Interaction between statins and clopidogrel: is there anything clinically relevant?

Abstract

Since their introduction several years ago, the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors-the statins-have been widely used for hyperlipidemia and for the primary/secondary prevention of cardiovascular diseases. They have been shown to be safe as well as efficacious in a number of different clinical trials; however, studies have suggested that they can interact with other co-administered therapies. More recently, the thienopyridines have been successfully integrated with the conventional medical treatment of coronary disease as they showed effectiveness in reducing platelet activity both in stable and unstable settings. They also improve the outcome of patients treated with percutaneous coronary intervention. The potential interaction of statins and thienopyridines is a matter of concern. Despite some preclinical data suggesting an interaction between statins metabolized by the liver cytochrome P3A4-such as atorvastatin, lovastatin and simvastatin-and clopidogrel, there is no compelling clinical evidence to stop their co-administration.

Clopidogrel Has No Clinically Meaningful Effect on the Pharmacokinetics of the Organic Anion Transporting Polypeptide 1B1 and Cytochrome P450 3A4 Substrate Simvastatin

“…Simvastatin is a well tolerated drug, but its concentration-dependent muscle toxicity is a potentially serious adverse effect that has to be taken into consideration (Armitage 2007). The effect of simvastatin on the activation of clopidogrel has been studied widely due to concerns about the possibly reduced antiplatelet activity of clopidogrel in statin users (Vinholt et al, 2005;Bhindi et al, 2008;Siepmann et al, 2014). However, to our knowledge, the effect of clopidogrel on the pharmacokinetics of simvastatin has not been characterized previously.…”

Clinical importance of aspirin and clopidogrel resistance

“…In particular, it has been suggested that this interaction is more likely with lipophilic statins, which share the same CYP450 metabolizing isoenzyme (Table 1 [66][67][68][69][70][71][72] ). However, discordance between ex vivo data, which points in favour of an interaction, and the majority of clinical studies, which failed to detect a clinically relevant effect, has to be acknowledged [72] . Lau et al [73] reiterated the contribution of CYP3A4 activity to the phenomenon of clopidogrel resistance.…”

Clinical evidence of interaction between clopidogrel and proton pump inhibitors

“…There is some evidence to support a possible pharmacokinetic interaction between statins and clopidogrel. However, real-life interactions including hard end point studies seem to lack an association between the two drugs [57] . The United States FDA, on November 17, 2009, updated the public and health care professions about new safety information concerning a drug interaction between omeprazole and clopidogrel.…”