Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes (ACS)
Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes (ACS)
The purpose of this study is to show that, when compared with heparin (enoxaparin or
 unfractionated heparin) and routine GPIIb/IIIa inhibition (either started upfront or at the
 time of percutaneous coronary intervention [PCI]; Arm A):

 1. Bivalirudin with routine GPIIb/IIIa inhibition (either started upfront or at the time of
 PCI; Arm B) provides non-inferior or superior overall clinical outcomes and

 2. Bivalirudin alone (Arm C) reduces clinically significant bleeding. An important
 secondary objective for this comparison is to show that bivalirudin is not inferior for
 ischemic complications.
Inclusion Criteria:

 1. Be aged >=18 years at the time of randomization.

 2. Have symptoms which include at least 10 minutes of angina or anginal equivalent that
 the investigator believes has a high likelihood of being ischemic in origin within the
 24 hours prior to randomization consistent with a diagnosis of Unstable Angina/Non-ST
 Elevation Myocardial Infarction (UA/NSTEMI) (patients with symptoms atypical for
 cardiac ischemia should not be enrolled).

 3. Meet at least one of the following criteria for UA/NSTEMI:

 1. All of the following four features: *Age >= to 65 years; *aspirin taken within
 the last 7 days; *two or more episodes of angina in the last 24 hours; *three or
 more of the following risk factors: hypertension, high cholesterol, family
 history, diabetes, current smoker OR

 2. ECG changes: New or presumably new ST-segment depression >=0.1 MV (>=1mm), or
 transient (<30 minutes) ST-segment elevation >=0.1MV (>=1mm) in at least 2
 contiguous leads, OR

 3. Abnormal cardiac enzymes within the 24 hours before enrollment defined as
 elevated troponin I, T or creatine phosphokinase-MB isoenzyme (CPK-MB) level
 greater than the site's upper limit of normal (ULN) OR

 4. History of coronary artery disease with documentation of one of the following:
 *prior angiography (coronary stenosis of >50%); *prior PCI or Coronary Artery
 Bypass Grafting (CABG); *prior definite, documented myocardial infarction.

 4. Provide written informed consent before initiation of any study related procedures.

 Exclusion Criteria:

 1. Anticipated inability to perform angiography within 72 hours of randomization and
 anticipated inability to perform any intervention required (PCI or CABG) within the
 index hospitalization.

 2. ST segment elevation of >1 mm in 2 contiguous ECG leads lasting for >30 minutes, or
 new left bundle branch block, or a clinical syndrome consistent with acute evolving
 transmural MI requiring immediate thrombolytic or interventional reperfusion therapy.

 3. Cardiogenic shock (systolic blood pressure <80 mmHg for >30 minutes not responding to
 intravenous fluids, or requiring intravenous pressor agents or an intra-aortic balloon
 pump).

 4. Bleeding diathesis or any history of hemorrhagic stroke or other intra-cerebral bleed,
 cerebral arteriovenous malformation, cerebral aneurysm or prior ischemic stroke within
 the last 2 years, or any prior stroke with residual neurologic deficit.
 Gastrointestinal or genitourinary bleeding within the last 2-weeks.

 5. Platelet count <100,000 cells/mm3 at baseline, or history of heparin induced
 thrombocytopenia

 6. Patients on warfarin or phenprocoumon, unless they can be safely discontinued and the
 baseline INR is < 1.5 times control.

 7. Allergy to pork or pork products.

 8. Patients who have been started on and received 2 or more doses of low molecular weight
 heparin for the current admission prior to randomization (patients who have received
 one dose of low molecular weight heparin may still be enrolled.

 9. Patients who have been started on bivalirudin in the 6 hours prior to randomization

 10. Thrombolytic therapy or abciximab use within the last 24 hours.

 11. Treatment with a GPIIb/IIIa inhibitor at the time of randomization, which cannot be
 discontinued.

 12. Patients on Arixtra (fondaparinux).

 13. Absolute contraindication or allergy to:

 -  any one of enoxaparin, unfractionated heparin, bivalirudin or aspirin

 -  both abciximab and eptifibatide

 -  both eptifibatide and tirofiban

 -  iodinated contrast which cannot be pre-medicated

 14. Contraindications to angiography, including but not limited to severe peripheral
 vascular disease.

 15. Angina from secondary causes.

 16. Pregnancy or nursing mothers. Women of child bearing potential must have a negative
 urine or serum pregnancy test prior to enrollment.

 17. Calculated serum creatinine clearance < 30 mL/min (Determined by the Cockcroft Gault
 formula: ((140-age in yrs) x weight in kg)/(814.464 x Creatinine in mmol/l) or /(72 x
 [Creatinine in mg/dL]). For women, multiply by 0.85.

 18. Previous enrollment in this study.

 19. Patients currently enrolled in another investigational drug study that has not
 completed the follow-up phase.