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.

scholarly journals Antiplatelet Therapy in the Secondary Prevention of Non-cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Vališ ◽  
Blanka Klímová ◽  
Michal Novotný ◽  
Roman Herzig
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
English Studies ◽  
Transient Ischemic Attacks ◽  
Severe Stroke ◽  
Neurological Outcomes ◽  
Ischemic Attack

The aim of this mini-review is to discuss the main antiplatelet agents that have been successfully used in the secondary prevention of non-cardioembolic ischemic stroke and transient ischemic attacks (TIA). The methodology is based on a literature review of available peer-reviewed English studies listed in PubMed. The findings reveal that aspirin remains a reliable antiplatelet agent in the secondary prevention of acute non-cardioembolic ischemic stroke and TIA. Nevertheless, currently, there are also other agents, i.e., ticagrelor, clopidogrel, and cilostazol, that can be applied. In addition, the results indicate that time is significant not only in severe stroke but also in non-severe stroke and TIA, which suggests that antiplatelet therapy should be applied within 24 h after the first symptoms because early treatment can lead to an improvement in neurological outcomes and reduce the chance of an early subsequent stroke.

Abstract 207: Vorapaxar in Patients with Prior Ischemic Stroke: Primary Results from the Stroke Cohort of the Multinational TRA 2°P-TIMI 50 Trial

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
David A Morrow ◽  
Mark Alberts ◽  
Jay P Mohr ◽  
Sebastian Ameriso ◽  
Marc Bonaca ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Controlled Trial ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Primary Efficacy ◽  
Background Therapy ◽  
History Of ◽  
Double Blinded ◽  
Prior Stroke

Vorapaxar is an antiplatelet agent that potently inhibits thrombin-mediated activation of the platelet protease-activated receptor (PAR)-1. Phase 2 trials of vorapaxar suggested efficacy with acceptable safety in patients with ischemic stroke. Methods: TRA 2°P–TIMI 50 was a multinational, randomized, double-blinded, placebo-controlled trial of 26449 patients with a history of atherothrombosis randomized to vorapaxar (2.5 mg daily) or matching placebo added to standard therapy, including antiplatelet agents. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 wks to 12 mo. The first efficacy endpoint was the composite of cardiovascular (CV) death, MI, or stroke. After 2 years, the Data and Safety Monitoring Board recommended discontinuation of study treatment in patients with prior stroke. Results: The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other in 18%. Background therapy included aspirin in 81%, clopidogrel in 22%, and dipyridamole in 19%. In the stroke cohort, the 3-year rate of CV death, MI, or stroke was not reduced with vorapaxar vs. placebo (13.0% vs. 11.7%, HR 1.03; 95% CI 0.85-1.25), including recurrent ischemic stroke (HR 0.99; 95% CI 0.78-1.25). There were no statistically significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke, and a borderline interaction based on co-administration of clopidogrel (Figure) The rate of intracranial hemorrhage (ICH) at 3 years was 2.5% with vorapaxar vs. 1.0% with placebo (HR 2.52; 95% CI 1.46-4.36). Conclusions: In patients with prior stroke receiving standard antiplatelet therapy, adding vorapaxar increased the risk of ICH without a reduction in the primary efficacy endpoint or ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.

scholarly journals A Combination of Aspirin and Clopidogrel Predict More Favorable Dynamics of Platelet Reactivity versus Clopidogrel Alone in the Acute Phase of Minor Stroke

Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Adam Wiśniewski ◽  
Joanna Sikora ◽  
Aleksandra Karczmarska-Wódzka ◽  
Przemysław Sobczak
Keyword(s):  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Small Vessel Disease ◽  
Platelet Reactivity ◽  
Antiplatelet Agent ◽  
Adenosine Diphosphate ◽  
Minor Stroke ◽  
Impedance Aggregometry ◽  
Over Time

