Influence of timing of clopidogrel treatment on the efficacy and safety of bivalirudin in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention: an analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial

JACC Cardiovasc Interv. 2008 Dec;1(6):639-48. doi: 10.1016/j.jcin.2008.10.004.

Abstract

Objectives: This study sought to determine if the efficacy of bivalirudin alone versus heparin plus a glycoprotein (GP) IIb/IIIa inhibitor is dependent upon the duration of clopidogrel pre-treatment in patients undergoing percutaneous coronary intervention (PCI) in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.

Background: The administration of a clopidogrel loading dose several hours before PCI reduces the risk of periprocedural thrombotic events.

Methods: Patients with an acute coronary syndrome were randomized to heparin plus a GP IIb/IIIa inhibitor (control), bivalirudin plus a GP IIb/IIIa inhibitor, or bivalirudin alone. Dose and timing of clopidogrel were left to the investigator's discretion.

Results: Of 13,819 patients randomized, 7,789 underwent PCI. When clopidogrel was initiated at any time before angiography or within 30 min after PCI, randomization to bivalirudin alone (n = 2,284) or control (n = 2,189) was associated with similar ischemic outcomes (8.2% vs. 8.3%, risk ratio: 0.98, 95% confidence interval: 0.81 to 1.20). Those patients who received clopidogrel >30 min after PCI or not at all experienced an increase in ischemic events when randomized to bivalirudin alone (n = 290) versus control (n = 317) (14.1% vs. 8.5%, risk ratio: 1.66, 95% confidence interval: 1.05 to 2.63). Major bleeding was significantly less frequent in patients treated with bivalirudin alone.

Conclusions: This post-hoc analysis suggests that in acute coronary syndrome patients, as long as clopidogrel is administered before or within 30 min of PCI treatment with bivalirudin alone is similarly effective to heparin plus a GP IIb/IIIa inhibitor in suppressing 30-day ischemic events with significantly less bleeding. If it is anticipated that clopidogrel will be given late or not at all after PCI, bivalirudin alone may be associated with worse ischemic outcomes. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / diagnostic imaging
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Angioplasty, Balloon, Coronary* / mortality
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Clopidogrel
  • Coronary Angiography
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Hirudins / administration & dosage*
  • Hirudins / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / prevention & control
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / adverse effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Risk Assessment
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome
  • Troponin / blood
  • Young Adult

Substances

  • Anticoagulants
  • Hirudins
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • Troponin
  • Heparin
  • Clopidogrel
  • Ticlopidine
  • bivalirudin

Associated data

  • ClinicalTrials.gov/NCT00093158