The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel: The Plavix Response in Coronary Intervention (Princ) Trial

Gladding, PA; Webster, M.W.I.; Zeng, Irene; Stewart, Jim; Ruygrok, P.; Ormiston, John; El‐Jack, Seif; Armstrong, Guy; Kay, Patrick; Scott, Douglas

doi:10.1016/j.hlc.2008.03.037

Cited by 17 publications

(21 citation statements)

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“…25 It was reported recently that 225 mg clopidogrel in CYP2C19*2 heterozygotes resulted in comparable platelet inhibition compared with standard 75 mg dose in noncarriers. However, in CYP2C19*2 homozygotes, even 300 mg clopidogrel did not result in comparable degrees of platelet inhibition compared with standard 75 mg dose in noncarriers.…”

Section: Discussionmentioning

confidence: 98%

CYP2C19 Poor Metabolizer Is Associated With Clinical Outcome of Clopidogrel Therapy in Acute Myocardial Infarction But Not Stable Angina

Kim

Chang

Koh

et al. 2013

Circ Cardiovasc Genet

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C lopidogrel on top of aspirin improves clinical outcomes in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention (PCI). 1 Although clopidogrel has been extensively prescribed, interindividual variation in clinical responses has fueled research into personalized pharmacotherapy for patients undergoing drug-eluting stent (DES) implantation.2,3 Clopidogrel has to be biotransformed into its active thiol metabolite to exert its antiplatelet effects; this is accomplished by hepatic cytochrome P450 isoenzymes such as CYP2C19. 4 The CYP2C19 loss-of-function (LOF) alleles (*2 and *3 alleles) result in less formation of active thiol metabolite, causing lack of platelet aggregation inhibition, which translates into a higher rate of subsequent cardiovascular events than noncarriers. Background-More intensive platelet suppression is required in patients with acute myocardial infarction (AMI) than in those with stable angina because of differential platelet activation between AMI and stable angina. In this context, CYP2C19 genotype leading to reduced active metabolite formation may profoundly affect the clinical outcome of clopidogrel therapy in patients with AMI compared with those with stable angina. Methods and Results-Effects of CYP2C19 genotypes on the clinical outcome of clopidogrel therapy were evaluated in 2188 patients (532 patients with AMI and 1656 patients with stable angina) undergoing percutaneous coronary intervention. The primary clinical outcome was a composite of major adverse cardiac and cerebrovascular events defined as death from any cause, nonfatal myocardial infarction, or stroke during 1 year of clopidogrel therapy. Compared with extensive metabolizer, the CYP2C19 poor metabolizer was significantly associated with higher risk of major adverse cardiac and cerebrovascular events in patients with AMI (hazard ratio, 2.88; 95% confidence interval, 1.27-6.53; P=0.011). However, this finding was not seen in patients with stable angina. A significant interaction between CYP2C19 genotypes and disease subsets of AMI and stable angina was identified with respect to major adverse cardiac and cerebrovascular events (adjusted interaction P=0.045). The patients with AMI showed lower percent inhibition of P2Y12 compared with patients with stable angina in CYP2C19 poor metabolizer or CYP2C19 intermediate metabolizer genotype groups but not in CYP2C19 extensive metabolizer genotype group. Conclusions-CYP2C19 poor metabolizer is associated with poor clinical outcome of clopidogrel therapy in Asian patients with AMI but not in those with stable angina possibly because of differential requirement of platelet suppression in patients with AMI and stable angina.

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Section: Discussionmentioning

confidence: 98%

CYP2C19 Poor Metabolizer Is Associated With Clinical Outcome of Clopidogrel Therapy in Acute Myocardial Infarction But Not Stable Angina

Kim

Chang

Koh

et al. 2013

Circ Cardiovasc Genet

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“…There are few data on the inhibitory effect of alternative dosing regimens in CYP2C19 intermediate and/or poor metabolizers. Several studies have evaluated the effect of different combinations of clopidogrel LDs and MDs on platelet aggregation, metabolites of clopidogrel, and other measures of platelet function [32][33][34][35][36][37][38][39][40][41] (Table 2). Some studies were performed specifically in patients with a documented suboptimal response to the usual dosing protocols for clopidogrel.…”

Section: Alternative Dosing Regimens For Clopidogrelmentioning

confidence: 99%

“…In general, a 600-mg LD or double LD (second 600-mg dose 2 hours later) improves the degree of acute platelet inhibition. 33,37 Moreover, an MD of 150 mg daily results in a greater degree of platelet inhibition in many studies in patients with a reduced response to the usual 75-mg MD. 36 -38 However, even at the higher dose, some patients do not reach an optimal level of platelet inhibition ex vivo.…”

Section: Alternative Dosing Regimens For Clopidogrelmentioning

confidence: 99%

ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning”

Holmes¹,

Dehmer²,

Kaul³

et al. 2010

Circulation

198

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“…Altered clopidogrel dosing strategies have been associated with improved platelet responsiveness in 2 recent trials. 37,38 Alternatively, a more uniformly effective thienopyridine (prasugrel) may be able to reduce ST events compared with clopidogrel, both for early ST and between 30 days and 15 months. 39 Optimal DAPT duration will be examined further in a large (Ͼ20 000 patients) industry-sponsored study to evaluate the comparative benefits of 30 versus 12 months of DAPT, in DES and propensity-matched BMS patients.…”

Section: Lasala Et Al Stent Thrombosis In Arrive Registry Programmentioning

confidence: 99%

Drug-Eluting Stent Thrombosis in Routine Clinical Practice

Lasala

Cox

Dobies

et al. 2009

Circ: Cardiovascular Interventions

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for the ARRIVE 1 and ARRIVE 2 Participating Physicians Background-Stent thrombosis (ST) is an uncommon but serious complication of drug-eluting and bare metal stents.To assess drug-eluting stent ST in contemporary practice, we analyzed 2-year data from the 7492-patient ARRIVE registry. Methods and Results-Patients were enrolled at the initiation of percutaneous coronary intervention with no inclusion/ exclusion criteria beyond use of the paclitaxel-eluting TAXUS stent. Two-year follow-up was 94% with independent adjudication of major cardiac events.

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The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel: The Plavix Response in Coronary Intervention (Princ) Trial

Cited by 17 publications

References 0 publications

CYP2C19 Poor Metabolizer Is Associated With Clinical Outcome of Clopidogrel Therapy in Acute Myocardial Infarction But Not Stable Angina

CYP2C19 Poor Metabolizer Is Associated With Clinical Outcome of Clopidogrel Therapy in Acute Myocardial Infarction But Not Stable Angina

ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning”

Drug-Eluting Stent Thrombosis in Routine Clinical Practice

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