scholarly journals Advances in Our Understanding of “Resistance” to Antiplatelet Agents for Prevention of Ischemic Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Philip B. Gorelick ◽  
Muhammad U. Farooq
Keyword(s):  
Ischemic Stroke ◽  
Clinical Practice ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Patient Characteristics ◽  
Therapy Resistance ◽  
Test Methods ◽  
Platelet Function Test

We review the role of aspirin and clopidogrel for prevention of ischemic stroke and explore the concept of antiplatelet therapy resistance both from a laboratory and clinical perspective and genetic polymorphisms that might influence platelet reactivity with clopidogrel administration. Debates have raged over the years about the application of platelet function tests in clinical practice. We conclude that platelet function testing is not indicated in routine clinical practice. This recommendation is supported by clinical guideline statements, a lack of a global platelet function measure, and limitations of current platelet function test methods as applied in practice. We discuss a recently hypothesized hierarchy of patient characteristics in relation to which patients are most likely to benefit from platelet function studies based on acuity (i.e., risk) of cardiovascular disease. A focus of antiplatelet therapy administration should include emphasis on compliance/adherence and in the example of aspirin, use of well-absorbed forms of aspirin and avoidance of drugs that may interact with aspirin to inhibit its mechanism of action (e.g., certain nonsteroidal anti-inflammatory drugs).

scholarly journals Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 59
Author(s):  
Adam Wiśniewski
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Negative Impact ◽  
Platelet Reactivity ◽  
Antiplatelet Agent ◽  
Biological Response ◽  
Antiplatelet Agents ◽  
Platelet Inhibition ◽  
High Risk Group

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.

The impact of renal function on platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention with stenting

2014 ◽  
Vol 112 (12) ◽  
pp. 1174-1181 ◽  
Author(s):  
Nicoline Breet ◽  
Corine de Jong ◽  
Willem Jan Bos ◽  
Jochem van Werkum ◽  
Heleen Bouman ◽  
...  
Keyword(s):  
Renal Function ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Light Transmittance ◽  
Clinical Trial Registration ◽  
Platelet Function Test ◽  
Increased Risk ◽  
Function Test ◽  
The Impact

SummaryPatients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease. Previous studies have suggested that patients with CKD have less therapeutic benefit of antiplatelet therapy. However, the relation between renal function and platelet reactivity is still under debate. On-treatment platelet reactivity was determined in parallel by ADP- and AA-induced light transmittance aggregometry (LTA) and the VerifyNow® System (P2Y12 and Aspirin) in 988 patients on dual antiplatelet therapy, undergoing elective coronary stenting. Patients were divided into two groups according to the presence or absence of moderate/severe CKD (GFR<60 ml/min/1.73 m2). Furthermore, the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and stroke at one-year was evaluated. Patients with CKD (n=180) had significantly higher platelet reactivity, regardless of the platelet function test used. Patients with CKD more frequently had high on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) regardless of the platelet function test used. After adjustment for potential confounders, this was no longer significant. The event-rate was the highest in patients with both high on-treatment platelet reactivity (HPR) and CKD compared to those with neither high on-treatment platelet reactivity nor CKD. In conclusion, the magnitude of platelet reactivity as well as the incidence of HPR was higher in patients with CKD. However, since the incidence of HPR was similar after adjustment, a higher rate of co-morbidities in patients with CKD might be the major cause for this observation rather than CKD itself. CKD-patients with HCPR were at the highest risk of long-term cardiovascular events.Clinical Trial Registration: www.clinicaltrials.gov: NCT00352014.

Individualised Antiplatelet Therapy – Is There a Role for Platelet Function Testing in Routine Clinical Practice?

2010 ◽  
Vol 5 (1) ◽  
pp. 96 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  
Keyword(s):  
Clinical Practice ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Coronary Intervention ◽  
Platelet Function Testing ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Function Testing

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.

scholarly journals Impact of Diabetes on Platelet Function in Acute Ischemic Stroke Patients Taking Dual Antiplatelet Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinping Guo ◽  
Yi Zhang ◽  
Jing Zhao ◽  
Lingshan Wu ◽  
Zhiyuan Yu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Significant Risk ◽  
Maximum Amplitude ◽  
Stroke Patients ◽  
Clot Strength

Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT).Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis.Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P &lt; 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03–2.07, P &lt; 0.05).Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.

Individualised Antiplatelet Therapy – Is There a Role for Platelet Function Testing in Routine Clinical Practice?

