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Effects of Administration of Glycoprotein IIb/IIIa Receptor Antagonists in Patients with Failed Thrombolysis

A Pilot Study

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Abstract

Aim

To evaluate the effectiveness of glycoprotein (GP) IIb/IIIa receptor antagonists in patients with acute myocardial infarction (AMI) who have undergone unsuccessful thrombolysis.

Design

Randomised, prospective, single-blind trial.

Patients and Participants

84 patients (62 males, 22 females, aged 40 to 80 years) in whom thrombolysis had failed out of a total of 225 consecutive patients admitted to hospital with suspected AMI.

Methods

In suitable patients, thrombolysis with ‘accelerated’ recombinant tissue-type plasminogen activator (rtPA) was initiated. Patients in whom thrombolysis was unsuccessful were randomised within 4 hours of onset of symptoms into two groups. Unsuccessful thrombolysis was defined as failure to show any sign of reperfusion after administration of the first 65mg of rtPA, or as recurrence of pain and ST-segment elevation within 30 to 60 minutes of the end of full thrombolysis (100mg of rtPA). The 42 patients in group 1 (GPIIb/IIIa) stopped thrombolysis (if still being administered) and received treatment with an intravenous bolus plus infusion of GPIIb/IIIa antagonists (abciximab or tirofiban or eptifibatide) plus heparin according to the Thrombolysis in Myocardial Infarction (TIMI)-14 schedule and aspirin. The 42 patients in group 2 (placebo) received the full dose of rtPA, even if there was no sign of reperfusion, and placebo together with standard heparin and aspirin. Patients without signs of reperfusion were immediately referred for rescue revascularisation.

Results

In group 1 (GPIIb/IIIa), 22 patients received rtPA 65mg and 20 patients received rtPA 100mg. 39 patients showed rapid reperfusion (4 ± 3 min) on treatment with GPIIb/IIIa antagonists, and only one required rescue percutaneous transluminal coronary angioplasty (PTCA). Coronarography after 12 to 72 hours demonstrated patency of the infarct-related artery in the 39 patients who showed rapid reperfusion. In group 2 (placebo), no patients showed reperfusion and all received rescue PTCA. Three patients in the GPIIb/IIIa group and two in the placebo group experienced bleeding-related adverse effects. Patients receiving GPIIb/IIIa antagonists showed a nonsignificantly reduced requirement for stent treatment and a reduction of angina at 30 days after treatment compared with the placebo group.

Conclusion

These preliminary data suggest the possibility of using GPIIb/IIIa receptor antagonists in patients with failed thrombolysis after AMI, with an acceptable increase in bleeding risk. We consider the demonstration of the safety of this combination as the most important result of this study.

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Correspondence to Pietro Di Pasquale.

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Di Pasquale, P., Sarullo, F.M., Cannizzaro, S. et al. Effects of Administration of Glycoprotein IIb/IIIa Receptor Antagonists in Patients with Failed Thrombolysis. Clin. Drug Investig. 21, 545–553 (2001). https://doi.org/10.2165/00044011-200121080-00003

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