November 23, 2010
myocardial infarction (STEMI). Although small-scaled studies have suggested beneficial effects of intracoronary (IC) over intravenous (IV) administration, it is uncertain whether this route is more effective. This trial investigated whether IC administration of abciximab is superior to IV administration in improving myocardial reperfusion in patients undergoing primary PCI with thrombus aspiration. Methods The CICERO trial, a single-center prospective randomized open-label trial with blinded evaluation of endpoints, randomized STEMI patients undergoing primary PCI with thrombus aspiration within 12 hours of symptom onset to either an IC or IV bolus of abciximab (0.25 mg/kg). Patients were pre-treated with aspirin, heparin, and clopidogrel. The primary endpoint was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution (STR). Secondary endpoints included myocardial reperfusion as assessed by myocardial blush grade (MBG), enzymatic infarct size defined by peak creatinine kinase (CK), myocardial band fraction of CK (CK-MB), and cardiac troponin T (cTnT), and major adverse cardiac events (MACE) at 30 days. Results A total of 534 patients (6413 years, 74% male, 12% diabetics, and 47% anterior infarctions) were randomized between September 2008 and April 2010. The incidence of complete STR was similar in the IC and IV groups (64% versus 62%, p0.562). However, the incidence of MBG 2/3 was higher in the IC group than in the IV group (76% versus 67%, p0.022). Furthermore, enzymatic infarct size was approximately 30% smaller in the IC than in the IV group (p0.008). The incidence of MACE was similar in both groups (5.5% versus 6.1%, p0.786). Conclusion In patients undergoing primary PCI with thrombus aspiration, IC administration of abciximab is not superior to IV in improving myocardial reperfusion as assessed by STR. However, IC administration is associated with improved myocardial reperfusion as assessed by MBG and a smaller enzymatic infarct size.
Chest tube drainage and blood product usage were determined over 24 hours. Cardiac marker release and ischemic event data will be analyzed. Results: There was no greater bleeding in the TEG-guided patients who underwent CABG earlier (2.5 / 1.7 days) than the recommended ACC/AHA guidelines. Red blood cells transfusion and chest tube drainage were not greater in the TEG-guided group of patients as compared to non-guided patients. In addition, CABG induced an immediate reduction in platelet counts and function (Table). Despite persistent low platelet count, platelet function rose to preoperative levels at 24 hrs post-CABG. Conclusions: This is the first prospective study to demonstrate that the timing of CABG can be optimized by an objective measurement of platelet function by TEG in clopidogrel treated patients. Patients on clopidogrel therapy can safely undergo earlier CABG than recommended by guidelines when the timing of the surgery is guided by TEG based platelet function measurement.
Author Disclosures: Y.L. Gu: None. M.A. Kampinga: None. W.G. Wieringa: None. M.L. Fokkema: None. A.F. van den Heuvel: None. E. Tan: None. G. Pundziute: None. R. van der Werf: None. S. Hoseyni Guyomi: None. F. Zijlstra: None. B.J. de Smet: None.
21757 A Randomized Placebo Controlled Trial of Intravenous Erythropoietin to Reduce Infarct Size After ST-Segment Elevation Myocardial Infarction: Primary Results of the REVEAL Trial
Sunil V Rao, Rakhi Kilaru, Thomas J Povsic, Chiara Melloni, Laura Melton, The Duke Clinical Rsch Institute, Durham, NC; Raymond J Kim, The Duke Cardiovascular Magnetic Resonance Cntr, Durham, NC; John Heitner, New York Methodist Hosp, New York, OH; Subha Raman, The Ohio State Univ Med Cntr, Columbus, OH; Gregory Barsness, Mayo Clinic, Rochester, MN; Luigi Ferrucci, Edward G Lakatta, The National Institute on Aging, Baltimore, MD; Robert A Harrington, The Duke Clinical Rsch Institute, Durham, NC; Samer S Najjar; Washington Hosp Cntr, Washington, DC
Background: Acute myocardial infarction is a leading cause of morbidity and mortality. Preclinical studies have demonstrated that Erythropoietin exerts an important cytoprotective effect in experimental models of myocardial injury. We evaluated the safety and efficacy of a single infusion of epoetin alfa in patients with ST-elevation myocardial infarctions (STEMI). Methods and Results: 136 Patients with STEMI who underwent successful percutaneous coronary intervention (PCI) within 8 hours of symptom onset were randomized to 60,000 units of intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. The primary endpoint was infarct size assessed by cardiac magnetic resonance (CMR) imaging study 2–6 days after study medication administration. Secondary endpoints included infarct size by CMR at 3 months as well as death, recurrent MI, unplanned PCI, and arterial or venous thrombotic events. Infarct size did not differ between the 2 groups at either the early (15.810.3% vs. 15.010.0%, pNS) or late time points (10.68.6% vs. 10.47.6%, pNS). In pre-specified analyses of patients over the age of 70 years (N21) infarct size within the first week was larger in the epoetin alfa than in the placebo group (19.99.9% 11.77.2%, p0.02). Patients who received epoetin alfa had a higher incidence of death, myocardial infarction, stroke or stent thrombosis (4% vs. 0%, p0.04). Conclusions: A single infusion of epoetin alfa in patients with STEMI who were successfully reperfused did not reduce infarct size, and may increase infarct size and major adverse cardiac events in older patients.
