The inhibitory potency of clopidogrel on ADP-induced platelet activation is not attenuated when it is co-administered with atorvastatin (20 mg/day) for 5 weeks in patients with acute coronary syndromes

Abstract

The antiplatelet potency of clopidogrel may be attenuated by short-term co-administration of lipophilic statins metabolized through the cytochrome P-450, isoform 3A4. We investigated whether the co-administration of atorvastatin (20?mg/day) for 5 weeks, in patients with acute coronary syndromes (ACS) could affect the antiplatelet activity of clopidogrel. Fifty-one patients with the first episode of an ACS were included in the study. All patients underwent percutaneous coronary intervention (PCI) and received a loading dose of 375 mg of clopidogrel, followed by 75 mg/day for at least 3 months. Twenty-six of them presented with low density lipoprotein (LDL) cholesterol levels >100?mg/dl (2.6 mmol/l) (measured within 24 h from the onset of symptoms) and received daily 20 mg/day of atorvastatin. The ADP- or TRAP-induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 min after admission) and 5 weeks afterwards. Atorvastatin did not influence either the clopidogrel-induced inhibition of platelet aggregation initiated by 5 or 10 microM ADP or the clopidogrel-induced reduction of the membrane expression of P-selectin and CD40L induced by ADP. In conclusion, atorvastatin, even at a dose of 20 mg/day does not affect the antiplatelet efficacy of clopidogrel when co-administered for 5 weeks in ACS patients.

Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel

“…Some studies suggested that lipophilic statins (atorvastatin, lovastatin, and simvastatin) may competitively inhibit CYP3A4 and decrease the generation of clopidogrel's active metabolite, reducing the antiplatelet effect of clopidogrel (7,39,40). On the contrary, other reports were not able to confirm this findings (41)(42)(43)(44)(45)(46). Similarly, we did not observe any drug-drug interaction between clopidogrel and lipophilic statins as measured with both assays in the current study.…”

Possible mechanisms of drug-induced aspirin and clopidogrel resistance

“…The objective of this was an assessment of higher doses of atorvastatin on clopidogrel's platelet inhibition [54]. Clopidogrel was given as a 375-mg loading dose followed by 75 mg/day for at least 3 months and platelet function was assessed at baseline and at 5 weeks by using several measures including ADPstimulated aggregation, P-selectin (CD62P) expression, and CD40L expression.…”

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

“…Clopidogrel is mainly metabolized into its active metabolite via cytochrome P-450 3A4; however, upregulation of cytochrome P-450 2B6, 2C19 could compensate for decreased activity of cytochrome P-450 3A4 during clopidogrel and atorvastatin co-administation, even in the early stage. 5,23 Although the lipid profiles were more favorable in the ATOR40 Group regarding the LDL-C and TC concentrations, no significant differences were found in reducing late lumen loss and inflammatory markers, such as IL-6, TNF-α, sICAM-1, sVCAM-1 and hs-CRP, compared with the ATOR10 Group. This might be because other medications, such as angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, were administered during the study.…”

“…20 However, others have suggested that atorvastatin does not influence the antiplatelet effect of clopidogrel. 3,5,21 Many clinicians were confused by these controversial results and questioned the safety of clopidogrel and atorvastatin co-administration in "real world" clinical practice. Large clinical trials have answered this question about safety; for example, the Clopidogrel for Reduction of Events During Observation (CREDO) trial demonstrated that there was no adverse effect on the 1-year clinical outcomes with clopidogrel and lipophilic statin co-administration.…”

“…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.…”