Problem Acute MI
Format Double-blinded multi-center RCT
Treatment Bivalirudin (vs. UFH/GpIIbIIIa) & DES (vs. BMS)
Control Nil
Population 3602 patients (1800 bivalirudin alone, 1802 UFH plus GP IIb/IIIa inhibitors)
Inclusion criteria Consecutive patients 18 years of age or older who presented within 12 hours after the onset of symptoms and who had ST-segment elevation of 1 mm or more in two or more contiguous leads, new left bundle-branch block, or true posterior myocardial infarction were considered for enrollment.
Exclusion criteria The principal exclusion criteria were contraindications to the study medications; prior administration of thrombolytic agents, bivalirudin, glycoprotein IIb/IIIa inhibitors, low-molecular-weight heparin, or fondaparinux for the present admission (although prior unfractionated heparin was allowed); current use of warfarin; history of bleeding diathesis, coagulopathy, heparin-induced thrombocytopenia, intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; stroke or transient ischemic attack within the previous 6 months or any permanent neurologic deficit; refusal to receive blood transfusions; gastrointestinal or genitourinary bleeding within the previous 2 months; major surgery within the previous 6 weeks; a known platelet count of less than 100,000 cells per cubic millimeter or a hemoglobin level of less than 10 g per deciliter, a planned elective surgical procedure that would necessitate an interruption in treatment with thienopyridines during the first 6 months after enrollment; coronary stent implantation within the previous 30 days; and noncardiac coexisting conditions that could limit life expectancy to less than 1 year or that might interfere with compliance with the protocol.
Follow-up 3 years (ongoing)
Primary endpoint Two primary 30-day end points were prespecified: major bleeding (not related to coronary-artery bypass grafting) and combined adverse clinical events, defined as the combination of major bleeding or a composite of major adverse cardiovascular events, including death, reinfarction, target-vessel revascularization for ischemia, and stroke (hereinafter referred to as net adverse clinical events).

Major bleeding was defined as intracranial or intraocular hemorrhage; bleeding at the access site, with a hematoma that was 5 cm or larger or that required intervention; a decrease in the hemoglobin level of 4 g per deciliter or more without an overt bleeding source or 3 g per deciliter or more with an overt bleeding source; reoperation for bleeding; or blood transfusion.

Bleeding was also assessed and adjudicated on the basis of the Thrombolysis in Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scales. Major adverse cardiovascular events have been defined previously.

Death from cardiac causes was defined as death due to acute myocardial infarction, cardiac perforation or pericardial tamponade, arrhythmia or conduction abnormality, stroke, procedural complications, or any death for which a cardiac cause could not be ruled out.

Death from noncardiac causes included bleeding-related death. Stent thrombosis was defined as the definite or probable occurrence of a stent-related thrombotic event according to the Academic Research Consortium classification.
Secondary endpoint(s) .
Details To determine the safety and efficacy of bivalirudin alone compared to unfractionated heparin (UFH) plus routine GP IIb/IIIa inhibitors, and those of the paclitaxel-eluting Taxus stent compared to a bare-metal Express stent in patients with AMI undergoing primary PCI

Randomised 2x2 factorial trial
Brief summary: Bivalirudin safer than UFH&GPiibiia in STEMI for PCI; Less revasc for DES vs. BMS
PAPER: Bivalirudin during primary PCI in acute myocardial infarction.
Date 22 May 2008
Journal N Engl J Med. 2008 May 22;358(21):2218-30.
Information Bivalirudin (vs. UFH & abciximab) in STEMI @ 30d
--Net adverse clinical events (RR 0.76; p=0.005)
--Major bleeding (RR 0.60; p=0.001)
--Death from cardiac (RR 0.62; p=0.03) & all (RR 0.66; p=0.047)
-No difference in MACE
-No difference in stent thrombosis (@ 30d)
--Increased thrombosis for bivalirudin within 24hrs (p=0.001)
--Offset by a reduction between 24hrs and 30days
PAPER: Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial.
Date 3 Oct 2009
Journal Lancet. 2009 Oct 3;374(9696):1149-59.
Information Bivalirudin (vs. UFH & abciximab) in STEMI @ 1yr
-Lower rate of net adverse cardiac events (HR 0.83; p=0.022)
--Largely due to significantly lower bleeding (HR 0.61; p=0.0001)
-Similar rate of MACE (HR 1.00; p=0.98)
PAPER: Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction.
Date 7 May 2009
Journal N Engl J Med. 2009 May 7;360(19):1946-59.
Information Piclataxel (n=2257) vs. BMS (n=749) @ 1yr
-Significantly reduced ischaemia-driven revasc (0.59; p=0.002)
-Similar rates of death, reinfarction, stroke and stent thrombosis (HR 1.02; p=0.92)
PAPER: Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results
Date 25 Jun 2011
Journal Lancet. 2011 Jun 25;377(9784):2193-204.
Information Bivalirudin (vs. UFH & abciximab) in STEMI @ 3yr
-Lower rates of ACM, cardiac mortality, reinfarction and major bleeding
-No significant difference in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events

Paclitaxel-eluting stent (vs. BMS) @ 3yr
-Lower rates of ischaemia-driven target lesion revascularisation
-No significant differences in the rate of death, reinfarction, stroke or stent thrombosis
-Stent thrombosis was high (≥4·5%) in both groups