2010 ◽  
Vol 6 (1) ◽  
pp. 41 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  
Keyword(s):  
Clinical Practice ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Coronary Intervention ◽  
Platelet Function Testing ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Function Testing

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.

scholarly journals Correlation between PlateletWorks® and PFA-100® for Measuring Platelet Function before Urgent Surgery in Patients with Chronic Antiplatelet Therapy

2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Rafael Anaya ◽  
Mireia Rodriguez ◽  
José María Gil ◽  
Noelia Vilalta ◽  
Angela Merchan-Galvis ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Point Of Care ◽  
Antiplatelet Agents ◽  
Kappa Coefficient ◽  
Function Evaluation ◽  
Cohen’S Kappa ◽  
Platelet Function Test ◽  
Cohen's Kappa ◽  
Cohen’S Kappa Coefficient

Hemostasis is crucial for reducing bleeding during surgical procedures. The points-of-care based on the platelet function test could be useful to minimize the complications related to chronic antiplatelet therapy during surgery. The present study is aimed at comparing two point-of-care platelet function devices—Platelet Function Analyzer PFA-100® (Siemens Canada, Mississauga, ON, Canada) and Plateletworks®(Helena Laboratories, Beaumont, TX, USA). Our objective is to evaluate if they provide comparable and useful information to manage anti-aggregate patients before surgery. We included patients with a femoral fracture receiving chronic antiplatelet therapy and a median age of 89 years (range from 70 to 98). A platelet function evaluation was performed on all patients before surgery using both devices—Plateletworks® and PFA-100®. The correlation between Plateletworks® and PFA-100® was performed using Cohen’s Kappa coefficient. Twenty consecutive patients participated in the trial; 16 patients were under treatment with 75 mg/day of clopidogrel, three with >300 mg/day of acetylsalicylic acid (ASA), and only one was in treatment with both antiplatelet agents. Cohen’s Kappa coefficient was 0.327 comparing PFA-100®-ADP (adenosine diphosphate) and Plateletworks® and, 0.200 comparing PFA-100®-EPI (epinephrine) and Plateletworks®. In conclusion, we found a weak concordance comparing PFA-100® and Plateletworks®. This could partially be due to the advanced age of the included patients. However, given the limited sample size, more studies are necessary to confirm these results.

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 How I use laboratory monitoring of antiplatelet therapy

Blood ◽  
2017 ◽  
Vol 130 (6) ◽  
pp. 713-721 ◽  
Author(s):  
Alan D. Michelson ◽  
Deepak L. Bhatt
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Molecular Targets ◽  
Antiplatelet Agents ◽  
Clinical Settings ◽  
Platelet Function Test ◽  
Function Test ◽  
Artery Disease ◽  
Proven Benefit ◽  
Guided Therapy

Abstract 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.”

Monitoring of antiplatelet therapy

2011 ◽  
Vol 31 (01) ◽  
pp. 41-51 ◽  
Author(s):  
H. Seidel ◽  
M. M. Rahman ◽  
R. E. Scharf
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
High Sensitivity ◽  
Antiplatelet Agents ◽  
Daily Practice ◽  
Adenosine Diphosphate ◽  
Poor Responders ◽  
Platelet Aggregometry

SummaryScreening of platelet function can be performed by point-of-care testing followed by platelet aggregometry in response to agonists such as collagen, adenosine diphosphate, epinephrine, and arachidonic acid. Despite in use for decades, this technique is not well standardized. Monitoring of antiplatelet therapy is increasingly applied in patients at high risk for re-thrombosis or bleeding. To assess pharmacological inhibition of platelet function, agonist-induced platelet aggregation, thromboxane B2 (TxB2) and vasodilator-stimulated protein phosphorylation (VASP) are being measured. While serum TxB2 levels of < 2 ng/ml reflect aspirin-induced inhibition of cyclo-oxygenase-1 activity with high sensitivity, VASP exhibits a wide variability upon treatment with clopidogrel or prasugrel. Multiple studies reveal an association between high residual platelet reactivity and adverse cardiovascular events in patients on antiplatelet therapy. However, despite the plethora of platelet function assays currently under investigation, their use in daily practice cannot be recommended. This is due to several reasons: (i) there is no consensus on the method and a respective cut-off value associated with clinical adverse outcome, and (ii) data demonstrating any benefit of tailored antiplatelet therapy and its monitoring (based on assessment of platelet functions) are still limited. Thus, appropriate identification of ‘resistant’ or ‘poor responders’ to antiplatelet agents remains challenging in clinical practice.

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