Inpharma 1632 - 5 Apr 2008

Individualised clopidogrel LDsimprove PCI outcomes

Giving a clopidogrel loading dose (LD) beforepercutaneous coronary intervention (PCI) to reduce therisk of major cardiac adverse events (MACEs) is standardpractice in cardiac catheterisation laboratories.However, the reduction in platelet activity achieved withthis drug varies widely from person to person.

To address this issue, researchers from France usedthe vasodilator-stimulated phosphoprotein (VASP) indexto assess patients’ responses to clopidogrel. This simpleblood test has a 100% negative predictive value forpredicting MACE after PCI, using a cut-off value of 50%of platelet response; consequently, a low response toclopidogrel was defined as post-treatment plateletreactivity of ≥ 50%.

The researchers evaluated data from 162 patients witha low response undergoing routine PCI for acutecoronary syndrome or stable angina and presented theirfindings at a late-breaking session of the 57th AnnualScientific Session of the American College of Cardiology.Participants were randomised to receive pretreatmentwith aspirin 250mg plus clopidogrel 600mg (n = 84) orwith VASP-guided clopidogrel LDs, which involved theadministration of up to three additional LDs every24 hours until VASP was < 50% (maximum 2400mg).

Overall, VASP-guided LDs achieved an adequateresponse in 86% of recipients. After 30 days of follow-up, none of those patients who received VASP-guidedLDs had a MACE (myocardial infarction, repeat PCI,bypass surgery or death) [see table]. In contrast, 10% ofthe standard care group has incurred such an event.

Outcomes at 30 daysClopidogrel LD

Single dose VASP-guided

MACE, n (%):Cardiovascular death 2 (2) 0Acute and subacute 4 (5)* 0stent thrombosis

Revascularisation 2 (2) 0Overall MACE 8 (10)** 0

* p = 0.059; ** p = 0.007

Moreover, there were no significant difference in therates of bleeding between the single LD and VASP-guided LD group (5% vs 4%, respectively); there wasone episode of major bleeding in each group.

Lead investigator on the trial, Dr Laurent Bonello,from Hopital Universitaire Nord, Marseille, France,concluded that "tailoring the loading dose of clopidogrelusing platelet monitoring seems to be the best way todecrease the rate of major adverse cardiac events, inparticular, stent thrombosis".

A discussant of the study suggested that the results ofthis study indicate a move away from a ‘one size fits all’approach to dosing of P2Y12 receptor antagonists, andthat VASP-guided therapy "seems optimal to preventMACE in patients".Bonello L, et al. Platelet monitoring of clopidogrel response using VASPphosphorylation index decrease rate of major adverse cardiovascular events inpatients with clopidogrel resistance: a multicentre randomized prospective study.57th Annual Scientific Session of the American College of Cardiology: LateBreakers : (plus oral presentation) abstr. 2401-9, 29 Mar 2008 801034914

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Inpharma 5 Apr 2008 No. 16321173-8324/10/1632-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved