Dual Antiplatelet Therapy of Clopidogrel and Aspirin in Secondary Prevention of Ischemic Stroke: Evidence and Indications

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.

Download Full-text

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

Vascular ◽

10.1177/1708538113484022 ◽

2013 ◽

Vol 22 (3) ◽

pp. 181-187 ◽

Cited By ~ 5

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.

Download Full-text

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

Medicina ◽

10.3390/medicina57010059 ◽

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.

Download Full-text

Abstract 104: Disability After Minor Stroke and TIA in the POINT Trial

Stroke ◽

10.1161/str.51.suppl_1.104 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Brett L Cucchiara ◽

Jordan Elm ◽

J Donald Easton ◽

Shelagh Coutts ◽

Joshua Willey ◽

...

Keyword(s):

Ischemic Stroke ◽

Adverse Events ◽

Antiplatelet Therapy ◽

Primary Outcome ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Primary Outcome Measure ◽

Minor Stroke ◽

Serious Adverse Events ◽

Index Event

Background and Purpose: To assess the effect of combination antiplatelet therapy with aspirin and clopidogrel versus aspirin alone on disability following TIA or minor stroke and to identify factors associated with disability. Methods: The POINT trial randomized patients with TIA or minor stroke (NIHSS≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, MI, or vascular death. We performed a post-hoc exploratory analysis to examine the effect of treatment on overall disability (defined as mRS>1) at 90 days as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results: At 90 days, 188/1964 (9.6%) of patients enrolled with TIA and 471/2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% vs. 14.3%, OR 0.97, 95%CI 0.82-1.14, p=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% vs. 4.0%, OR 0.73, 95%CI 0.53-1.01, p=0.06), and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% vs. 7.4%, OR 0.78, 95% CI 0.62-0.99, p=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% vs. 6.0%, OR 0.74 95% CI 0.57-0.96, p=0.02). In multivariate analysis of patients enrolled with TIA, disability was significantly associated with age, subsequent ischemic stroke, serious adverse events, and major bleeding. In patients enrolled with stroke, disability was associated with female sex, hypertension, diabetes, NIHSS score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events. Conclusions: In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, dual antiplatelet therapy might reduce stroke-related disability.

Download Full-text

Guideline: Starting dual antiplatelet therapy ≤ 24 h after high-risk TIA or minor ischemic stroke is recommended

Annals of Internal Medicine ◽

10.7326/acpj201904160-038 ◽

2019 ◽

Vol 170 (8) ◽

pp. JC38

Author(s):

Ken Uchino

Keyword(s):

Ischemic Stroke ◽

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Minor Ischemic Stroke

Download Full-text

Dual Antiplatelet Therapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Events

Clinical Therapeutics ◽

10.1016/j.clinthera.2020.08.003 ◽

2020 ◽

Vol 42 (10) ◽

pp. 2084-2097

Author(s):

Paul P. Dobesh ◽

Shannon W. Finks ◽

Toby C. Trujillo

Keyword(s):

Secondary Prevention ◽

Antiplatelet Therapy ◽

Cardiovascular Events ◽

Dual Antiplatelet Therapy

Download Full-text

Dual antiplatelet therapy in the secondary prevention of atherothrombosis: Need for new therapeutic approaches

Archives of Cardiovascular Diseases ◽

10.1016/j.acvd.2010.06.007 ◽

2010 ◽

Vol 103 (10) ◽

pp. 497-501

Author(s):

Brigitte Sabatier ◽

Ludovic Trinquart ◽

Joseph Emmerich

Keyword(s):

Secondary Prevention ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Therapeutic Approaches ◽

New Therapeutic Approaches

Download Full-text

Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series

The Canadian Journal of Hospital Pharmacy ◽

10.4212/cjhp.v71i6.2849 ◽

2019 ◽

Vol 71 (6) ◽

Author(s):

Jodi R DeGrote ◽

Elizabeth M Olafson ◽

Alexander Drofa ◽

Evgueni Kouznetzov ◽

Michael Manchak ◽

...

