The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Atorvastatin Reduces the Ability of Clopidogrel to Inhibit Platelet Aggregation: A New Drug–Drug Interaction
Open accessAbstract
Background— We observed that the prodrug clopidogrel was less effective in inhibiting platelet aggregation with coadministration of atorvastatin during point-of-care platelet function testing. Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4. Methods and Results— Platelet aggregation was measured in 44 patients undergoing coronary artery stent implantation treated with clopidogrel or clopidogrel plus pravastatin or atorvastatin, and in 27 volunteers treated with clopidogrel and either erythromycin or troleandomycin, CYP3A4 inhibitors, or rifampin, a CYP3A4 inducer. Atorvastatin, but not pravastatin, attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner. Percent platelet aggregation was 34±23, 58±15 ( P =0.027), 74±10 ( P =0.002), and 89±7 ( P =0.001) in the presence of clopidogrel and 0, 10, 20, and 40 mg of atorvastatin, respectively. Erythromycin attenuated platelet aggregation inhibition (55±12 versus 42±12% platelet aggregation; P =0.002), as did troleandomycin (78±18 versus 45±18% platelet aggregation; P <0.0003), whereas rifampin enhanced platelet aggregation inhibition (33±18 versus 56±20% platelet aggregation, P =0.001). Conclusions— CYP3A4 activates clopidogrel. Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation. Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel.
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IN VITRO AND IN VIVO DRUG INTERACTIONS INVOLVING HUMAN CYP3A
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Cited by
Patrono, C., Coller, B., Dalen, J. E., Fitz Gerald, G. A., Fuster, V., Gent, M., Hirsh, J., & Roth, G. (2001) · Chest · doi:10.1378/chest.119.1_suppl.39s · Cited by 963
Safety of Statins: Focus on Clinical Pharmacokinetics and Drug Interactions
Bellosta, S., Paoletti, R., & Corsini, A. (2004) · Circulation · doi:10.1161/01.cir.0000131519.15067.1f · Cited by 578
Kennedy, J., Hill, M. D., Ryckborst, K. J., Eliasziw, M., Demchuk, A. M., & Buchan, A. M. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70250-8 · Cited by 551
Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel
Siller-Matula, J. M., Lang, I., Christ, G., & Jilma, B. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.07.055 · Cited by 262
Drug Therapy in the Heart Transplant Recipient: Part IV: Drug–Drug Interactions
Page, R. L., Miller, G. G., & Lindenfeld, J. (2005) · Circulation · doi:10.1161/01.cir.0000151805.86933.35 · Cited by 100
Metadata
- Authors
- Lau, W. C., Waskell, L. A., Watkins, P. B., Neer, C. J., Horowitz, K., Hopp, A. S., Tait, A. R., Carville, D. G. M., Guyer, K. E., & Bates, E. R.
- Venue
- Circulation
- Published
- 2003-01-07
- Volume
- 107
- Issue
- 1
- Pages
- 32-37
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1974238774
- Cited by
- 688
- References
- 32
- FWCI
- 45.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lau, W. C., Waskell, L. A., Watkins, P. B., Neer, C. J., Horowitz, K., Hopp, A. S., Tait, A. R., Carville, D. G. M., Guyer, K. E., & Bates, E. R. (2003). Atorvastatin Reduces the Ability of Clopidogrel to Inhibit Platelet Aggregation: A New Drug–Drug Interaction. Circulation. https://doi.org/10.1161/01.cir.0000047060.60595.cc
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