Background: The combined use of clopidogrel and aspirin is recommended for the short-term (21 days) therapy of minor stroke or transient ischemic attack. Previous studies have demonstrated its efficacy and superiority over treatment with a single antiplatelet agent. However, there is insufficient support for the advantages of such therapy based on platelet function testing. We aimed to compare the effect of the concomitant use of clopidogrel and aspirin versus clopidogrel alone on the dynamics of platelet reactivity over time to determine the appropriate antiplatelet treatment strategy for minor strokes. Methods: We enrolled 74 ischemic stroke subjects, including 38 minor strokes. Platelet reactivity was assessed by impedance aggregometry (Multiplate Analyzer) 48 and 96 h after a first 75 mg dose of clopidogrel, using the acetylsalicylic acid platelet inhibition (ASPI) test and the adenosine diphosphate (ADP) test. Dual antiplatelet therapy was strictly reserved only to minor strokes, as the other strokes received clopidogrel alone in the secondary prevention. The dynamics of platelet reactivity refer to the difference between two assessments, and a decrease in values over time was considered favorable. Results: The incidence of clopidogrel non-responsiveness was 64.8%, and this was similar in the group of minor strokes and the group of more disabling strokes. We indicated diabetes mellitus as an independent predictor of high on-clopidogrel platelet reactivity (Odds ratio OR 5.69 95% Confidence Interval CI 1.13–41.26, p = 0.0386). Among minor strokes treated with dual antiplatelet therapy, in relation to clopidogrel, we reported a trend toward more favorable dynamics of platelet reactivity over time compared to the group using clopidogrel alone (p = 0.0652 vs. p = 0.3384, respectively). We identified five predictors (sex, female; small-vessel disease; no diabetes; no hyperlipidemia; and no alcohol abuse) related to a significant decrease in platelet reactivity over time with respect to clopidogrel. No significant dynamics of platelet reactivity when using aspirin were found. Conclusions: Our findings, based on the favorable dynamics of platelet reactivity over time in relation to clopidogrel, confirm the usefulness of dual antiplatelet therapy in minor strokes and support the continuation of the secondary prevention with clopidogrel alone rather than aspirin, particularly among identified beneficiaries of such a strategy.

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 Personalisation of antiplatelet therapy and secondary prevention of ischemic stroke.

2018 ◽  
Vol 96 (8) ◽  
pp. 677-687
Author(s):  
E. Yu. Kitaeva ◽  
V. V. Shprakh ◽  
K. B. Mirzaev ◽  
D. A. Sychev
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Current Approach ◽  
Antiplatelet Drugs ◽  
Laboratory Evaluation ◽  
Functional Studies ◽  
Prognostic Tests ◽  
Personalized Approach

The purpose of this systematic literature review is to highlight the current approach to the issue of “resistance” to antiplatelet drugs, presentation of a personalized approach to antiplatelet therapy in the treatment and secondary prevention of ischemic stroke, taking into account new foreign and Russian recommendations and research results. To achieve this goal, a systematic search was carried out with subsequent analysis of literary data and online resources. All reviews were indexed in PubMed, Medline, elibrary, CyberLeninka, Google Scholar databases. The article presents the main characteristics of the methods of laboratory evaluation of residual platelet reactivity used in clinical practice. It is shown that one of the rational approaches to improving the effectiveness and safety of antiplatelet therapy is to test the sensitivity ofpatients to the antiplatelet action of drugs (aggregatometry). In turn, pharmacogenetic testing makes it possible to predict the pharmacological response to the drug and is one of the promising prognostic tests that allow to assess the characteristics of individual sensitivity to the appointment of drug therapy. Particular emphasis in this review of the literature is made on a comprehensive approach, including the use ofpharmacogenetic and functional studies, the results and prospects of the results and prospects ofpharmacogenetic testing in the personalization of antiplatelet therapy of ischemic stroke in order to achieve the effectiveness of the greatest effect of antiplatelet drugs and reduce the risk of adverse reactions. This approach is important because it allows you to correct antiplatelet therapy in the treatment and secondary prevention of ischemic stroke in a timely manner, which makes it possible to develop an algorithm to achieve the effectiveness of antiplatelet therapy, choose an individual dose of the drug and the treatment regimen.

