Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Sharma, Rakesh; Erickson, Stephen W.; Sharma, Rohit K.; Voelker, Donald J.; Reddy, Hanumanth K.; Dod, Harvinder S.; Marsh, James D.

doi:10.2147/vhrm.s43909

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…However, although the rate of female patients in the CR+ group was higher than the rate of female patients in the CR-group, no significant relationship was found between CR and gender (Table 1). When the mean age was examined, no significant difference was found between the CR+ and CR-groups in support of previous studies (17,18).…”

Section: Discussionsupporting

confidence: 87%

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Clopidogrel Resistance in Stroke Cases

Çarçak¹,

Özmen²,

Dartıcı³

et al. 2019

Istanbul Med J

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Introduction Platelets (PLTs) play an essential role in the development of ischemic stroke in terms of pathophysiology of thrombosis formation (1). Clopidogrel, an antithrombotic agent that inhibits PLT activation via adenosine diphosphate (ADP), has proven efficacy and safety in preventing recurrent ischemic strokes (1). Clopidogrel is a secondgeneration thienopyridine derivative prodrug and is converted to its active metabolite by cytochrome P450 enzyme system (mainly CYP2C19)

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Section: Discussionsupporting

confidence: 87%

“…Studies have reported higher CR in women (17,18). However, although the rate of female patients in the CR+ group was higher than the rate of female patients in the CR-group, no significant relationship was found between CR and gender (Table 1).…”

Section: Discussionmentioning

confidence: 87%

Clopidogrel Resistance in Stroke Cases

Çarçak¹,

Özmen²,

Dartıcı³

et al. 2019

Istanbul Med J

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“…It has previously been reported that high platelet reactivity (HPR) on clopidogrel treatment is more frequent in AA thus increasing the risk of in-stent restenosis and progression of atherosclerotic disease. 15 On the other hand, HPR might also contribute to reduce the bleeding events in AA patients. The rate of bleeding events in AA patients after PCI might therefore be underestimated compared to non-AA who are more likely to respond to clopidogrel.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, there was a preferential use of clopidogrel in AA. It has previously been reported that high platelet reactivity (HPR) on clopidogrel treatment is more frequent in AA thus increasing the risk of in‐stent restenosis and progression of atherosclerotic disease . On the other hand, HPR might also contribute to reduce the bleeding events in AA patients.…”

Section: Discussionmentioning

confidence: 99%

Use of prasugrel and clinical outcomes in African‐American patients treated with percutaneous coronary intervention for acute coronary syndromes

Faggioni

Baber

Chandrasekhar

et al. 2019

Cathet Cardio Intervent

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Objective To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). Background AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. Methods Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self‐reported AA or other races. Clinical outcomes at 90‐day and 1‐year included non‐fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. Results The study population included 2,125 (11%) AA and 17,707 (89%) non‐AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non‐AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non‐AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non‐AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37–0.49], P < 0.0001). AA race was independently associated with a significantly higher risk of MI at 90‐days and 1 year after PCI. Conclusions Despite higher risk clinical presentation and worse 1‐year ischemic outcomes, AA race was an independent predictor of lower prasugrel prescription in a contemporary population of ACS patients undergoing PCI.

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“…1,[3][4][5][6] This is clinically significant because HPR is an independent risk factor for 12-month cardiovascular death and nonfatal myocardial infarction (MI).…”

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confidence: 99%

Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease

Waksman

Maya

Angiolillo

et al. 2015

Circ: Cardiovascular Interventions

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A cute coronary syndrome (ACS) is often the first manifestation of coronary artery disease (CAD). Current treatment for reducing thrombotic risk in patients with ACS includes antiplatelet agents, commonly aspirin (acetylsalicylic acid [ASA]) in combination with a P2Y 12 inhibitor. Metabolic activation of clopidogrel depends on multiple cytochrome P450 (CYP) enzymes, including CYP2C19, which can delay the onset of its activity; in addition, some individuals carry a reduced-function allele of the CYP2C19 gene, 1 leading to suboptimal conversion of prodrug to active metabolite and hyporesponse to clopidogrel. On-treatment platelet reactivity with this agent is therefore variable, and as this is partly genetically determined, it is influenced by ethnicity.1,2 Notably, the black population has a higher prevalence of the loss-of-function CYP2C19*2 allele and higher on-treatment platelet reactivity (HPR) compared with the white population. 1,[3][4][5][6] This is clinically significant because HPR is an independent risk factor for 12-month cardiovascular death and nonfatal myocardial infarction (MI).2 However, there is a paucity of data in black patients, who are often under-represented in clinical trials of antiplatelet agents.Ticagrelor is an orally administered, direct-acting, reversibly binding P2Y 12 receptor antagonist that inhibits adenosine diphosphate-induced platelet aggregation. 7,8 It has a unique mode of action (P2Y 12 inhibition and equilibrative nucleoside transporter 1 inhibition), 9,10 is rapidly absorbed, and has a rapid onset of action. Unlike clopidogrel, ticagrelor does not require biotransformation to an active state, although it is extensively metabolized by CYP3A4 and CYP3A5 to the major active metabolite AR-C124910XX. This metabolite is present at Background-The burden of coronary artery disease (CAD) is high in blacks, highlighting the need for clinical research of antiplatelet agents in this population. We sought to evaluate platelet reactivity during loading and maintenance dosing of ticagrelor versus clopidogrel, and the pharmacokinetic profile of ticagrelor and its metabolite AR-C124910XX, in black patients with stable CAD taking low-dose aspirin (acetylsalicylic acid). Methods and Results-In a multicenter, randomized, open-label, crossover study, 34 blacks with stable CAD receiving acetylsalicylic acid 75 to 100 mg/d were randomized to clopidogrel (600 mg, then 75 mg QD for 7-9 days) or ticagrelor (180 mg, then 90 mg BID for 7-9 days). After washout 10 to 14 days, patients switched regimens. 11 In comparative trials, ticagrelor has produced greater and more consistent inhibition of platelet aggregation than clopidogrel. 7,[12][13][14] In the phase III, Platelet Inhibition and Patient Outcomes (PLATO) trial, treatment with ticagrelor significantly reduced the rate of the primary composite end point of MI, stroke, or death from vascular causes compared with clopidogrel (9.8% versus 11.7%, respectively [hazard ratio, 0.84; 95% confidence interval, 0.77-0.92; P<0.001]).15 This benefit was prim...

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Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Cited by 11 publications

References 39 publications

Clopidogrel Resistance in Stroke Cases

Clopidogrel Resistance in Stroke Cases

Use of prasugrel and clinical outcomes in African‐American patients treated with percutaneous coronary intervention for acute coronary syndromes

Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease

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