Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty With Stent Implantation With Either a Slow Rate-release Paclitaxel-eluting Stent (TAXUS™) or Uncoated Bare Metal Stent (EXPRESS2™)

The primary objectives of the trial are:

1. To establish the safety and efficacy of the use of bivalirudin (+ bail-out GP IIb/IIIa inhibitors) compared to the use of unfractionated heparin + GP IIb/IIIa inhibitors in patients with acute myocardial infarction undergoing a primary angioplasty strategy.
2. To establish the safety and efficacy of the slow rate release paclitaxel-eluting TAXUS™ stent compared to an otherwise identical uncoated bare metal EXPRESS2™ stent.

Prospective, 2 x 2 factorial single blind, randomized, multi-center trial of 3400 patients enrolled at up to 200 centers. Patients will be randomized 1:1 in the emergency room to a) anticoagulation with unfractionated heparin plus routine GP IIb/IIIa inhibition vs. b) bivalirudin and bail-out GP IIb/IIIa inhibition. Following angiography, patients with lesions eligible for stenting will then undergo a second randomization (3:1) to stent implantation with either a) a slow rate-release paclitaxel-eluting stent (TAXUS™) or b) an otherwise identical uncoated bare metal stent (EXPRESS2™).

Inclusion Criteria:

• Must have clinical symptoms consistent with AMI (e.g., angina or anginal equivalent)lasting >20 minutes but <12 hours in duration;
• ST-segment elevation of >1 mm in >2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of >1 mm in >2 contiguous anterior leads;
• The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent.

Exclusion Criteria:

• The patient has a known hypersensitivity or contraindication to any of the following medications:

  • Heparin, pork or pork products
  • Both abciximab and eptifibatide
  • Aspirin
  • Both Clopidogrel and Ticlopidine
  • Bivalirudin
  • Paclitaxel or Taxol
  • The polymer components of the TAXUS™ stent (SIBS)
  • Stainless steel and/or
  • Contrast media;

• Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa inhibitors, low molecular weight heparin or fondaparinux for this admission. Patients receiving prior unfractionated heparin may be enrolled, and treated per randomization;

• Current use of coumadin;

• Systemic (intravenous) Paclitaxel or Taxol use within 12 months;

• Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study;

• History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions;

• History of intra-cerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke;

• Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect;

• Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks;

• Recent history or known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL;

• Extensive peripheral vascular disease, such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated;

• An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first six months post enrollment;

• Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance;

• Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period;

• Previous enrollment in this trial;

• Patients who underwent coronary stent implantation within the past 30 days.