Dangas G， Mehran R， Guagliumi G， Caixeta A， Witzenbichler B， Aoki J， Peruga JZ， Brodie BR， Dudek D， Kornowski R， Rabbani LE， Parise H， Stone GW; HORIZONS-AMI Trial Investigators.
    Columbia University Medical Center， New York， New York; Cardiovascular Research Foundation， New York， New York 10022， USA. gdangas@crf.org
Abstract
    OBJECTIVES: Our aim was to determine whether a 600-mg loading dose of clopidogrel compared with 300 mg results in improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
    BACKGROUND: A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation.
    METHODS: In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial， 3，602 patients with STEMI undergoing primary PCI were randomized to bivalirudin (n = 1，800) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (n = 1，802). Randomization was stratified by thienopyridine loading dose， which was determined before random assignment.
    RESULTS: Patients in the 600-mg (n = 2，158) compared with the 300-mg (n = 1，153) clopidogrel loading dose group had significantly lower 30-day unadjusted rates of mortality (1.9% vs. 3.1%， p = 0.03)， reinfarction (1.3% vs. 2.3%， p = 0.02)， and definite or probable stent thrombosis (1.7% vs. 2.8%， p = 0.04)， without higher bleeding rates. Compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor， bivalirudin monotherapy resulted in similar reductions in net adverse cardiac event rates within the 300-mg (15.2% vs. 12.3%) and 600-mg (10.4% vs. 7.3%) clopidogrel loading dose subgroups (p(interaction) = 0.41). By multivariable analysis， a 600-mg clopidogrel loading dose was an independent predictor of lower rates of 30-day major adverse cardiac events (hazard ratio: 0.72 [95% confidence interval: 0.53 to 0.98]， p = 0.04).
    CONCLUSIONS: In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens， a 600-mg loading dose of clopidogrel may safely reduce 30-day ischemic adverse event rates compared with a 300-mg loading dose. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction