ACUITY: The Acute Catheterization and Urgent Intervention Triage StrategY Trial: The PCI Subanalysis

• Summary|
• Trial Design|
• Clinical Outcomes

Summary of Results

• ACUITY is the largest clinical trial to evaluate Angiomax^® (bivalirudin) in patients with moderate- and high-risk Unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) undergoing an early invasive strategy (N=13,819) ¹
• At baseline 76% of the percutaneous coronary intervention (PCI) patient population had elevated cardiac biomarkers or ST-segment deviation²
• 27% of the PCI population had a history of diabetes
• Results in PCI patients were consistent with Randomized Evaluation of PCI Linking ANGIOMAX to Reduced Clinical Events (REPLACE-2) and overall ACUITY trial results²*
  • ANGIOMAX alone (n=2,619) demonstrated similar ischemic efficacy versus heparin(s) + glycoprotein (GP) IIb/IIIa (n= 2,561) (8.8% vs. 8.2%, respectively; P = .45)
  • Net clinical outcome with ANGIOMAX vs heparin(s) + GP IIb/IIIa was 11.6% vs. 13.3%, respectively (P = .057)
  • Major bleeding^¶ with ANGIOMAX vs heparin(s) + GP IIb/IIIa was 3.5% vs 6.8%, respectively (P < .001)²
• Results in the ANGIOMAX + GP IIb/IIIa inhibitor arm (n=2,609) vs heparin(s) + GP IIb/IIIa inhibitor were similar for net clinical outcome, composite ischemia, and major bleed^2†
• At 1 year, mortality rates in the 2 treatment groups in the ACUITY PCI subset were comparable (3.1% for ANGIOMAX alone; 3.2% for heparin(s) + GP IIb/IIIa inhibitor; P = .76), which demonstrated consistent long-term efficacy of ANGIOMAX treatment.^2,3

* The safety and effectiveness of ANGIOMAX have not been established in patients with acute coronary syndromes (ACS) who are not undergoing PCI.^4
† Major bleed:¹ Defined in ACUITY as non-CABG intracranial, retroperitoneal, or intraocular bleeding; access-site hemorrhage requiring intervention; ≥5 cm diameter hematoma; reduction in hemoglobin concentration of ≥4 g/dL without an overt source of bleeding; reduction in hemoglobin concentration of ≥3 g/dL with an overt source of bleeding; reoperation for bleeding; use of any blood product transfusion.
^¶ Please see important safety information and bleeding definitions.

Trial Design

Results in UA/NSTEMI patients undergoing PCI in ACUITY are consistent with REPLACE-2 findings

• Demonstrated in ACUITY, the largest clinical trial to evaluate ANGIOMAX in patients with moderate- and high-risk ACS undergoing an early invasive strategy (N=13,819)¹
• 76% of the PCI patient population had elevated cardiac biomarkers or ST-segment deviation²
• Results in PCI patients were consistent with overall trial results²*

CABG=coronary artery bypass grafting.
* The safety and effectiveness of ANGIOMAX have not been established in patients with ACS who are not undergoing PCI.^4
† Stratified by preangiography thienopyridines use or administration.
^‡ unfractionated heparin (UFH) or enoxaparin.
^§ ANGIOMAX monotherapy (with GP IIb/IIIa inhibition reserved for severe breakthrough ischemia and procedural complications during PCI).

Inclusion Criteria^1,5

• Age ≥18 years
• Chest pain ≥10 min within 24 h
• At least one of:
  • New ST-segment depression or transient elevation ≥1 mm
  • troponin I, T, or CKMB
  • Documented coronary artery disease
  • Presence of all 4 UA risk criteria
    • Age ≥65 years
    • Aspirin within the last 7 days
    • ≥2 angina episodes within 24 h
    • ≥3 cardiac risk factors: hypertension, hypercholesterolemia, family history of coronary artery disease, diabetes, smoking
• Written informed consent

Major Exclusion Criteria^1,5

• No angiography within 72 h
• Acute ST-segment elevation myocardial infarction (STEMI) or shock
• Bleeding diathesis or major bleed within 2 weeks
• Platelet count <100,000/mm³
• INR >1.5 times control
• CrCl <30 mL/min
• Abciximab or ≥2 prior LMWH doses
  • Prior UFH, LMWH (1 dose), eptifibatide and tirofiban were allowed
• Allergy to study drugs, contrast dye

CKMB = creatine kinase-MB; CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-molecular-weight heparin; STEMI = ST-segment elevation myocardial infarction; UFH = unfractionated heparin.

Clinical End Points

• Net clinical outcome
  • Death, myocardial infarction (MI), unplanned revascularization for ischemia or non-CABG major bleeding
• Composite ischemia
  • Death, MI, or unplanned revascularization for ischemia
• Non-coronary artery bypass grafting (Non-CABG) major bleeding
  • Intracranial, intraocular, or retroperitoneal bleeding
  • Access site bleed requiring intervention/surgery
  • Hematoma ≥5 cm
  • Hemoglobin (Hgb) ≥4 g/dL without an overt source
  • Hgb ≥3 g/dL with an overt source
  • Reoperation for bleeding
  • Any blood transfusions

Baseline Characteristics in PCI Subpopulation²

P= Not significant for all values.

Baseline High-Risk Features²

Clinical Outcomes

30-day results for ACUITY PCI subset^1,2,6

Heparin(s) = UFH or enoxaparin
^† Important Bleeding Definitions
^¶ IN THE ACUITY ANGIOMAX-ALONE GROUP: 91% of PCI patients received ANGIOMAX monotherapy.¹

• Results in the ANGIOMAX + GP llb/llla arm (n = 2,609) vs heparin(s) + GP IIb/IIIa²
  
  —Net clinical outcome was 14.9% vs 13.3% (P = .10)
  —Composite ischemia was 9.3% vs 8.2% (P = .16)
  —Major bleed was 7.5% vs 6.8% (P = .32)

ACUITY PCI subset mortality results at 1 year confirm long-term efficacy³

^¶ In the ACUITY ANGIOMAX-ALONE GROUP: 91% of PCI patients received ANGIOMAX monotherapy.^2
§ Mortality rates based on 1-year Kaplan-Meier estimates.³