Abstract 16530: Interaction Between 2C19*2 Gene Polymorphism, CYP3A4-Metabolyzed Statins and on-Treatment Platelet Reactivity: A Randomized Study Between Rosuvastatin and Atorvastatin.
Background: There is conflicting evidence suggesting that CYP3A4-metabolyzed statins may interfere with clopidogrel bioactivation. In previous studies, 2C19*2 genotype has been associated with decreased clopidogrel anti-platelet effect. We investigated whether carriers of the 2C19*2 allele are more susceptible to an adverse interaction between CYP3A4-metabolyzed statins and clopidogrel.
Methods: Following PCI, 107 patients not on proton pump inhibitors were randomized to atorvastatin 80mg qd (3A4-metabolyzed) or rosuvastatin 20mg qd. Maximal platelet aggregation (MPA) and platelet reactivity index (PRI) were measured after 30 days of uninterrupted clopidogrel and statin therapy. MPA was measured with light transmission aggregometry after stimulation with 5 μmol/L ADP. PRI was measured by vasodilator-stimulated phosphoprotein phosphorylation.
Results: Carriers of the 2C19*2 polymorphism were equally distributed across groups (atorvastatin 29.8%; rosuvastatin 33.3%;p=0.7). MPA was 48.2 +/−14.2% in carriers and 40.4+/−14.0% in non-carriers (p=0.009). No difference in MPA was found between atorvastatin and rosuvastatin patients (41.5 +/−13.7% vs 44.0 +/−15.2%; p=0.4). In 2C19*2 carriers, as well as in non-carriers, no difference in MPA was seen between patients treated with atorvastatin and those treated with rosuvastatin (figure 1). No interaction was found between 2C19*2 gene polymorphism, statin allocation and MPA (p=0.6).
Conclusion: In both carriers and non-carriers of the 2C19*2 gene polymorphism, the use of a 3A4-metabolyzed statin did not decrease the anti-platelet effect of clopidogrel. These findings suggest that 2C19*2 carriers may not be at a higher risk of CYP3A4 metabolism-based drug interactions with clopidogrel than non-carriers. Our observations, based on randomized data, do not do not suggest that the choice of a specific statin has an impact on platelet reactivity among patients treated with clopidogrel following PCI.
- © 2010 by American Heart Association, Inc.