Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14

Abstract

Aims Abciximab has previously been shown to enhance thrombolysis and improve myocardial perfusion when combined with reduced doses of alteplase. The purpose of the reteplase phase of TIMI 14 was to evaluate the effects of abciximab when used in combination with a reduced dose of reteplase for ST-elevation myocardial infarction. Methods and Results Patients (n=299) with ST-elevation myocardial infarction were treated with aspirin and randomized to a control arm with standard dose reteplase (10+10 U given 30 min apart) or abciximab (bolus of 0.25 mg. kg(-1)and 12-h infusion of 0.125 microg. kg(-1). min(-1)) in combination with reduced doses of reteplase (5+5 U or 10+5 U). Control patients received standard weight-adjusted heparin (bolus of 70 U. kg(-1); infusion of 15 U. kg(-1). h(-1)), while each of the combination arms with abciximab and reduced dose reteplase received either low dose heparin (bolus of 60 U. kg(-1); infusion of 7 U. kg(-1). h(-1)) or very low dose heparin (bolus of 30 U. kg(-1); infusion of 4 U. kg(-1). h(-1)). The rate of TIMI 3 flow at 90 min was 70% for patients treated with 10+10 U of reteplase alone (n=87), 73% for those treated with 5+5 U of reteplase with abciximab (n=88), and 77% for those treated with 10+5 U of reteplase with abciximab (n=75). Complete (>/=70%) ST resolution at 90 min was seen in 56% of patients receiving a reduced dose of reteplase in combination with abciximab compared with 48% of patients receiving reteplase alone. Conclusions Reduced doses of reteplase when administered in combination with abciximab were associated with higher TIMI 3 flow rates than reported previously for reduced doses of reteplase without abciximab and were at least as high as for full dose reteplase alone

Serum Levels of the Interleukin-1 Receptor Family Member ST2 Predict Mortality and Clinical Outcome in Acute Myocardial Infarction

“…Specifically, this study was an angiographic trial that evaluated several combinations of fibrinolytic with the glycoprotein IIb/IIIa antagonist abciximab. 8,9 The ENTIRE-TIMI 23 trial was an open-label, dose-ranging, multicenter study conducted between February 2000 and September 2001 to evaluate enoxaparin as adjunctive antithrombin therapy with various forms of pharmacological reperfusion, including full-dose tenecteplase and half-dose tenecteplase plus abciximab. 10 In both studies, patients were eligible for inclusion if they had a qualifying episode of ischemic discomfort of at least 30 minutes within 6 hours (ENTIRE) or 12 hours (TIMI 14) and exhibited at least 0.1-mV ST-segment elevation in 2 contiguous ECG leads.…”

Adjuvant Treatment With a Glycoprotein IIb/IIIa Receptor Inhibitor Increases the Therapeutic Window for Low-Dose Tissue Plasminogen Activator Administration in a Rat Model of Embolic Stroke

“…[3][4][5][6] Moreover, combination therapy in humans with myocardial infarction has been shown to result in improved cardiac microcirculatory function, as judged by ST-segment resolution. 7 Our previous animal studies of stroke demonstrating platelet aggregation formation in the ischemic microcirculation distal to an embolus of the middle cerebral artery (MCA) within 4 hours after initiation of the occlusion reinforce the theoretical benefit of antiplatelet therapy in protecting the microcirculation from damage that may prevent effective reperfusion even if the obstructing thrombus is lysed. 8 …”

Considerations in combination therapy: Fibrinolytics plus glycoprotein IIb/IIIa receptor inhibitors in acute myocardial infarction

“…14 Rates of TIMI grade 3 flow at 90 min were 70% in the reteplase control group, 73% in the abciximab plus half-dose reteplase (5 U + 5 U) group, and 77% in the abciximab plus reteplase (10 U + 5 U) group. There were no differences in flow rates observed according to low-dose or very-low-dose heparin use.…”

“…14 In the first arm, patients were randomized to standard-dose alteplase or standard-dose abciximab bolus plus infusion alone or in combination with a range of doses of alteplase or streptokinase; the control patients received standard weightadjusted heparin, whereas those receiving abciximab received low-dose heparin (60 U/kg bolus [maximum 4000 U] and 7 U/kg/h infusion [maximum 800 U/h]). 13 The most promising combination was the alteplase 50 mg (15 mg bolus; 35 mg infusion/60 min) plus abciximab (bolus 0.25 mg/kg; 12-h infusion: 0.125 µg/kg/min), along with low-dose or very-low-dose heparin (30 U/kg bolus; 4 U/kg/h infusion).…”