide (n = 573) was dosed at 180/180 µg/kg bolus plus 2 µg/kg/min infusion for 18-24 hours. Randomization was stratified by clopidogrel pretreatment >6 hours and ≤6 hours.
Aspirin and clopidogrel (300 mg prior to PCI and 75 mg/day thereafter)
Baseline characteristics were similar between treatment groups, with the exception of a slightly higher frequency of diabetes in the bivalirudin group (44% vs. 36%, p = 0.026). The population was high-risk as intended, with 54% troponin positive at enrollment, 29% with ST depression, and 55% with dyslipidemia.
In an analysis of patients with open arteries post-PCI, coronary flow reserve was higher in the bivalirudin group compared with the eptifibatide group (1.43 vs. 1.33, p = 0.036), but the difference was not significant when all patients were included (p = 0.13).
Thrombolysis in Myocardial Infarction (TIMI) frame count post-adenosine was 14.0 frames in each group (p = NS). TIMI myocardial perfusion grade (TMPG) 3 was more frequent in the eptifibatide group (57.9% vs. 50.9%, odds ratio [OR] 1.44, p = 0.048) after adjustment for baseline TMPG.
Duration of ischemia in patients who had an ischemic event by 24 hours was shorter in the eptifibatide group (36 minutes vs. 169 minutes, p = 0.013). Death, MI, or ischemic event by 48 hours trended lower in the eptifibatide group (14.2% vs. 18.0%, p = 0.15), as did death or MI (6.6% vs. 8.8%, p = 0.25). Median peak rise in troponin I post-PCI was 0.11 ng/ml in the eptifibatide group versus 0.21 ng/ml in the bivalirudin group (p = 0.24).
The primary safety endpoint of TIMI major hemorrhage was not significantly different between groups (0.7% for eptifibatide vs. 0% for bivalirudin, p = 0.308). All of the major bleeding events occurred in the eptifibatide plus enoxaparin group, with none in the eptifibatide plus unfractionated heparin group. TIMI minor hemorrhage was higher in the eptifibatide group (2.5% vs. 0.4%, p = 0.027), as were transfusions (4.4% vs. 0.4%, p < 0.001).
Among high-risk patients with unstable angina or non-ST elevation MI undergoing PCI, treatment with eptifibatide was associated with an improvement in myocardial perfusion, reduction in the duration of post-PCI ischemia, and trends toward reductions in clinical events and myonecrosis, but these benefits came at the expense of an increase in nonfatal bleeding.
Gibson CM, Morrow DA, Murphy SA, et al. A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: the PROTECT-TIMI-30 trial. J Am Coll Cardiol 2006;47:2364-73.
Presented by Dr. C. Michael Gibson at the Texas Heart Symposium, November 2004, New Orleans, LA.
Keywords: Depression, Odds Ratio, Myocardial Infarction, Platelet Aggregation Inhibitors, Heparin, Ticlopidine, Risk Factors, Hirudins, Percutaneous Coronary Intervention, Dyslipidemias, Troponin I, Enoxaparin, Recombinant Proteins, Peptide Fragments, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex
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