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.

Resistance to clopidogrel: A review of the evidence

“…Since then, other investigators have refuted the relevancy of this interaction (52)(53)(54)(55)(56)(57)(58). Retrospective analyses of data from the Plavix Reduction of New Thrombus Occurrence (PRONTO) trial, the Clopidogrel for the Reduction of Events During Observation (CREDO), and the Maximal Individual Therapy of Acute Myocardial Infarction PLUS (MITRA PLUS) registry did not find that concomitant use of statins compromised the antiplatelet effect of clopidogrel assessed both by platelet function and clinical end points (52)(53)(54).…”

“…Four prospective studies, of which three were randomized, also evaluated the possible interaction between statins and clopidogrel (55)(56)(57)(58). Two studies found that CYP3A4- a.…”

Clopidogrel Resistance

“…Four of the studies 48,49,50,51 suggest that concomitant treatment with clopidogrel and CYP 3A4 metabolised statins attenuates the antiplatelet effect of clopidogrel, whereas the remaining three studies 52,53,54 show that co-administration is without influence of the antiplatelet effect of clopidogrel. All of these studies are hampered by a variable amount of deficiencies in design, and comparisons of results are haphazardous due to these substantial differences in methods and study design.…”

CD40/CD40L system and vascular disease

“…In addition to their role in modulating CD40L in the setting of asymptomatic hypercholesterolaemia [81,87], statins have proven effective in patients with stable CAD [88] and ACS [89,90]. In patients with ACS enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study [91], atorvastatin started within 24-96 h of admission abrogated the risk of recurrent cardiovascular events associated with high sCD40L over 16 weeks of treatment.…”