Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation.

Inhibit Platelet Aggregation To the Editor: Lau et al1 recently reported that coadministration of CYP3A4metabolized statins (atorvastatin, simvastatin, and lovastatin) but not pravastatin (fluvastatin and rosuvastatin) inhibited the “antiplatelet activity of clopidogrel in a dose-dependent manner,” using an in vitro point-of-care MICROS cell counter (ABX Diagnostics) and the Plateletworks test platform (Helena Laboratories). Platelet activity is measured by the combination of the following three tests: (a) platelet aggregation by adenosine diphosphate (ADP) or collagen-induced whole blood (or platelet-rich plasma) platelet aggregometry, (b) platelet adhesion by ex-vivo perfusion (Badimon) chamber,2 and (c) platelet activation by flow-cytometry measurement of the surface membrane expression of CD62p (p-selectin, GMP140) in the whole blood.3–5 All three tests are needed to test platelet function. Clopidogrel, an ADP receptor antagonist, selectively and irreversibly inhibits ADP-induced platelet activation and aggregation, thereby preventing atherothrombosis. In their interesting and provocative article, Lau et al1 found that atorvastatin, and not pravastatin, blunted the in vitro antiaggregation effect of clopidogrel in patients after stent deployment. However, the authors measured only the platelet antiaggregation pathway and left the other two pathways (platelet adhesion and platelet activation) unexplored. Blocking only one pathway does not necessarily predict stent restenosis (and/or in-stent thrombosis) and/or a worse clinical outcome. I suggest, therefore, that the authors assess the impact of clopidogrel alone and its administration with atorvastatin or pravastatin on platelet adhesion and activation before concluding that CYP3A4-metabolized statins, and not pravastatin, inhibit the “antiplatelet activity of clopidogrel.”