The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel

Gladding, Patrick; Webster, Mark; Zeng, Irene; Farrell, Helen; Stewart, Jim; Ruygrok, P.; Ormiston, John; El‐Jack, Seif; Armstrong, Guy; Kay, Patrick; Scott, Douglas; Gunes, Arzu; Dahl, Marja­‐Liisa

doi:10.1016/j.jcin.2008.09.005

Cited by 52 publications

(10 citation statements)

References 29 publications

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“…The patients diagnosed as hyporesponders (55.6%) were changed to 150 mg/day clopidogrel and experienced a decrease in mean platelet reactivity from 62 to 49.4% after 15 days (p < 0.001). Furthermore, results from the PRINC trial examined the effect of differing clopidogrel regimens on platelet inhibition in patients undergoing PCI [28]. A second 600-mg loading dose 2 h after the first produced better acute platelet inhibition (42% inhibition with clopidogrel vs. 24% with placebo).…”

Section: Management Strategies For Patients With the Cyp 2c19*2 Polymmentioning

confidence: 99%

“…A second 600-mg loading dose 2 h after the first produced better acute platelet inhibition (42% inhibition with clopidogrel vs. 24% with placebo). The trial also demonstrated that an increased maintenance dose of 150 mg produced superior platelet inhibition after 1 week compared to 75 mg in clopidogrel hyporesponders [28]. …”

Section: Management Strategies For Patients With the Cyp 2c19*2 Polymmentioning

confidence: 99%

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Genetic Determinations of Variable Responsiveness to Clopidogrel and Implications for Neurointerventional Procedures

Colley

Yan

2012

Intervent Neurol

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Endovascular intervention is emerging as a substitute for open surgical procedures for the treatment of cerebrovascular disease. However, up to 9% of patients undergoing neurointerventional procedures develop thromboembolic complications. Strategies to reduce periprocedural thromboembolic events are dominated by the use of dual antiplatelet therapy (DAT) which has been validated based on studies of peripheral vascular and coronary intervention. Of note, DAT decreases adverse vascular outcomes by 75–80% in patients undergoing percutaneous coronary intervention (PCI). It follows that similar treatment effects would be observed in neurointerventional populations. However, a growing body of evidence demonstrates that a subgroup of patients respond suboptimally to DAT, and in particular to clopidogrel (termed clopidogrel hyporesponders). These patients may be at an increased risk of thromboembolic complications such as in-stent thrombosis following neurointerventional procedures. Previous studies report 5–30% suboptimal response to clopidogrel in the cardiovascular population, while a higher prevalence is seen in populations undergoing neurointerventional procedures, i.e. as much as 66%. Knowledge of the mechanism leading to clopidogrel hyporesponsiveness is accumulating. A number of genetic polymorphisms, in particular CYP 2C19*2, have been associated with clopidogrel hyporesponsiveness and clinical outcomes. In addition, there are significant differences in the prevalence of CYP 2C19*2 across racial groups. Approximately 50% of Asians and 25% of Caucasians harbor the CYP 2C19*2 allele. While no prospective randomized trials currently exist to demonstrate improved clinical outcomes with genotype-based treatment for carriers of the CYP 2C19*2 polymorphism, a number of studies show that an increased dose of clopidogrel improves platelet inhibition in hyporesponders. The aim of the review is to examine the current understanding of the genetic basis of clopidogrel hyporesponsiveness in patients undergoing neurointerventional procedures and to explore current efforts using genotype and phenotype testing as well as alternative strategies to overcome the clopidogrel hyporesponsiveness.

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Section: Management Strategies For Patients With the Cyp 2c19*2 Polymmentioning

confidence: 99%

Section: Management Strategies For Patients With the Cyp 2c19*2 Polymmentioning

confidence: 99%

Genetic Determinations of Variable Responsiveness to Clopidogrel and Implications for Neurointerventional Procedures

Colley

Yan

2012

Intervent Neurol

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“…39,40 Moreover, a recent study suggested that patients with two loss-of-function CYP2C19 alleles and HPR on therapy were less responsive to dose escalation, and might represent a population that requires non-CYP2C19 dependent P2Y12 inhibition. 41,42 Cilostazol has been evaluated in carriers of CYP2C19 polymorphisms, and though a reduced incidence of HPR can be achieved, the clinical relevance of a pharmacogenomics strategy has yet to be determined. 43 …”

Section: Antiplatelet Therapymentioning

confidence: 99%

Personalized vascular medicine: Individualizing drug therapy

et al. 2011

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Personalized medicine refers to the application of an individual’s biological fingerprint – the comprehensive dataset of unique biological information – to optimize medical care. While the principle itself is straightforward, its implementation remains challenging. Advances in pharmacogenomics as well as functional assays of vascular biology now permit improved characterization of an individual’s response to medical therapy for vascular disease. This review describes novel strategies designed to permit tailoring of four major pharmacotherapeutic drug classes within vascular medicine: antiplatelet therapy, antihypertensive therapy, lipid-lowering therapy, and antithrombotic therapy. Translation to routine clinical practice awaits the results of ongoing randomized clinical trials comparing personalized approaches with standard of care management.

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“…The latter have been identified as a high risk subset, with as much as a 6.7-fold increase in the 30-day risk of composite death, myocardial infarction, or revascularization in those undergoing PCI (Hochholzer et al, 2006). In patients with HPR, clopidogrel dose escalation can incrementally reduce platelet activity and decrease the incidence of HPR from 37 to 14% ( p = 0.002; Gladding et al, 2008). However, whether HPR should dictate subsequent therapy is unclear.…”

Section: Aspirin and P2y12 Inhibitorsmentioning

confidence: 99%

Emerging Therapies for Acute Coronary Syndromes

Lilly¹,

Wilensky²

2011

Front. Pharmacol.

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In the majority of cases acute coronary syndromes (ACS) are caused by activation and aggregation of platelets and subsequent thrombus formation leading to a decrease in coronary artery blood flow. Recent focus on the treatment of ACS has centered on reducing the response of platelets to vascular injury as well as inhibiting fibrin deposition. Novel therapies include more effective P2Y12 receptor blockers thereby reducing inter-individual variability, targeting the platelet thrombin receptor (protease activated receptor 1) as well as directly inhibiting factor Xa or thrombin activity. In this review we discuss the clinical data evaluating the effectiveness of these various new ACS treatment options.

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The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel

Cited by 52 publications

References 29 publications

Genetic Determinations of Variable Responsiveness to Clopidogrel and Implications for Neurointerventional Procedures

Genetic Determinations of Variable Responsiveness to Clopidogrel and Implications for Neurointerventional Procedures

Personalized vascular medicine: Individualizing drug therapy

Emerging Therapies for Acute Coronary Syndromes

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