There are conflicting data regarding whether statins predominantly metabolized by CYP3A4 reduce the metabolism of Clopidogrel ( Plavix ) to its active metabolite and diminish its clinical efficacy.

CHARISMA investigators evaluated the potential impact of Clopidogrel and statin interaction in a randomized, placebo-controlled trial with long-term follow-up.

The CHARISMA trial was a randomized trial comparing long-term 75 mg/day Clopidogrel versus placebo in patients with cardiovascular disease or multiple risk factors on Acetylsalicylic acid ( Aspirin ).
The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death at median follow-up of 28 months.

Researchers performed a secondary analysis evaluating the interaction of Clopidogrel versus placebo with statin administration, categorizing baseline statin use to those predominantly CYP3A4 metabolized ( Atorvastatin [ Lipitor ], Lovastatin [ Mevacor ], Simvastatin [ Zocor ]; CYP3A4-MET ) or others ( Pravastatin [ Pravachol ], Fluvastatin[ Lescol ]; non-CYP3A4-MET ).

Of 15,603 patients enrolled, 10,078 received a statin at baseline ( 8,245 CYP3A4-MET, 1,748 non-CYP3A4-MET ) and 5,496 did not.

For the overall population, the primary end point was 6.8% with Clopidogrel and 7.3% with placebo ( hazard ratio [ HR ] 0.93; p = 0.22 ).
This was similar among patients on CYP3A4-MET ( 5.9% Clopidogrel, 6.6% placebo, HR 0.89; p = 0.18 ) or non-CYP3A4-MET statin ( 5.7% Clopidogrel, 7.2% placebo, HR 0.78; p = 0.19 ).
There was no interaction between statin types and randomized treatment ( p = 0.69 ).

Patients on Atorvastatin ( n = 4,127 ) ( 5.7% Clopidogrel, 7.1% placebo, HR 0.80; p = 0.06 ) or Pravastatin ( n = 1,440 ) ( 5.1% Clopidogrel, 7.0% placebo, HR 0.72; p = 0.13 ) had similar event rates.

According to Authors, despite theoretic concerns and ex vivo testing suggesting a potential negative interaction with concomitant Clopidogrel and CYP3A4-MET statin administration, there was no evidence of an interaction clinically in a large placebo-controlled trial with long-term follow-up.

Source: Journal of American College of Cardiology, 2007

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