Same Dose of Drug, Different Magnitude of Effect?

   Glycoprotein IIb/IIIa receptor inhibitors have been demonstrated to reduce major adverse cardiac events (MACE) in patients undergoing coronary interventions, particularly when there is associated thrombus.^1,2 In this issue, Dr. Hansen and colleagues perform a meta-analysis³ of published studies in an effort to determine if the route of administration of abciximab (intravenous bolus versus intracoronary bolus of the same dose of drug) affects outcomes in patients undergoing percutaneous coronary intervention (PCI).    Abciximab is a murine-derived antibody fragment antigen binding (Fab) fragment that inhibits platelet aggregation by specifically binding the platelet’s IIb/IIIa surface receptor, which is the final common pathway for platelet aggregation. Abciximab’s platelet inhibition effect occurs in a dose-related manner. Local administration of the drug has been shown to increase pharmacological drug concentration gradients locally at the site of administration.^4–13 Ab- ciximab prevents fibrinogen, Von Willebrand factor, vitronectin and other adhesive molecules from binding the receptor, resulting in inhibition of platelet aggregation.    In most of the cases reviewed in this study, the intracoronary administration of drug was by simple bolus at the time of PCI, although there was one study in which it was administered by a dual- lumen catheter¹⁴ and one study where it was delivered beyond the area of occlusion.¹⁵ This study suggests that intracoronary administration of abciximab resulted in decreased mortality and a trend toward a reduction in overall MACE, even though it tended to be utilized more frequently in higher-risk patients. There were no re- ported adverse events suggestive of local toxicity associated with the intracoronary dosing route. Potential mechanisms of beneficial outcomes include more effective inhibition of local platelet function, thrombus dissolution and a local anti-inflammatory effect.^4,16    This provocative article suggests that the same dose of the same GP IIb/IIIa inhibitor may have dramatically different effects when administered via the intracoronary route rather than intravenously. Certainly, more study is needed. A randomized trial would be helpful in determining the true significance of these findings. The design of that study must evaluate the method of intracoronary infusion as well. A simple bolus via a guiding catheter could po- tentially be shunted away from the area obstructed by coronary thrombus. An infusion via a catheter that requires crossing an obstruction may risk embolization of thrombotic debris and may cause a temporal delay in drug administration. The elapsed time from the onset of symptoms until intracoronary drug administration may be crucial. The dwell time of the drug at the site of thrombus may be important. There are a multitude of variables in any pharmacological study that must be considered in assessing risks, benefits and cost effectiveness.

_________________________________________________ From the Cardiovascular Institute of the South, Houma, Louisiana. The author reports no conflicts of interest regarding the content herein. Address for correspondence: Craig Walker, MD, Vascular Laboratory, Cardiovascular Institute of the South, 225 Dunn Street, Houma, LA 70360. Email: craig.walker@cardio.com

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