Safety and Efficacy of Combined Use of Low Molecular Weight Heparin (Enoxaparin, Lovenox) and Glycoprotein IIb/IIIa Receptor Antagonist (Eptifibatide, Integrelin) During Nonemergent Coronary and Peripheral Vascular Intervention

Abstract

Coronary and peripheral intervention requires intraprocedural anticoagulation to prevent intraluminal thrombosis. Traditionally, unfractionated heparin (UFH) is administered during the procedure to achieve activated clotting time (ACT) of 300 to 400 seconds. When the intravenous IIb/IIIa antagonists are also used, the recommended ACT is 250 to 300 seconds because higher anticoagulation (ACT, 300-400 seconds) is accompanied by an unacceptable bleeding complication rate without added benefits. Because low molecular weight heparin has a more predictable anticoagulant effect and a higher anti-factor Xa/anti-factor IIa ratio, allows better bioavailability, is resistant to inhibition by activated platelets, and does not require routine monitoring using ACT, its use for intraprocedural anticoagulation (instead of UFH) has been an area of increasing interest. The safety and efficacy of coadministration of low molecular weight heparin with IIb/IIIa antagonists have not been adequately evaluated. We report a study of prospective evaluation of the safety and efficacy of combined use of intravenous enoxaparin and intravenous eptifibatide during nonemergent coronary and peripheral vascular intervention in 93 consecutive procedures performed on 56 patients. The procedural success rate was 99% (92/93 procedures), the acute clinical success rate was 98% (54/55 patients), the major bleeding complication rate was 2% (1/56 patients), and the vascular complication rate was 0.0%. In conclusion, the use of intravenous enoxaparin in conjunction with intravenous eptifibatide during nonemergent coronary and peripheral vascular intervention is safe and effective and eliminates the need for routine measurement of ACT during the procedure.

Glycoprotein IIb-IIIa receptor inhibition with eptifibatide in percutaneous intervention for symptomatic peripheral vascular disease: The circulate pilot trial

“…The high degree of platelet activation and the increased role of agonists other than TxA 2 , ADP, or thrombin in PAD [11] suggest that, when added to the background of conventional antithrombotic therapy (aspirin, a thienopyridine, and an antithrombin agent), GP IIb‐IIIa inhibitors may reduce ischemic complications associated with PAD. This concept is supported by the results of the present trial and recent studies of GP IIb‐IIIa inhibitors in PAD [5, 12, 13]. In a study by Khosla et al, the use of eptifibatide in combination with the low‐molecular‐weight heparin enoxaparin (Lovenox®, Aventis, Inc., Bridgewater, New Jersey) was safe and effective in patients undergoing non‐emergent coronary or peripheral vascular interventions [5].…”

“…Despite the strong pathophysiologic rationale, clinical experience with GP IIb‐IIIa inhibitors in peripheral interventions is limited [5, 6]. To evaluate the safety and feasibility of GP IIb‐IIIa inhibition in peripheral interventions, we conducted a pilot trial with eptifibatide (INTEGRILIN®, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, and Schering‐Plough Corporation, Kenilworth, New Jersey) in patients undergoing PTA or stenting for severe claudication or critical limb ischemia.…”

Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin

“…Both tirofiban and eptifibatide in combination with enoxaparin have been shown to reduce parameters of ischemia as compared with their combination with UFH (16,17). The combination of GP IIb/IIIa inhibitors with enoxaparin has also been shown to be safe (12)(13)(14)(15)(16)(17). Given the results of the recent clinical efficacy trials and our findings regarding antithrombotic activity, the combination of eptifibatide with enoxaparin appears to exert a more potent antithrombotic effect than eptifibatide and UFH in the doses tested.…”

“…Recently, the concept of combining LMWH with GP IIb/IIIa inhibitor therapy has gained support (12)(13)(14)(15)(16)(17). The safety of this combination therapy has been demonstrated when using abciximab or eptifibatide and intravenous enoxaparin during PCI (12)(13)(14) and the combination of tirofiban or eptifibatide given with subcutaneous enoxaparin to ACS patients (15)(16)(17).…”

“…The safety of this combination therapy has been demonstrated when using abciximab or eptifibatide and intravenous enoxaparin during PCI (12)(13)(14) and the combination of tirofiban or eptifibatide given with subcutaneous enoxaparin to ACS patients (15)(16)(17). Recent data also suggest that the combination of a GP IIb/IIIa inhibitor with enoxaparin has better clinical efficacy than the combination with UFH.…”