Antiplatelet effects of clopidogrel dose adjustment (75 mg/d vs 150 mg/d) after carotid stenting

J Vasc Surg. 2014 Aug;60(2):428-35. doi: 10.1016/j.jvs.2014.01.068. Epub 2014 Mar 11.

Abstract

Objective: Clopidogrel plays a central role in the treatment of patients undergoing carotid artery stenting (CAS). The objective was to evaluate the effect of clopidogrel (75 mg/d) on platelet reactivity in responders and nonresponders and the antiplatelet effect of different doses of clopidogrel in patients with high on-treatment reactivity (OTR) after CAS.

Methods: Patients with high OTR (defined by VerifyNow (Accumetrics, San Diego, Calif) assay as ≥230 P2Y12 reaction units [PRU]) were randomly assigned in a 1:1 ratio to group 1 (standard-dose clopidogrel therapy: 75 mg/d for 30 days) or group 2 (high-dose clopidogrel: 150 mg/d for 30 days).

Results: The study enrolled 214 patients. Of these, 115 (53.7%) were clopidogrel responders (group 0), and 99 (46.3%) had high OTR (clopidogrel nonresponders); of which, 50 were randomly assigned to group 1 and 49 to group 2. At baseline, the PRU value did not differ between group 1 (288.50 ± 46) and group 2 (295.45 ± 47.2; P = .308). Patients displayed reduced mean platelet reactivity levels at 30 days in group 1 (238.96 ± 72.25; P < .001) and group 2 (201.85 ± 77.8; P < .001). Although high-dose clopidogrel resulted in more intense platelet function inhibition, the differences between median 30-day PRU values (P = .483) and the percentage change of PRU (P = .442) for groups 1 and 2 were not significant. The incidences of transient ischemic attack, stroke, or death at up to 30 days after CAS in the high-OTR patients were similar between groups 1 and 2 (P = .481).

Conclusions: Patients with high OTR undergoing CAS treated with standard-dose and double-dose clopidogrel had significantly reduced platelet reactivity after 30 days. The double dose did not result in statistically significantly greater reductions in reactivity compared with the standard dose.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty / adverse effects
  • Angioplasty / instrumentation*
  • Angioplasty / mortality
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / diagnosis
  • Carotid Artery Diseases / mortality
  • Carotid Artery Diseases / therapy*
  • Clopidogrel
  • Female
  • Humans
  • Ischemic Attack, Transient / etiology
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Function Tests
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Receptors, Purinergic P2Y12 / drug effects*
  • Receptors, Purinergic P2Y12 / metabolism
  • Spain
  • Stents*
  • Stroke / etiology
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Ticlopidine