Clopidogrel provides significantly greater inhibition of platelet activity than aspirin when combined with atorvastatin after coronary artery bypass grafting: a prospective randomized study

Clin Appl Thromb Hemost. 2010 Apr;16(2):189-98. doi: 10.1177/1076029609344980. Epub 2009 Aug 23.

Abstract

Objective: We aimed to compare the effects of 2 different antiplatelet agents on platelet activity in patients receiv- ing atorvastatin after coronary artery bypass grafting (CABG).

Methods: We prospectively randomized 50 patients undergoing CABG into 2 groups; group 1 started to receive atorvastatin (10 mg) plus clopidogrel (75 mg; C + A, n = 25) and group 2 atorvastatin (10 mg) and acetylsalicylic acid (ASA; 300 mg, ASA + A, n = 25) daily on postoperative day 1 and continued for 6 months after operation. Adenosine diphosphate (ADP)-induced platelet aggregation and the expressions of glycoprotein (Gp) IIb, GpIIIa, P-selectin, and fibrinogen (Fg) and low-density lipoprotein (LDL) binding to platelets were assessed preoperatively and at postoperative days 7, 90, and 180.

Results: The mean age of the patients was 59.6 +/- 7.6 years, and 82% of the patients were males. The combination of C + A markedly inhibited ADP-induced platelet aggregation compared with ASA + A at postoperative days 90 and 180 (52% +/- 6.0% vs 56% +/- 7.25% and 19.6% +/- 3.2% vs 37% +/- 4.1%, P = .039 and P = .0001, respectively). The therapy of C + A significantly suppressed the expressions of GpIIIa at postoperative days 7, 90, and 180 (P = .0001, P = .0001, and P = .0001, respectively) and P-selectin at postoperative days 90 and 180 (P = .035 and P = .002, respectively) when compared to ASA + A. The expression of GpIIb was also significantly depressed at postoperative day 180 in group 1 when compared to group 2 (P = .0001). Low-density lipoprotein binding was significantly increased at day 180 postoperatively in both the groups (basal: 42.9% +/- 5.6% vs 45.3% +/- 4.4% and day 180: 60.3% +/- 4.6% vs 61.8% +/- 5.7%, P = .0001).

Conclusions: Our results demonstrate that the combination of C + A is more effective than that of ASA + A in inhibiting ADP-mediated platelet aggregation and expression of major platelet receptors after CABG.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Aged
  • Aspirin / administration & dosage
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Atorvastatin
  • Clopidogrel
  • Comorbidity
  • Coronary Artery Bypass*
  • Coronary Disease / blood
  • Coronary Disease / complications
  • Coronary Disease / surgery
  • Drug Therapy, Combination
  • Female
  • Fibrinogen / analysis
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • P-Selectin / analysis
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / analysis
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Pyrroles
  • Adenosine Diphosphate
  • Fibrinogen
  • Atorvastatin
  • Clopidogrel
  • Ticlopidine
  • Aspirin