Use of Clopidogrel Loading, Enoxaparin, and Double-Bolus Eptifibatide in the Setting of Early Percutaneous Coronary Intervention

In recent years, many changes in antithrombotic regimens and therapies in the settings of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) have been realized. These therapies include the use of glycoprotein IIb/IIIa platelet receptor inhibitors, adenosine diphosphate (ADP) inhibitors and low molecular weight heparins (LMWH), often in combination. Glycoprotein IIb/IIIa platelet receptor inhibitors are almost routinely used for PCI. Abciximab and eptifibatide have both demonstrated a reduction in adverse coronary events among patients undergoing coronary interventions.1–4 Eptifibatide is also effective in reducing the incidence of death and myocardial infarction in patients with non-ST segment elevation acute coronary syndromes.5 ADP platelet inhibitors, when added to aspirin, are beneficial following coronary intervention for the prevention of recurrent ischemic events as well as stent thrombosis. Clopidogrel has proven similar cardiac efficacy to ticlopidine, but with fewer gastrointestinal and hematologic side effects.6 A 300 mg loading dose of clopidogrel can achieve 85% platelet inhibition.7 Unfractionated heparin has traditionally been the primary antithrombin agent used in patients with ACS undergoing PCI. However, there are many limitations to unfractionated heparin. In addition to the need for frequent and continual monitoring of its anticoagulant effects, unfractionated heparin can also stimulate platelet aggregation and may induce thrombocytopenia. LMWHs overcome many of these limitations. Enoxaparin has been demonstrated to be superior to unfractionated heparin in patients with ACS (unstable angina, non-Q wave myocardial infarction, ST-elevation myocardial infarction).8–10 Limited data, however, are available for enoxaparin in the setting of PCI. Two open-label trials have examined the safety of intravenous enoxaparin in patients undergoing coronary intervention.11 These trials suggest that intravenous enoxaparin may be as efficacious as unfractionated heparin with less risk. The CRUISE study, a randomized clinical trial comparing enoxaparin and unfractionated heparin as an adjunct to eptifibatide in patients undergoing intracoronary stent procedures, has been reported at the 2001 American Heart Association meeting but is not yet published.12 This trial also reports similar efficacy and clinical outcomes among the two heparin groups. Because many patients with ACS are immediately referred to the cardiac catheterization laboratory with little to no antithrombotic therapy pre-treatment, this study sought to examine the feasibility and safety of administering a combination of these novel antiplatelet and antithrombin therapies immediately prior to PCI. METHODS From October 1999 to May 2000, patients who presented with ACS (including ST-segment elevation myocardial infarction) and who were referred for early ( 75 mg of clopidogrel, > 4 hours duration of unfractionated heparin infusion, > 1 dose of enoxaparin, or any glycoprotein IIb/IIIa platelet receptor inhibitor. All patients were also excluded for baseline platelet counts

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