Randomized, double‐blind comparison of effects of abiciximab bolus only vs. on‐label regimen on ex vivo inhibition of platelet aggregation in responders to clopidogrel undergoing coronary stenting

Abstract

Summary. Background: On top of aspirin, an abciximab bolusonly regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time. Objectives: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry. Patients/Methods: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600-mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as ‡ 50% 5 lmol L ; P = 0.01) and platelet count mean drop (41.7 ± 57 vs. 18.6 ± 34 10 9 L )1 ; P = 0.042) were significantly reduced in the bolus-only arm. Conclusions: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs.Keywords: abciximab, aggregometry, bolus, pharmacology, platelets.The studies establishing the optimal therapeutic regimen of abciximab for use in the catheterization laboratory antedated the adoption of coronary stents and the widespread use of thienopyridines [1,2]. In the EPIC study, an abciximab bolusonly strategy was compared with both placebo and the current on-label abciximab regimen of bolus followed by12-h infusion in patients undergoing balloon angioplasty and receiving concomitant treatment with aspirin and unfractionated heparin [2]. The cumulative rate of major adverse cardiac events was similarly reduced in the bolus-only arm (2.9%) and bolus + infusion arm (2.4%) as compared with placebo (5.3%) within the first 6 h after intervention [3]. However, higher rates of myocardial infarction and urgent target vessel revascularization were noted thereafter in the bolus arm as compared with bolus + infusion throughout 30 days [3].In the absence of concomitant P2Y 12 inhibition, withholding abciximab post-bolus infusion results in an approximately 30% drop in inhibition of platelet aggregation (IPA) at 6 h [1,4].

Out-of-hospital cardiac arrest: contemporary management and future perspectives

“…There is recent evidence that administration of eptifibatide in this setting results in profound platelet inhibition for at least 22 h 81. Similarly, it has been demonstrated in patients with STEMI and no cardiac arrest that a bolus of abciximab without additional infusion might be sufficient 82. Cangrelor, a novel intravenous P2Y12 inhibitor, is a promising agent in this setting due to its rapid onset (and offset) of action and its effectiveness in platelet inhibition,83 but data are lacking.…”

Abciximab in the management of acute myocardial infarction with ST-segment elevation: evidence-based treatment, current clinical use, and future perspectives

“…However, a recent study showed that withholding abciximab maintenance infusion does not impair platelet inhibition in patients receiving a 600 mg loading dose of clopidogrel 38. Similarly, Christ et al have shown that intracoronary abciximab bolus-only administration with oral P2Y 12 inhibitor (600 mg of clopidogrel or 60 mg of prasugrel) initiation effectively inhibited overall platelet reactivity for at least 48 hours, which brings the value of continuous abciximab infusion into question 39.…”

Contemporary use of glycoprotein IIb/IIIa inhibitors

“…In EPILOG, the successor to EPIC, heparin doses were reduced to the currently recommended bolus dose of 70 IU/kg (2). A recent study even showed that withholding abciximab maintenance infusion does not impair platelet inhibition in patients receiving a high loading dose of clopidogrel (21). Abciximab is eliminated through the reticuloendothelial system, including the spleen, and does not require dose adjustment in the setting of renal insufficiency (ǠTable 1) (22).…”