Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention

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Abstract

Background: Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods: Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results: Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16–24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37–2.8). Conclusion: High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalClinical Pharmacology: Advances and Applications
Volume8
DOIs
StatePublished - Jun 3 2016

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clopidogrel
Percutaneous Coronary Intervention
Blood Platelets
Platelet Aggregation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Adenosine Diphosphate
Control Groups
Atorvastatin Calcium
Cytochrome P-450 CYP3A

Keywords

  • Atorvastatin
  • Clopidogrel
  • Myocardial infarction
  • Percutaneous coronary intervention
  • Platelet aggregation

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

@article{411431a318af47138fb2635c0baf6ffd,
title = "Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention",
abstract = "Background: Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods: Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results: Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57{\%}±19{\%} vs 61{\%}±21{\%}; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37{\%}±18{\%} vs 39{\%}±21{\%}; P=0.72) and 16–24 hours post-clopidogrel loading dose (35{\%}±17{\%} vs 37{\%}±18{\%}; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95{\%} confidence interval 0.37–2.8). Conclusion: High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).",
keywords = "Atorvastatin, Clopidogrel, Myocardial infarction, Percutaneous coronary intervention, Platelet aggregation",
author = "Rolf Kreutz and Jeffrey Breall and Anjan Sinha and {von der Lohe}, Elisabeth and Richard Kovacs and Flockhart, {David A.}",
year = "2016",
month = "6",
day = "3",
doi = "10.2147/CPAA.S98790",
language = "English (US)",
volume = "8",
pages = "45--50",
journal = "Clinical Pharmacology: Advances and Applications",
issn = "1179-1438",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention

AU - Kreutz, Rolf

AU - Breall, Jeffrey

AU - Sinha, Anjan

AU - von der Lohe, Elisabeth

AU - Kovacs, Richard

AU - Flockhart, David A.

PY - 2016/6/3

Y1 - 2016/6/3

N2 - Background: Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods: Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results: Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16–24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37–2.8). Conclusion: High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).

AB - Background: Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. Methods: Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16–24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. Results: Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16–24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37–2.8). Conclusion: High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).

KW - Atorvastatin

KW - Clopidogrel

KW - Myocardial infarction

KW - Percutaneous coronary intervention

KW - Platelet aggregation

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U2 - 10.2147/CPAA.S98790

DO - 10.2147/CPAA.S98790

M3 - Article

AN - SCOPUS:84992021237

VL - 8

SP - 45

EP - 50

JO - Clinical Pharmacology: Advances and Applications

JF - Clinical Pharmacology: Advances and Applications

SN - 1179-1438

ER -