scholarly journals Review of Toyoda K, et al. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischemic stroke in Japan. Lancet Neurol. 2019 Jun;18(6):539-548

2020 ◽  
Vol 11 ◽  
pp. 53
Author(s):  
Benjamin W. Y. Lo ◽  
Satoru Miyawaki ◽  
Hitoshi Fukuda ◽  
Masaomi Koyanagi
Keyword(s):  
Randomized Controlled Trial ◽  
Ischemic Stroke ◽  
High Risk ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Controlled Trial ◽  
Antiplatelet Agent ◽  
Dual Therapy ◽  
Randomized Controlled

Background: Prior meta-analyses showed that treatment with cilostazol, with or without aspirin, significantly reduced the incidence of recurrent ischemic stroke, occurrence of hemorrhagic stroke, and frequency of other serious vascular adverse events. Methods: This review highlights the value of the randomized controlled trial (RCT) by Toyoda et al. entitled, “Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischemic stroke in Japan: a multicenter, open-label, randomized controlled trial.” Here, dual therapy consisting of cilostazol and another antiplatelet agent was used to prevent secondary ischemic stroke in high-risk Japanese patients. Results: Patients on dual therapy consisting of cilostazol/aspirin or cilostazol/clopidogrel had significantly lower frequencies of recurrent stroke. However, there were significant differences in the incidence of attendant hemorrhagic complications utilizing mono or dual therapy. Conclusion: This RCT demonstrated the safety of dual therapy, consisting of cilostazol/aspirin or cilostazol/ clopidogrel, in preventing secondary ischemic stroke in a high-risk Japanese population. Further studies are required to generalize these findings to other patient populations worldwide.

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 Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

2021 ◽  
Author(s):  
Suvro Sankha Datta ◽  
Dibyendu De ◽  
Nadeem Afroz Muslim
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P Value ◽  
Platelet Response ◽  
Percutaneous Coronary ◽  
The Individual ◽  
Platelet Functions

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine disdiphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

Evaluation on the compliance with secondary prevention and influence factors of ischemic stroke in Hainan province, China

Vascular ◽  
2013 ◽  
Vol 22 (3) ◽  
pp. 181-187 ◽  
Author(s):  
Qingjie Su ◽  
Kunxiong Yuan ◽  
Faqing Long ◽  
Zhongqin Wan ◽  
Chaoyun Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Health Education ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Influence Factors ◽  
Significant Risk ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Logistic Regression Models ◽  
Prevention Therapy

Survivors of ischemic stroke are still at a significant risk for recurrence. Numerous effective strategies for the secondary prevention of ischemic stroke have now been established; however, these guidelines are not widely known. In this retrospective, a multicenter study was conducted from January 2011 to February 2012 in 10 general hospitals, which included 1300 elderly patients who had previously been diagnosed with ischemic stroke and re-admitted to hospitals. Logistic regression models were fitted to determine the relationship between compliance with secondary prevention therapy and each variable of interest. The treatment rates of antihypertensive, antiplatelet and lipid-lowering therapy were only 56.3%, 48.9% and 19.6%, respectively. Multivariate analysis presented that cardiovascular risk factors would motivate patients with hypertension and hyperlipidemia to receive corresponding treatments. However, it is worth noting that they did not influence the use of antiplatelet therapy. In addition, high education, health education and insurance promote the use of secondary prevention in patients. In conclusion, the importance of antiplatelet therapy should not be ignored any more. Besides, health education will raise patients’ attention to ischemic stroke.

Clopidogrel pretreatment in primary percutaneous coronary intervention: Prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery

2013 ◽  
Vol 110 (07) ◽  
pp. 110-117 ◽  
Author(s):  
Javier Berdejo ◽  
Gerard Roura ◽  
Josep Gómez-Lara ◽  
Rafael Romaguera ◽  
Luis Teruel ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Primary Percutaneous Coronary Intervention ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Poor Response ◽  
Antiplatelet Agents ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Percutaneous Coronary ◽  
Infarct Related Artery

SummaryTo date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.

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