Author Disclosures: S.V. Rao: None. R. Kilaru: None. T.J. Povsic: None. C. Melloni: None. L. Melton: None. R.J. Kim: Ownership Interest; Modest; Heart IT Technologies. J. Heitner: None. S. Raman: None. G. Barsness: None. L. Ferrucci: None. E.G. Lakatta: None. R.A. Harrington: None. S.S. Najjar: None.
21842 Time-BAsed StRateGy to REduce Clopidogrel AssociaTed Bleeding DuRing CABG. Results From the TARGET CABG Study
Elisabeth Mahla, Mark Antonino, Thomas Suarez, Kevin P Bliden, Alex Sequeria, Peter Chow, Udaya Tantry, Paul A Gurbel; Sinai Hosp Baltimore, Baltimore, MD
Background: Guidelines recommend withholding clopidogrel for 5 7 days before CABG to reduce bleeding. Since clopidogrel therapy is associated with wide response variability, we measured ADP-induced platelet-fibrin clot-strength (PFCS) by Thrombelastography (TEG) to determine when to perform CABG and hypothesized that there would be no difference in bleeding rates compared to clopidogrel naı¨ve (CN) patients. Methods: Based on admission PFCS levels, patients underwent CABG after prespecified waiting periods of (a) no delay (non-responders:50 mm 2uM ADP-PFCS), (b) 3 days (semi responders:35–50 mm 2uM ADP-PFCS) and (c) 5 days (responders: 35 mm 2 uM ADP-PFCS). Platelet count and function were determined [n200 patients, data on 140 patients were available (CN90 pts and TEG-Guided50 pts)] on admission, immediate pre-and post-CABG, and 24 hrs post-CABG.
Author Disclosures: E. Mahla: None. M. Antonino: None. T. Suarez: None. K.P. Bliden: None. A. Sequeria: None. P. Chow: None. U. Tantry: None. P.A. Gurbel: Research Grant; Significant; Sanofi Aventis, Astra Zeneca, Daichi,. Speakers Bureau; Significant; Astar Zeneca, Eli Lilly, Bayer, Schering Plough. Honoraria; Significant; Astar Zeneca, Eli Lilly, Bayer, Schering Plough. Consultant/Advisory Board; Significant; Astar Zeneca, Eli Lilly, Bayer, Schering Plough.
The Results of the ASCET Trial
Alf-Aage Pettersen, Ingebjorg Seljeflot, Dept of Cardiology, Oslo Univ Hosp, Ullevaal, Oslo, Norway; Michael H Abdelnoor, Cntr for Clinical Rsch, Oslo Univ Hosp, Ullevaal, Oslo, Norway; Harald Arnesen; Dept of Cardiology, Oslo Univ Hosp, Ullevaal, Oslo, Norway
Background: Patients with coronary artery disease (CAD) on single antiplatelet therapy still have a high risk for atherothrombotic events. Aspirin non-responsiveness has been discussed as a risk factor for thromboembolic events. There is a need for validated tools that can identify patients with a high on-treatment residual platelet reactivity (RPR) as a guide to change or intensify antiplatelet treatment. Aims and methods: The ASCET study is the first prospective, randomized trial aimed to investigate the relation of platelet function tests to clinical outcome in patients with symptomatic, stable CAD on single antiplatelet therapy. Patients (n1001) with stable CAD, all verified with coronary angiography and on aspirin 160 mg/d, were randomized to continue treatment with aspirin 160 mg/d or clopidogrel 75 mg/d. Platelet function was assessed at randomization with the PFA100 method and platelet aggregometry. Compliance was assessed by determination of serum thromboxane B2. The patients were followed up for two years. The primary end-point was a composite of all-cause death, non-fatal myocardial infarction, ischemic stroke and unstable angina. Major and minor bleedings were registered. Results: The total number of primary endpoint was 106. No difference in event rates between the randomized groups was observed (56/503 on aspirin, 50/498 on clopidogrel, p0.57). The prevalence of RPR with the PFA100 method (aspirin non-responders) was 26% at randomiza- tion, when compliance to aspirin medication was excellent. After randomization, high on-treatment RPR in the aspirin group evaluated with PFA100 did not influence on the primary endpoint (13.1% vs 10.5%, p0.41). Platelet aggregometry measures with arachidonic acid (AA) did also not predict clinical outcome. Aspirin non-responders randomized to clopidogrel had a non-significant reduction in the combined endpoint compared to aspirin non-responders randomized to continued aspirin treatment (7.8% vs 13.1%, p0.16). Conclusion: Response to aspirin treatment evaluated with the PFA100 method and platelet aggregometry with AA did