Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention

Lev, Eli I.; Patel, Rajnikant; Maresh, Kelly; Guthikonda, Sasidhar; Granada, Juan F.; DeLao, Timothy; Bray, Paul F.; Kleiman, Neal S.

doi:10.1016/j.jacc.2005.08.058

Cited by 415 publications

(269 citation statements)

References 30 publications

(39 reference statements)

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“…Quantitative coronary angiography and PCI data. different studies [11][12][13]. This wide ranging variability is probably due to the lack of a standardized definition of the term "clopidogrel resistance".…”

Section: Discussionmentioning

confidence: 99%

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

Abid¹,

Laroussi²,

Bahloul³

et al. 2013

WJCD

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Introduction: The concept of clopidogrel resistance, first described in biology is being strengthened by recent data from clinical epidemiology. The cardiologists have been sensitized to this concept because of its possible involvement in the occurrence of coronary stent thrombosis. Purpose of the study: The purpose of this study was to investigate the genetic variant of the gene CYP 2C19 in our population and to assess the involvement of this genetic profile in the occurrence of major cardiovascular events (MACE) during the follow-up period. Methods: Our prospective study was conducted between May 2009 and September 2010 including 100 patients admitted to the cardiology department for percutaneous coronary stenting. The patients were divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and noncarriers. Results: The mean age of our patients was 56.7 years ± 10, 5. No remarkable differences in the baseline characteristics were noted between the two groups. The prevalence of CYP2C19*2 allele in our population was 11.5%. Hospital mortality was estimated at 3%. No statistically significant differences were noted between the two groups regarding the occurrence of intra hospital MACE. The mean follow up was 7.5 ± 4.87 months for the entire study population. The rate of MACE during the follow-up of patients receiving clopidogrel was 8.2% throughout the study population: 5.3% in the *2 non-carriers versus 18.2% in the *2 carriers with a statistically significant difference (p = 0.075) at the risk of error of 10%. Concerning the occurrence of stent thrombosis, there was no significant statistical difference between the two study groups. Conclusion: From these results it is suggested that CYP2C19*2 polymorphism is associated with increase in the occurrence of MACE among Tunisian patients receiving clopidogrel. A larger study is needed to assess the role of genotyping in the evaluation of the phenomenon of clopidogrel resistance.

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Section: Discussionmentioning

confidence: 99%

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

Abid¹,

Laroussi²,

Bahloul³

et al. 2013

WJCD

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“…Clopidogrel resistance is estimated to occur in 4% and 41% of patients. 36,37 Among patients undergoing elective PCI, in 1 cohort it was estimated that nearly 50% of aspirin-resistant patients were also resistant to clopidogrel. In patients with dual antiplatelet resistance, there was nearly a 3-fold increase in the incidence of myonecrosis following PCI compared to dual-sensitive patients.…”

Section: Mechanisms Of Aspirin Resistancementioning

confidence: 99%

“…In patients with dual antiplatelet resistance, there was nearly a 3-fold increase in the incidence of myonecrosis following PCI compared to dual-sensitive patients. 36 Similarly, among patients who have developed stent thrombosis, 43% of patients were resistant to both aspirin and clopidogrel compared to 14% of controls. 38 Aspirin-resistant patients appear to have platelets that are more sensitive to ADP, which may partially explain the high prevalence of dualantiplatelet resistance in this population.…”

Section: Mechanisms Of Aspirin Resistancementioning

confidence: 99%

Aspirin Resistance: Current Status and Role of Tailored Therapy

Grinstein

Cannon

2012

Clinical Cardiology

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Aspirin is integral in the primary and secondary prevention of coronary artery disease and acute coronary syndrome. Given the high clinical importance of aspirin in the management of coronary artery disease, much attention has been directed towards the concept of “aspirin resistance.” Unfortunately, the term aspirin resistance is ill‐defined in the literature, leading to a large variance in the reported prevalence of this phenomenon. In this review, the current understanding of aspirin resistance is discussed. Commonly used functional and diagnostic tests of platelet function, including their strengths and weakness, are reviewed. We next discuss several proposed mechanisms of aspirin resistance and special high‐risk groups at risk for aspirin treatment failure. We then discuss optimal dosing and diagnostic strategies for those populations at risk for aspirin resistance with a focus on tailored aspirin therapy for high‐risk groups. Finally, future topics of interest in the field of aspirin resistance are considered. Clin. Cardiol. 2012 doi: 10.1002/clc.22031Jonathan Grinstein has no funding, financial relationships, or conflicts of interest to disclose. Christopher P. Cannon receives research grants/support from the following companies: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda. He is also on the advisory board (but funds donated to charity) for Alnylam, Bristol‐Myers Squibb, and Pfizer. He is a Clinical Advisor, equity in Automedics Medical Systems.

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“…42 Immediately after PCI, patients received 300 mg clopidogrel and 325 mg ASA, followed by 75 mg clopidogrel and 325 mg ASA daily. Hyporesponse ASA was defined as having 2 or 3 of the following criteria: rapid platelet function analyzer-ASA score 500, 5µmol/L ADP-induced aggregation 70%, and 0.5 mg/mL arachidonic acid-induced aggregation 20%.…”

Section: Hyporesponsiveness To Dual Antiplatelet Therapymentioning

confidence: 99%

“…Patients who were hyporesponsive to dual agents had a 2-fold increase in the rate of myonecrosis versus dual drug-sensitive patients. 42 …”

Section: Hyporesponsiveness To Dual Antiplatelet Therapymentioning

confidence: 99%

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

et al. 2008

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Hyporesponsiveness, or resistance, to antiplatelet therapy may be a major contributor to poorer outcomes among cardiac patients and may be attributed to an array of mechanisms—both modifiable and unmodifiable. Recent evidence has uncovered clinical, cellular, and genetic factors associated with hyporesponsiveness. Patients with severe acute coronary syndromes (ACS), type 2 diabetes, and increased body mass index appear to be the most at risk for hyporesponsiveness. Addressing modifiable mechanisms may offset hyporesponsiveness, while recognizing unmodifiable mechanisms, such as genetic polymorphisms and diseases that affect response to antiplatelet therapy, may help identify patients who are more likely to be hyporesponsive. Hyporesponsive patients might benefit from different dosing strategies or additional antiplatelet therapies. Trials correlating platelet function test results to clinical outcomes are required. Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness. Copyright © 2008 Wiley Periodicals, Inc.

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Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention

Abstract: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.

Cited by 415 publications

References 30 publications

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

Impact of cytochrome P450 2C19*2 polymorphism on the clinical cardiovascular events after stent implantation in patients receiving clopidogrel of a southern Tunisian region

Aspirin Resistance: Current Status and Role of Tailored Therapy

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

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