Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel

Hochholzer, Willibald; Ruff, Christian T.; Mesa, Robert A.; Mattimore, John F.; Cyr, John F.; Lei, Lanyu; Frelinger, Andrew L.; Michelson, Alan D.; Berg, David D.; Angiolillo, Dominick J.; O’Donoghue, Michelle L.; Sabatine, Marc S.; Mega, Jessica L.

doi:10.1016/j.jacc.2014.03.051

Cited by 77 publications

(69 citation statements)

References 30 publications

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“…Other studies have demonstrated changes in platelet reactivity over time, mainly between 1 and 3 months after the index event. 7,8, 13 In line with those results, our study showed that, for both clopidogrel and prasugrel, the platelet reactivity varies significantly between discharge and 3 months, being more stable between 3 and 6 months. Moreover, the proportion of patients showing HPR status over time was higher using clopidogrel than prasugrel, likely as a reflection of the more constant effect of the novel thienopyridine.…”

Section: Discussionsupporting

confidence: 89%

“…This intra-individual variation was observed in the ELEVATE TIMI-56 trial in which approximately 11-15% of patients had a change in their responder status when tested at 2 different time points (each 14 days), even with higher clopidogrel doses. 13 Data coming from the Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents (ADAPT-DES) study suggest a considerable variation in the individual on-clopidogrel platelet reactivity, which was present in both the acute and subacute phases. 14 In addition, the platelet inhibition following the clopidogrel loading dose is higher during the early phase than in the follow-up.…”

Section: Discussionmentioning

confidence: 99%

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Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation

Tello‐Montoliu

Rivera

Hernández

et al. 2018

Circ J

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Background:Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described. Methods and Results:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA). By means of VN-P2Y12, prasugrel patients displayed significantly (P<0.001) higher platelet inhibition than clopidogrel patients over time, although there were not significant differences using MEA. Prasugrel patients showed higher platelet inhibition at baseline than at 3 months (59.3±8.1 vs. 105.0±49.2; P<0.001), without significant change at 6 months (107.9±72.0; P=0.919 vs. 3 months). Clopidogrel patients showed a similar trend (160.1±65.1, 184.8±62.7 and 185.0±53.3; baseline vs. 3 months P=0.060; 3 months vs. 6 months P=0.974). High platelet reactivity (HPR) was shown in 16.3% prasugrel patients, with no patient consistently remaining in HPR over time. HPR was detected in 36.6% of the clopidogrel patients, being consistently observed in 15.0% of them. Low platelet reactivity (LPR) was detected in 60.5% prasugrel and 9.8% clopidogrel patients. Conclusions:Prasugrel patients showed less temporal variation than patients on clopidogrel in terms of HPR. In contrast, higher variability in LPR was detected in prasugrel patients for up to 6 months' follow-up.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation

Tello‐Montoliu

Rivera

Hernández

et al. 2018

Circ J

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“…These results are concordant with those of a recent study reporting variable responses to clopidogrel among patients with coronary artery disease. 11 In healthy subjects, the mean and median VerifyNow values did not significantly differ when participants were tested 20 to 24 hours after the final dose of 80 mg to 325 mg of aspirin. 14 However, in contrast to healthy volunteers, patient populations at risk for arterial thrombosis have pathophysiologies that evoke variable intensities and mechanisms to stimulate platelets.…”

Section: Discussionmentioning

confidence: 84%

Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke

Kim

Heo

Choi

et al. 2015

Stroke

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Recently, time-dependent variability in platelet reactivity to clopidogrel has been detected in individuals with coronary artery disease.11 Thus, measuring platelet function at a single time point may not be sufficient to determine platelet reactivity in individual patients with acute ischemic stroke. Considering that the risk of recurrent stroke is the highest during the acute phase, 12 it is important to investigate the influence of platelet reactivity on early outcomes of acute ischemic stroke. Particularly, serial platelet reactivity assays may be useful for evaluating the association between early outcomes and platelet reactivity during unstable periods of acute ischemic stroke.Therefore, we sought to evaluate the individual variability in platelet reactivity of patients on aspirin during the acute stage after ischemic stroke and to determine the clinical Background and Purpose-Time-dependent changes in individual platelet reactivity have been detected in patients with coronary artery disease. Therefore, we sought to evaluate the time-dependent changes in platelet reactivity to aspirin during the acute stage after ischemic stroke and the clinical implications of variable patient responses to aspirin in acute ischemic stroke. Methods-We conducted a single-center, prospective, observational study. The acute aspirin reaction unit (ARU) was measured after 3 hours of aspirin loading, with higher values indicating increased platelet reactivity despite aspirin therapy. The follow-up ARU was measured on the fifth day of consecutive aspirin intake. The numeric difference between the follow-up ARU and the acute ARU was defined as ∆ARU and was stratified into quartiles. Early neurological deterioration was regarded as an early clinical outcome. Results-Both the acute ARU (476±69 IU) and the follow-up ARU (451±68 IU) were measured in 349 patients in this study. Early neurological deterioration was observed in 72 patients (20.6%). Changes in aspirin platelet reactivity over time showed an approximately Gaussian distribution. The highest ∆ARU quartile was independently associated with early neurological deterioration (odds ratio, 3.19; 95% confidence interval, 1.43-7.10; P=0.005) by multivariate logistic regression analysis. Conclusions-The results of our study showed that the increase in platelet reactivity to aspirin over time is independently associated with early neurological deterioration in patients with acute ischemic stroke. In addition, during the acute stage of ischemic stroke, serial platelet reactivity assays may be more useful than a single assay for identifying the clinical implications of aspirin platelet reactivity after ischemic stroke. Kim et al Changes in Platelet Reactivity in AIS 2535implications of this variability in platelet reactivity in acute ischemic stroke. Methods PatientsThis study was a single-center, prospective, observational study. The patients in this study were consecutively recruited from the Cerebrovascular Center of Chonnam National University Hospital between April 2012 and May 2...

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“…51,52 Furthermore, measurements of platelet reactivity vary over time in a significant proportion of patients. 53 Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy. In contrast, monitoring the effect of clopidogrel therapy by CYP2C19 genotyping (as discussed in the following sections) does not vary over time.…”

Section: Casementioning

confidence: 99%

How I use laboratory monitoring of antiplatelet therapy

Michelson

Bhatt

2017

Blood

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Antiplatelet therapy is of proven benefit in coronary artery disease and a number of other clinical settings. This article reviews platelet function, molecular targets of antiplatelet agents, and clinical indications for antiplatelet therapy before focusing on a frequent question to hematologists about the 2 most commonly used antiplatelet therapies: Could the patient be aspirin “resistant” or clopidogrel “resistant”? If so, should results of a platelet function test be used to guide the dose or type of antiplatelet therapy? Whether such guided therapy is of clinical benefit to patients has been a source of controversy. The present article reviews this subject in the context of 2 prototypical clinical cases. Available evidence does not support the use of laboratory tests to guide the dose of aspirin or clopidogrel in patients with so-called aspirin or clopidogrel “resistance.”

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Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel

Cited by 77 publications

References 30 publications

Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation

Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation

Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke

How I use laboratory monitoring of antiplatelet therapy

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