 |
|
Absence of Interaction Between Atorvastatin or Other Statins and Clopidogrel
Results From the Interaction Study
Victor L. Serebruany, MD, PhD;
Mark G. Midei, MD;
Alex I. Malinin, MD;
Benjamin R. Oshrine, BS;
David R. Lowry, MPH, DrPH;
David C. Sane, MD;
Jean-François Tanguay, MD;
Steven R. Steinhubl, MD;
Peter B. Berger, MD;
Christopher M. O'Connor, MD;
Charles H. Hennekens, MD
Arch Intern Med. 2004;164:2051-2057.
Background Some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to address this issue prospectively by performing serial measurements of 19 platelet characteristics using conventional aggregometry, rapid analyzers, and flow cytometry.
Methods The Interaction of Atorvastatin and Clopidogrel Study (Interaction Study) was designed for patients undergoing coronary stenting. All patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg of clopidogrel immediately prior to stent implantation. They had been taking atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at least 30 days prior to stenting. The main outcome measure was comparison of platelet biomarkers 4 and 24 hours after clopidogrel administration between study groups.
Results At baseline, patients from both statin groups exhibited diminished platelet aggregation and reduced platelet expression of G–protein-coupled protease-activated thrombin receptor (PAR)-1. There were no significant differences in measured platelet characteristics among the study groups 4 and 24 hours after clopidogrel intake, with the exception of a lower collagen-induced aggregation at 24 hours and a constantly diminished expression of PAR-1 in patients treated with any statin.
Conclusions Statins in general, and atorvastatin in particular, do not affect the ability of clopidogrel to inhibit platelet function in patients undergoing coronary stenting. These prospective data also suggest that statins may inhibit platelets directly via yet unknown mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.
From the HeartDrug Research, LLC, Baltimore, Md (Drs Serebruany and Malinin and Mr Oshrine); Midatlantic Cardiovascular Associates (Drs Midei and Lowry); Wake Forest University, Winston-Salem, NC (Dr Sane); Montreal Heart Institute, Montreal, Quebec (Dr Tanguay); University of North Carolina at Chapel Hill (Dr Steinhubl); Duke Clinical Research Institute, Durham, NC (Drs Berger and O'Connor), and the University of Miami, Miami, Fla (Dr Hennekens). Dr Hennekens is now also with the Agatston Research Institute. Dr Steinhubl has received research support from and is a consultant for Brisol-Myers Squibb/Sanofi; Dr O'Connor is a consultant for Bristol-Myers Squibb/Sanofi, Merck, and Pfizer; Dr Hennekens is a consultant for AstraZeneca, Bristol-Myers Squibb/Sanofi, Novartis, Pfizer, and Reliant. This study was funded by a grant from Pfizer Inc, New York, NY.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Interaction between statins and clopidogrel: is there anything clinically relevant?
Bhindi et al.
QJM 2008;101:915-925.
ABSTRACT
| FULL TEXT
Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy
Geisler et al.
Eur Heart J 2008;29:1635-1643.
ABSTRACT
| FULL TEXT
Prevalence and Risk Factors for Aspirin and Clopidogrel Resistance in Cerebrovascular Stenting
Prabhakaran et al.
Am. J. Neuroradiol. 2008;29:281-285.
ABSTRACT
| FULL TEXT
Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study
Gilard et al.
J Am Coll Cardiol 2008;51:256-260.
ABSTRACT
| FULL TEXT
Lack of Evidence of a Clopidogrel Statin Interaction in the CHARISMA Trial
Saw et al.
J Am Coll Cardiol 2007;50:291-295.
ABSTRACT
| FULL TEXT
Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease
Maree and Fitzgerald
Circulation 2007;115:2196-2207.
FULL TEXT
Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives
Angiolillo et al.
J Am Coll Cardiol 2007;49:1505-1516.
ABSTRACT
| FULL TEXT
Acute coronary syndromes, response to clopidogrel, and worsened cardiovascular outcomes: the hen and the egg dilemma
Serebruany
Eur Heart J 2007;28:640-641.
FULL TEXT
Aspirin and Clopidogrel Resistance
Fitzgerald and Maree
ASH Education Book 2007;2007:114-120.
ABSTRACT
| FULL TEXT
Clopidogrel-Precipitated Rhabdomyolysis in a Stable Heart Transplant Patient
Burton et al.
The Annals of Pharmacotherapy 2007;41:133-137.
ABSTRACT
| FULL TEXT
Clopidogrel Response Variability and Future Therapies: Clopidogrel: Does One Size Fit All?
O'Donoghue and Wiviott
Circulation 2006;114:e600-e606.
FULL TEXT
Drug interactions in the setting of acute coronary syndromes and dual anti-platelet therapy
Bassand
Eur Heart J Suppl 2006;8:G35-G37.
ABSTRACT
| FULL TEXT
Understanding clopidogrel efficacy in the presence of cytochrome P450 polymorphism
Turgeon et al.
CMAJ 2006;174:1729-1729.
FULL TEXT
Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study.
Serebruany et al.
Postgrad. Med. J. 2006;82:404-410.
ABSTRACT
| FULL TEXT
Aspirin and clopidogrel resistance: an emerging clinical entity
Wang et al.
Eur Heart J 2006;27:647-654.
ABSTRACT
| FULL TEXT
Clopidogrel Resistance: Myth or Reality?
Barsky and Arora
J CARDIOVASC PHARMACOL THER 2006;11:47-53.
ABSTRACT
Effects of Clopidogrel and Aspirin in Combination Versus Aspirin Alone on Platelet Activation and Major Receptor Expression in Patients After Recent Ischemic Stroke: For the Plavix Use for Treatment of Stroke (PLUTO-Stroke) Trial
Serebruany et al.
Stroke 2005;36:2289-2292.
ABSTRACT
| FULL TEXT
Resistance to clopidogrel: A review of the evidence
Nguyen et al.
J Am Coll Cardiol 2005;45:1157-1164.
ABSTRACT
| FULL TEXT
|
