Raising the loading dose of clopidogrel: aiming at the proper target?

András Komócsi

Heart Institute, Medical Faculty, University of Pécs, H-7624 Pécs, 13 Ifjúság u., Hungary, Tel: +36 72 536 001/5660, Fax: +36 72 536 387, E-mail address: andras.komocsi{at}aok.pte.hu

Tünde Pintér

Heart Institute, Medical Faculty, University of Pécs, H-7624 Pécs, 13 Ifjúság u., Hungary

Iván G. Horváth

Heart Institute, Medical Faculty, University of Pécs, H-7624 Pécs, 13 Ifjúság u., Hungary

With great interest, we read the excellent article of Angiolillo et al.1 which attempted to characterize the effect of 600 mg loading dose (LD) clopidogrel in patients undergoing coronary stenting (CS). Supplementation of aspirin with thienopyridines resulted in reduction of acute–subacute thrombotic complications of stent implantation. Despite the individual variability characterized with several laboratory tests, no study has yet proven that less effective dual antiplatelet therapy has causal relationship with the occurrence of acute stent thrombosis (AST).

A growing number of publications witness the enthusiasm of interventionalists to find better dosages of antiplatelet therapy. However, it is hard to reason the use of higher LD in all patients.

The current regimen reduced the AST frequency to 1–7%. This year we encountered 26 AST (1.7%). In six cases, occlusion occurred within the first hour after PCI, reflecting rather the ineffectiveness of the heparin administered during the intervention. In three patients, non-compliance was found. In 13 cases, stent thrombosis appeared >72 h after the intervention when effective clopidogrel therapy independently of the LD should have been achieved. Optical aggregometry of AST patients (to ADP, collagen, and adrenaline) showed no significant difference at median 12 days (IQR 5.5–51) after PCI when compared with 88 post-CS controls. This finding makes it implausible that resistance to the antiplatelets would play an important role in late ASTs. Using arbitrary criteria for responsiveness, Angiolillo et al. found 33.3–82.5% of patients to be responsive after 300 mg LD. This delineates a group of patients supposed to be at risk for AST 10 times higher than the real frequency of this complication. These data make the specificity of this approach questionable.

The causes underlying AST are not uniform. Patients stented in acute settings, in the presence of various degrees of distal embolization and impaired flow after CS, as cases with untreated marginal dissection or with scanty outflow tract are admittedly at higher risk. The group of Angiolillo has lately published data supporting that in overweight patients, the laboratory response to clopidogrel may be compromised and proposed different dosage for patients with higher body weights, despite the lacking proof for relationships of the body mass and AST frequency.2

On the basis of our institutional experience, we estimate that a higher LD would improve treatment only in a fraction of patients. The favourable side effect profile of clopidogrel in 75 mg daily doses was demonstrated. However, unnecessary rises of the LD would probably result in both needlessly elevated costs and higher frequency of adverse effects.

References

  1. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J 2004;25:1903–1910.[Abstract/Free Full Text]
  2. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Platelet aggregation according to body mass index in patients undergoing coronary stenting: should clopidogrel loading-dose be weight adjusted? J Invasive Cardiol 2004;16:169–174.[Medline]




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