Keyword(s):

Ischemic Stroke ◽

Acetylsalicylic Acid ◽

Cerebral Aneurysm ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Case Series ◽

Bleeding Complications ◽

Attractive Alternative ◽

Pipeline Embolization Device ◽

End Point

ABSTRACT Background: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12-receptor antagonist is often used to prevent thrombotic complications after placement of a Pipeline embolization device (PED) for cerebral aneurysm. Although clopidogrel is common in this setting, high rates of nonresponse to this drug have made ticagrelor a potentially attractive alternative. Objective: To describe safety and efficacy outcomes for ticagrelor following PED placement, including measurement of platelet function. Methods: A retrospective analysis of data was completed for patients who underwent PED placement for cerebral aneurysm at a single centre between November 2015 and March 2017, with subsequent prescription of ticagrelor and ASA as dual antiplatelet therapy. The primary end point was any ischemic stroke or death within 1 year after the procedure. Intracranial hemorrhage was a secondary end point. Additionally, measurement of and values for platelet reactivity units (PRUs) during receipt of ticagrelor and ASA were evaluated. Results: A total of 29 patients were included in this retrospective study. One patient experienced ischemic stroke 226 days after placement of the PED. In addition, 3 patients died during the 1-year follow-up period for causes unrelated to stroke or bleeding complications. No cases of intra -cranial hemorrhage were observed. Samples for measurement of P2Y12 levels were drawn at the discretion of the neurointerventionalists, and the PRU value was measured at least once for 28 (97%) of the 29 patients. The mean number of PRU measurements per patient after initiation of ticagrelor was 2.1 (standard deviation [SD] 1). Mean PRU value after initiation of ticagrelor was 65 (SD 57). Conclusions: In this case series describing the use of ticagrelor and ASA as dual antiplatelet therapy after PED placement for cerebral aneurysm, there was just one ischemic stroke, which occurred after the dual antiplatelet therapy had been discontinued. Further prospective trials are needed to describe the utility of ticagrelor use after PED placement, as well as its dosing and monitoring.RÉSUMÉContexte : Une bithérapie antiplaquettaire composée d’acide acétylsali-cylique (AAS) et d’un inhibiteur du récepteur P2Y12 est fréquemment utilisée pour prévenir les complications thrombotiques après la mise en place d’un dispositif d’embolisation Pipeline pour traiter un anévrisme cérébral. Quoique le clopidogrel soit souvent utilisé dans ce contexte, des taux élevés d’absence de réponse à ce médicament ont fait du ticagrélor une solution de rechange potentiellement intéressante. Objectif : Décrire les résultats relatifs à la sécurité et à l’efficacité du ticagrélor après la mise en place d’un dispositif d’embolisation, y compris l’analyse de la fonction plaquettaire. Méthodes : Une analyse rétrospective de données a été réalisée dans un seul centre entre novembre 2015 et mars 2017 à l’aide des dossiers médicaux de patients chez qui a été posé un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral et à qui a ensuite été prescrite une bithérapie antiplaquettaire de ticagrélor et d’AAS. Le critère d’évaluation principal était les cas d’infarctus cérébral ou de décès durant l’année suivant l’opération. Les cas d’hémorragie intracrânienne ont servi de critère d’évaluation secondaire. De plus, l’analyse a porté sur l’évaluation de la réactivité plaquettaire et sa quantification en unités de réaction au P2Y12 pendant la prise de ticagrélor et d’AAS. Résultats : Au total, 29 patients ont été admis à la présente étude rétrospective. Un patient a subi un infarctus cérébral 226 jours après la mise en place d’un dispositif d’embolisation Pipeline. De plus, 3 patients sont décédés au cours de la période de suivi d’un an en raison de causes sans lien avec des complications liées à un accident vasculaire cérébral ou à une hémorragie. Aucun cas d’hémorragie intracrânienne n’a été observé. Les échantillons destinés à la mesure des unités de réaction au P2Y12 ont été prélevés selon le jugement des neuro-intervenants et l’évaluation de la réactivité plaquettaire a été réalisée au moins une fois chez 28 (97 %) des 29 patients. Le nombre moyen de mesures des unités de réaction au P2Y12 par patient était de 2,1 (écart-type de 1). Après l’amorce d’un traitement par ticagrélor, le résultat moyen en unités de réaction au P2Y12 était de 65 (écart-type de 57).Conclusions : Dans la présente série de cas décrivant l’utilisation d’une bithérapie antiplaquettaire composée de ticagrélor et d’AAS après la mise en place d’un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral, seul un cas d’infarctus cérébral a été observé et il s’est produit après l’arrêt de la bithérapie antiplaquettaire. De plus amples études prospectives sont nécessaires pour décrire l’utilité et la posologie du ticagrélor ainsi que le suivi du traitement après la mise en place d’un dis-positif d’embolisation Pipeline.

Download Full-text