Clopidogrel provides significantly greater inhibition of platelet activity than aspirin when combined with atorvastatin after coronary artery bypass grafting: a prospective randomized study.
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.
Tetik
Sermin
S
Department of Biochemistry, Faculty of Pharmacy, Marmara University, Istanbul, Turkey. stetik@marmara.edu.tr
Ak
Koray
K
Isbir
Selim
S
Eksioglu-Demiralp
Emel
E
Arsan
Sinan
S
Iqbal
Omer
O
Yardimci
Turay
T
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D000077144:Clopidogrel; D015897:Comorbidity; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000601:surgery; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D011183:Postoperative Complications / Q000517:prevention & control*; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011758:Pyrroles; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin