Clopidogrel resistance is common in patients undergoing vascular and coronary interventions

Vascular ◽  
2022 ◽  
pp. 170853812110593
Author(s):  
Adam M Berenson ◽  
Thomas N Hawken ◽  
Daniel G Fort ◽  
Samuel R Money ◽  
Stephen R Ramee ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Thrombotic Event ◽  
Detectable Effect ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Coronary Interventions ◽  
Endovascular Interventions ◽  
Initial Cohort ◽  
Coronary Procedure ◽  
Clopidogrel Therapy

Objectives “Clopidogrel resistance,” also defined as heightened platelet reactivity (HPR) while on clopidogrel therapy, may lead to a sub-optimal antiplatelet effect and a potential thrombotic event. There is limited literature addressing the prevalence of HPR in a large cohort of patients receiving either coronary or endovascular interventions. Methods In a large integrated healthcare system, patients with a P2Y12 reaction units (PRU) test were identified. HPR was defined as a PRU ≥ 200 during clopidogrel therapy. Vascular and coronary interventions were identified utilizing CPT codes, HPR prevalence was calculated, and Fischer’s exact test was used to determine significance. Results From an initial cohort of 2,405,957 patients (October 2014 to January 2020), we identified 3301 patients with PRU tests administered. Of these, 1789 tests had a PRU ≥ 200 (HPR overall prevalence, 54%). We then identified 1195 patients who underwent either an endovascular or coronary procedure and had a PRU measurement. This corresponded to 935 coronary and 260 endovascular interventions. In the coronary cohort, the HPR prevalence was 54% (503/935). In the vascular cohort, the HPR prevalence was 53% (137/260); there was no difference between cohorts in HPR prevalence ( p = 0.78). Conclusion “Clopidogrel resistance” or HPR was found to be present in nearly half of patients with cardiovascular disease undergoing intervention. Our data suggest HPR is more common in the cardiovascular patient population than previously appreciated. Evaluating patients for HPR is both inexpensive ($25) and rapid (< 10 min). Future randomized studies are warranted to determine whether HPR has a clinically detectable effect on revascularization outcomes.

scholarly journals Clopidogrel Resistance in Lower Extremity Arterial Endovascular Interventions

2019 ◽  
Vol 24 (38) ◽  
pp. 4554-4557
Author(s):  
Kyle M. Markel ◽  
Efthymios D. Avgerinos
Keyword(s):  
Lower Extremity ◽  
Platelet Reactivity ◽  
Large Population ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Loss Of Function ◽  
Clopidogrel Resistance ◽  
Endovascular Interventions ◽  
Prospective Trials ◽  
One Year

Antiplatelet pharmacotherapy for endovascular interventions has been widely adopted, with clopidogrel being one of the most common agents prescribed. A fraction of patients is resistant to clopidogrel resulting in decreased platelet inhibition despite adequate use. This finding is often termed high on-treatment platelet reactivity (HPR) and may lead to decreased patency in lower extremity arterial endovascular interventions. Current literature on HPR with lower extremity arterial endovascular interventions is limited to only a few studies. Resistance to clopidogrel is largely a result of CYP2C19 enzyme loss of function alleles. Several tests are available to measure clopidogrel resistance but light transmittance aggregometry remains the gold standard, yet direct genetic testing may be more reliable. One-year patency rates following lower extremity arterial endovascular interventions in patients with clopidogrel resistance (HPR) range between 35%-83% whereas those with the proper response to clopidogrel range between 73%-100%. Patients with decreased CYP2C19 activity show a significant decrease in one-year patency of endovascular femoropopliteal interventions (35% vs. 73%; p=0.006). Among patients tested for platelet function after in-stent thrombosis, up to 53% are resistant to clopidogrel. Lack of robust data limits our ability to predict patency in lower extremity arterial interventions for patients with HPR, but there is little doubt that longer patency seems to favor non-HPR patients. Large population, prospective trials are needed to guide our practice.

Epigenetic interaction of miRNA-26a and P2Y12 gene DNA methylation on platelet reactivity under clopidogrel and their impact to the coronary flow after primary PCI in STEMI

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Syam ◽  
R Sukmawan ◽  
S Dharma ◽  
G Alaztha ◽  
A Giyantini ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Coronary Flow ◽  
Platelet Reactivity ◽  
Reactivity Index ◽  
Funding Source ◽  
Primary Pci ◽  
Epigenetic Factors ◽  
Clopidogrel Resistance ◽  
High Platelet Reactivity ◽  
Clopidogrel Therapy

Abstract Background Epigenetic factors such as miRNA-26A and P2Y12 DNA methylation play role in pathophysiology of cardiovascular disease. Clopidogrel-resistance is associated with worse cardiovascular outcome. The interactions between the expression of platelet miRNA-26a and P2Y12 DNA methylation to clopidogrel resistance and post procedural TIMI flow in STEMI patients undergoing primary PCI is unclear. Purpose To define interaction of epigenetic factors micro-RNA (miRNA)-26a expression and P2Y12 gene DNA methylation to the platelet reactivity under clopidogrel therapy, and their impact on the coronary flow after Primary PCI in patients with STEMI. Methods We studied STEMI patients who underwent primary PCI, receiving 600 mg loading dose of clopidogrel. Platelet reactivity assessed by VerifyNow P2Y12. Realtime PCR was performed to measure the expression of platelet miR-26a and DNA methylation of P2Y12 gene. Postprocedural epicardial coronary flow was assessed semi quantitatively. Results There were 100 patients were recruited. Among them, 59% have high miRNA-26a platelet expression, 60% had no methylation in their P2Y12 gene, and 27% had high platelet reactivity index under clopidogrel therapy. There was association between high miR-26a expression and reduced platelet inhibition under clopidogrel (OR 4.2, p&lt;0.01), but not with DNA methylation of P2Y12 gene. High platelet reactivity index under clopidogrel therapy was associated with suboptimal coronary flow after primary PCI in STEMI patients (OR 3.3, p&lt;0.05). Conclusions High miRNA-26a platelet expression, but not DNA methylation of P2Y12 gene, in patients with acute STEMI have significant association with high platelet reactivity under clopidogrel therapy. Furthermore, high platelet reactivity under clopidogrel is associated with suboptimal coronary flow in STEMI patients undergoing primary PCI. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Harapan Kita Honor Research Grant

scholarly journals The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

2020 ◽  
Vol 21 (17) ◽  
pp. 6408
Author(s):  
Adam Wiśniewski ◽  
Karolina Filipska
Keyword(s):  
Ischemic Stroke ◽  
Platelet Function ◽  
Negative Impact ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Vascular Events ◽  
Clopidogrel Resistance ◽  
Clinical Databases ◽  
Clopidogrel Therapy

Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.

scholarly journals Clopidogrel Resistance: Current Issues

2016 ◽  
Vol 6 (1) ◽  
pp. 38-46
Author(s):  
NS Neki
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Clinical Problem ◽  
Coronary Intervention ◽  
Platelet Activity ◽  
Clopidogrel Resistance ◽  
Underlying Mechanisms

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

Abstract TP227: Outcomes of a Regionalized Stroke Care System

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Denisse Sequeira ◽  
Christian Martin-Gill ◽  
Gregory Lowry ◽  
Marcus Robinson ◽  
Hinnah Siddiqui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Stroke Care ◽  
Discharge Diagnosis ◽  
Hospital Data ◽  
Exact Test ◽  
Endovascular Interventions ◽  
Good Functional Outcome ◽  
Suspected Stroke ◽  
Iv Tpa

Introduction: Strokes are one of the leading causes of death and disability. Time-sensitive therapies are available including IV-TPA and endovascular therapies which require rapid and effective triage. Endovascular therapies are available at comprehensive stroke centers (CSC). We evaluated if there was any improvement in outcomes for patients who are transported directly to a CSC. Hypothesis: Patients that receive acute interventions for stroke have improved outcomes when transferred directly to CSC as compared to transport to a PSC and then transferred to a interventional facility. Methods: A retrospective cohort study of 5,188 patients transported from January 2012 to December 2013 with an EMS provider impression of suspected stroke via both air and ground transport. Of these, data was complete for 1,196 patients with a confirmed discharge diagnosis of ischemic stroke. Pre-hospital data was abstracted from EMS charts. Ischemic strokes were identified by final hospital discharge diagnosis and good functional status was defined as a modified Rankin scale <3 at discharge. Categorical outcomes were tested using Fishers Exact Test and Ordinal outcomes using the Mann Whitney Test. Results: For those with complete data mortality was 10% (CI 8.3-11.7) in this cohort with good functional outcomes in 37% (CI 34.3-39.7) of patients. IV- TPA was administered to 293 (24%) and endovascular interventions were performed in 167 (14%). There were 739 (63%) inter-facility transfers and 442 (37%) received directly from the scene. Transport to the CSC occurred by air in 798 (67%) cases as compared to 398 (33%) by ground. Mortality and good functional outcome did not differ between patients transferred and those taken directly to the CSC. Among patients receiving either TPA or endovascular therapy, direct transport to the CSC is associated with good functional outcome (Fisher’s exact= 0.041) but not with mortality. Conclusions: Among patients with a diagnosis of ischemic stroke presenting to a CSC, there is no difference in mortality and good functional outcome as a function of transfer from the scene or transfer from another facility. However, among those who received tPA or endovascular intervention good functional outcome was associated with direct presentation to the CSC.

scholarly journals 2529

2017 ◽  
Vol 1 (S1) ◽  
pp. 67-67
Author(s):  
Dagmar Fredy Hernandez Suarez ◽  
Kyle Melin ◽  
Angel Lopez-Candales ◽  
Jorge Duconge
Keyword(s):  
Platelet Function ◽  
Clinical Characteristics ◽  
Platelet Reactivity ◽  
Artery Aneurysm ◽  
Multivariable Logistic Regression Analysis ◽  
Cross Sectional ◽  
Group I ◽  
Clopidogrel Therapy ◽  
Study Population ◽  
Artery Disease

OBJECTIVES/SPECIFIC AIMS: To determine the association between clinical characteristics and platelet reactivity in Hispanic patients on clopidogrel therapy. METHODS/STUDY POPULATION: A cross-sectional pilot study was performed in 58 Puerto Rican patients diagnosed with any type of vascular disease and actively receiving a maintenance dose of clopidogrel for at least 7 days. The study population was divided into 2 groups: Group I with non-high on-treatment platelet reactivity (TPR); Group II with high TPR. To determine the platelet function, P2Y12 reaction units (PRU) were obtained by VerifyNow® P2Y12 assay (Accumetrics, USA). RESULTS/ANTICIPATED RESULTS: We studied a heterogeneous cohort of patients with coronary artery disease (57%), peripheral artery disease (30%), carotid artery stenosis (7%), cerebral artery aneurysm (3%), and stroke (3%) on clopidogrel therapy for secondary prevention of thromboembolic events. The mean TPR was 205±49 PRU (range: 61–304), with a prevalence of 28% patients with high TPR (PRU≥230). No significant clinical differences were found between the non-high TPR and high-TPR groups (p>0.05). However, multivariable logistic regression analysis showed that both diabetes mellitus (OR=7.5; CI: 1.01–51.9) and proton-pump inhibitors (OR=13.6; CI: 1.3–142.0) were independently correlated with high TPR (p<0.05) after adjusting for other clinical variables. DISCUSSION/SIGNIFICANCE OF IMPACT: These results provide new insight into the importance of clinical characteristics on platelet reactivity in this Caribbean population. Further studies are warranted to determine whether important clopidogrel pharmacogenes are related with platelet function in Hispanics, as well as the role of TPR in guiding antiplatelet therapy and predicting future adverse cardiovascular events in this population.

Effect of bodyweight on VerifyNow Aspirin platelet function test: a retrospective review

2020 ◽  
pp. neurintsurg-2020-016842
Author(s):  
Melissa Sandler ◽  
Cuong Hoang ◽  
Hannah Y Mak ◽  
Michael R Levitt
Keyword(s):  
Stent Thrombosis ◽  
Retrospective Review ◽  
Platelet Reactivity ◽  
Thrombotic Event ◽  
Optimal Dose ◽  
Platelet Inhibition ◽  
Platelet Function Test ◽  
Assay Result ◽  
The Mean ◽  
The Impact

BackgroundAntiplatelet therapy is used to prevent stent thrombosis in intracranial stents, but the optimal dose of aspirin is unknown. This study sought to determine whether the degree of platelet inhibition with aspirin is affected by bodyweight as observed through a platelet reactivity assay.MethodsThis is a retrospective review of patients who underwent neurovascular stent placement and had a VerifyNow Aspirin assay result. The primary outcome was the correlation between the VerifyNow Aspirin result, bodyweight, and the initial dose of aspirin. Secondary outcomes included the impact of the VerifyNow P2Y12 result and of weight on the incidence of bleeding or a thrombotic event.ResultsOf the 142 included patients, 62.7% weighed ≥70 kg and 88.7% were initiated on aspirin 300–325 mg daily. 83.8% achieved a therapeutic VerifyNow Aspirin result. There was minimal correlation between the VerifyNow Aspirin result, bodyweight, and aspirin dose (R2=0.02). Between patients who weighed <70 kg versus ≥70 kg, there was no difference in the mean aspirin reaction units (ARU) (449 vs 435, p=0.32) or in the incidence of bleeding (28% vs 17.1%, p=0.14) or a thrombotic event (4% vs 5.3%, p=0.59). No patient experienced stent thrombosis and eight patients experienced in-stent stenosis. In a multivariate analysis, only the VerifyNow P2Y12 result predicted the development of either bleeding or a thrombotic event (p<0.01).ConclusionsBodyweight did not influence the likelihood of obtaining a therapeutic VerifyNow Aspirin result. The clinical utility of obtaining VerifyNow Aspirin assays for this patient population is unknown.

Platelet Reactivity in Patients on Aspirin and Clopidogrel Therapy Measured by a New Bedside Whole-Blood Assay

2019 ◽  
Vol 73 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Amin Polzin ◽  
Carolin Helten ◽  
Lisa Dannenberg ◽  
Philipp Mourikis ◽  
David Naguib ◽  
...  
Keyword(s):  
Whole Blood ◽  
Platelet Reactivity ◽  
Whole Blood Assay ◽  
Blood Assay ◽  
Clopidogrel Therapy

scholarly journals Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor

2006 ◽  
Vol 52 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Boris T Ivandic ◽  
Philipp Schlick ◽  
Peter Staritz ◽  
Kerstin Kurz ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Whole Blood ◽  
Adenosine Monophosphate ◽  
Blood Platelet ◽  
P2y12 Receptor ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Impedance Aggregometry ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 μmol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 μmol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) Ω. The mean − 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance ≤5 Ω and &gt;5 Ω, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann–Whitney U-test) was given to responders (median, 450 mg) than nonresponders (median, 300 mg). Age and cardiovascular diagnosis showed no significant associations. Conclusions: Impedance aggregometry using 5 μmol/L ADP is a useful tool for studying clopidogrel responsiveness. MeSAMP allows characterization of responsiveness “on treatment” and may be useful for optimizing clopidogrel dosing.

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