Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis

Am J Cardiol. 2009 Jan 1;103(1):5-10. doi: 10.1016/j.amjcard.2008.08.048. Epub 2008 Nov 13.


Stent thrombosis remains a significant pitfall of percutaneous coronary intervention (PCI). A recent trial observed that an adjusted loading dose (LD) of clopidogrel according to platelet monitoring decreases the rate of major adverse cardiovascular events after PCI. We investigated if such a strategy of a tailored clopidogrel LD according to platelet reactivity monitoring could decrease the rate of stent thrombosis. This multicenter prospective randomized study included 429 patients with a low clopidogrel response after a 600-mg LD undergoing PCI. Patients were randomized to a control group (n = 214) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 215). In the VASP-guided group, patients received up to 3 additional 600-mg LDs of clopidogrel to obtain a VASP index <50% before PCI. The primary end point was the rate of stent thrombosis at 1 month. Secondary end points were rates of major adverse cardiovascular events and bleeding. Patients in the 2 groups had a high body mass index and were often diabetic (control vs VASP-guided group 28 +/- 5.1 vs 27.9 +/- 4.7 kg/m(2), p = 0.8, and 39% vs 33%, p = 0.2, respectively). PCI was performed in most patients for acute coronary syndrome in the 2 groups (52.3% vs 50.7%, p = 0.8). Despite a 2,400-mg LD of clopidogrel, 8% of patients in the VASP-guided group remained low responders. The rate of stent thrombosis was significantly lower in the VASP-guided group (0.5% vs 4.2%, p <0.01). The rate of major adverse cardiovascular events was also higher in the control group (8.9% vs 0.5%, p <0.001). There was no difference in the rate of bleeding (2.8% vs 3.7%, p = 0.8). In conclusion, a tailored clopidogrel LD according to platelet reactivity monitoring decreases the rate of early stent thrombosis after PCI without increasing bleeding.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Aged
  • Angina Pectoris / diagnosis
  • Angina Pectoris / surgery*
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Clopidogrel
  • Coronary Angiography
  • Coronary Thrombosis / blood
  • Coronary Thrombosis / diagnostic imaging
  • Coronary Thrombosis / prevention & control*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Graft Occlusion, Vascular / blood
  • Graft Occlusion, Vascular / diagnostic imaging
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Male
  • Monitoring, Physiologic
  • Myocardial Revascularization / methods*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine