Atorvastatin Does Not Affect the Antiplatelet Potency of Clopidogrel When It Is Administered Concomitantly for 5 Weeks in Patients With Acute Coronary Syndromes

Abstract

Background-The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins.We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes (ACS) could affect the antiplatelet potency of clopidogrel. Methods and Results-Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study. Patients were randomized to receive daily either 10 mg of atorvastatin (nϭ21) or 40 mg of pravastatin (nϭ24). Thirty patients who underwent percutaneous coronary intervention (PCI) received a loading dose of 375 mg of clopidogrel, followed by 75 mg/d for at least 3 months. In the remaining 15 patients who refused to undergo PCI, clopidogrel therapy was not administered. Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel. The serum levels of soluble CD40L and the adenosine 5Ј-diphosphate-or thrombin receptor activating peptide-14 -induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 minutes after admission) and 5 weeks later. Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation, nor did clopidogrel influence the therapeutic efficacy of atorvastatin. Conclusions-Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients.

Aspirin and Clopidogrel

“…87 Interference with clopidogrel metabolism by other drugs that are frequently given to patients with atherosclerosis, such as atorvastatin, 86,88 can increase the number of patients who are resistant to clopidogrel, although this is still a controversial issue. 89,90 Clinical Consequences A recent study of 60 patients undergoing coronary angioplasty confirmed the high interindividual variability of platelet inhibition by clopidogrel and showed that patients with clopidogrel resistance (mean ADP-induced platelet aggregation on day 6 of treatmentϭ103Ϯ8% of baseline) are at increased risk for recurrent cardiovascular events. 91 …”

Clinical importance of aspirin and clopidogrel resistance

“…Lau et al [63] showed that atorvastatin promoted clopidogrel resistance at 10 mg, 20 mg and 40 mg (P = 0.027, P = 0.002 and P = 0.001, respectively). On the other hand, Mitsios et al [64] reported that daily doses of 10 mg of atorvastatin did not result in a decreased clopidogrel response over a 5-wk period. In the same study, clopidogrel significantly attenuated platelet aggregation in 3 different concentrations of ADP in the presence of no statin, atorvastatin, or pravastatin (P < 0.01, P < 0.01, and P < 0.02 at 2 μmol, 5 μmol, and 10 μmol of ADP, respectively).…”

Update on Statins: 2003

“…14 Although a potential drug interaction be-tween clopidogrel and atorvastatin was suspected on the basis of the inhibition of clopidogrel activation by atorvastatin via its effects on CYP3A4, 15,16 more recent data question the clinical significance of this interaction. 17,18 Atorvastatin and fluvastatin have minimal renal excretion, and dose adjustment of these statins in patients with renal insufficiency is therefore unnecessary. 19 Although it was initially suspected that gemfibrozil increased statin levels by inhibiting CYP450 enzymes, it is now thought that its inhibition of glucuronidation of statins may be a likely culprit.…”