Comparison of Low vs Moderate Dose of Atorvastatin in Clopidogrel Resistance After Coronary Stenting in Korean Patients With Acute Coronary Syndrome

Abstract

torvastatin metabolized by cytochrome P450 3A4reportedly reduces the metabolism of clopidogrel to its active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. Atorvastatin and clopidogrel interaction increased the risk of recurrent atheroembolic events in some reports, 1,2 whereas others have reported the controversial result that atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly. [3][4][5][6] Clopidogrel resistance is a strong predictor of stent thrombosis in patients with drug-eluting stent (DES) implantation, 7,8 and could be life-threatening, especially in patients with acute coronary syndrome (ACS), after DES implantation. ACS continues to be a major public health problem, even with the advances in medical technologies in the modern era. 9 Atorvastatin is 1 of the most prescribed statins in Korea, and the long-term combined use of clopidogrel with atorvastatin 10 mg (low-dose) or 40 mg (moderate-dose) has been increasing after the introduction of DES in Korea. In the present study, atorvastatin 40 mg, instead of 80 mg, was compared with atorvastatin 10 mg because atorvastatin 80 mg is not frequently used in Korea unlike in Western countries. If the use of 10 or 40 mg atorvastatin reduces the platelet-inhibiting effect of clopidogrel in patients with ACS, it could be a serious medical problem after DES implantation. The purpose of this prospective, randomized, single-blinded, investigator-initiated 8 month follow-up study was to compare the effect of the 2 doses of atorvastatin in cases of clopidogrel resistance and the clinical events after sirolimus-eluting stent (SES) implantation in Korean patients with ACS. Methods Study PatientsPatients aged 35-75 years with ACS requiring stent implantation were eligible for participation in the study and after SES implantation they were prospectively included in the study at Korea University Anam Hospital cardiovascular centers from July 2005 through June 2007. A total of 322 patients were screened for inclusion in the study; 192 who did not fulfill the inclusion criteria or who had any of the exclusion criteria were excluded. The eligible patients (n=130: 49 women, 81 men) were randomly assigned to receive either atorvastatin 10 mg (ATOR10 Group, 65 patients, 85 lesions) or atorvastatin 40 mg (ATOR40 Group, 65 patients, 93 lesions) (Figure 1), co-administered with 300 mg of clopidogrel on admission and 75 mg/day of clopidogrel maintained thereafter. Aspirin and clopidogrel were maintained in all patients during the 8-month follow-up. Beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers were added when needed. Patients with unstable angina pectoris (UAP), non-ST elevation myocardial infarction (MI), and ST-elevation MI pre- (Received December 2, 2008; revised manuscript received January 4, 2009; accepted January 28, 2009; released online April 17, 2009 5±7.8 (4 h, 24 h, 5 days, and 8 months, respectively, after 300 mg of clopidogrel pretreatment) ...

Effect of Atorvastatin and Clopidogrel Co-Administration After Coronary Stenting in Korean Patients With Stable Angina

“…Furthermore, concomitant prescription of statins with clopidogrel is common worldwide in patients who undergo percutaneous coronary intervention, but there have been few reports on the impact of co-administering statins and clopidogrel on the anti-platelet activity of clopidogrel in Asians. Recently, Hong et al23) demonstrated no significant differences in anti-platelet potency of clopidogrel when it was co-administered with 10 mg or 40 mg of atorvastatin for eight months in patients with acute coronary syndrome 23)…”

Άμεση Έναντι Καθυστερημένης Αγγειοπλαστική Των Στεφανιαίων Αρτηριών Μετά Φόρτιση Με Υψηλή Δόση Κλοπιδογρέλης

“…Οι συγκεκριμένες στατίνες ανταγωνίζονται τη σύνδεση της κλοπιδογρέλης στο κυττόχρωμα P προκαλώντας ελαττωμένη βιομετατροπή της στο ήπαρ. Μεταγενέστερες ερευνητικές εργασίες απέκλεισαν την ύπαρξη σημαντικής αλληλεπίδρασης μεταξύ των συγκεκριμένων φαρμάκων [88][89][90][91][92]. Η συγχορήγηση λιπόφιλων στατινών και κλοπιδογρέλης θεωρείται δόκιμη.…”