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 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.

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.

Abstract MP02: N-Terminal Pro-B-type Natriuretic Peptide and Risk of Stroke in Those With and Without Cerebrovascular Disease: The REGARDS Cohort

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Kara Landry ◽  
Suzanne Judd ◽  
Dawn Kleindorfer ◽  
George Howard ◽  
Virginia Howard ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebrovascular Disease ◽  
Racial Differences ◽  
Natriuretic Peptide ◽  
Stroke Recurrence ◽  
Black And White ◽  
Hazard Ratios ◽  
History Of ◽  
Ischemic Attack ◽  
Prior Stroke

Background: N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a commonly used marker of cardiac function, is associated with presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke and mortality. Little data are available on the association between NT-pro-BNP levels and stroke recurrence. Objective: We studied the relationship between NT-proBNP with the risk of future ischemic stroke across a spectrum of pre-existing cerebrovascular conditions, ranging from history of stroke symptoms, to prior transient ischemic attack (TIA), to prior stroke. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans age 45 years and older in 2003-14. Among a case-cohort study sample including 1109 stroke cases and a 4311-person cohort random sample, we calculated hazard ratios of future ischemic stroke by baseline NT-proBNP stratified by presence of prior cerebrovascular conditions. Results: In the cohort sample, there were 3056 participants without any history of cerebrovascular disease, 738 with prior stroke symptoms, 196 with history of TIA and 338 with history of prior stroke. In a fully adjusted model, elevated NT-proBNP was associated with risk of stroke in participants without a pre-existing cerebrovascular condition (HR 2.32, 95% CI 1.84, 2.94), and in participants with a history of stroke symptoms (HR 1.67 95% CI 1.01, 2.78) or TIA (HR 2.66, 95% CI 1.00, 7.04), but not among those with prior stroke (HR 1.26, 95% CI 0.71, 2.21). Conclusions: These findings further support the potential for NT-proBNP testing to identify patients who are at highest risk for future stroke, although not in those with prior stroke.

scholarly journals Antiplatelet therapy in stroke prevention after non-cardioembolic transient ischemic attack

2021 ◽  
Vol 13 (5) ◽  
pp. 14-19
Author(s):  
A. V. Fonyakin ◽  
L. A. Geraskina ◽  
M. Yu. Maksimova
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Transient Ischemic Attack ◽  
Antiplatelet Agents ◽  
Basic Principles ◽  
Advantages And Disadvantages ◽  
Minor Ischemic Stroke ◽  
New Ideas ◽  
Ischemic Attack

The review shows modern concepts on the role of antiplatelet therapy in the secondary prevention of cardiovascular diseases in patients after non-cardioembolic ischemic stroke or transient ischemic attack (TIA). We present an analytical characteristic of all antiplatelet agents that have been studied in randomized controlled trials worldwide. We demonstrate the advantages and disadvantages of each agent in monotherapy and in combination. New ideas about the rationality of the use of combined antiplatelet therapy with clopidogrel and acetylsalicylic acid in the first 24 hours and no more than 90 days in patients with minor ischemic stroke or TIA are discussed. The efficacy and safety of new antiplatelet agents are analyzed. The basic principles of choosing antiplatelet agents in patients after ischemic noncardioembolic stroke/TIA are outlined.

Abstract WP424: Efficacy Of Antiplatelet Therapy For Secondary Stroke Prevention Following Lacunar Stroke: A Meta-analysis And Pooled Analysis Of Randomized Controlled Trials

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ashkan Shoamanesh ◽  
Chun Shing Kwok ◽  
Phyo K Myint ◽  
Yoon K Loke ◽  
Hannah Copley ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Lacunar Stroke ◽  
Stroke Patients

INTRODUCTION: The predominant underlying mechanism of lacunar stroke differs from that of other ischemic stroke subtypes. Accordingly, so may the ideal stroke prevention regimen. We aimed to evaluate the efficacy of different antiplatelet agents in lacunar stroke patients. Method: We searched MEDLINE, EMBASE and the Cochrane library for RCTs that evaluated antiplatelet therapy in patients with ischemic stroke. Trials which provided stroke recurrence rates in patients presenting with lacunar stroke, or where the data was obtainable from manuscript authors were included. In addition, we included the novel SPS3 trial’s antiplatelet arm data presented at the 2011 ISC. We performed pooled analysis to assess the crude frequency of recurrent stroke and a random effects meta-analysis. Results: Lacunar stroke data was available for 12 trials encompassing 35, 218 participants (mean age 65, 65% male). The pooled crude recurrent stroke rate was least for cilostazol monotherapy (6.2%), followed by ASA monotherapy (7.4%), clopidogrel monotherapy (8.6%), ASA/dipyridamole (8.6%) and greatest for ASA/clopidogrel therapy (9.1%). Rate ratios of lacunar stroke patients suggest no significant efficacy advantage for ASA [ASA vs placebo (RR 0.72, 95% CI 0.34-1.50; p=0.38)], ASA/clopidogrel [ASA/clopidogrel vs ASA (RR 0.80, 95% CI 0.62-1.03; p=0.08), ASA/clopidogrel vs clopidogrel (RR 0.95, 95% CI 0.79-1.15; p=0.63)], sarpogrelate [sarpogrelate vs ASA (RR 1.31, 95% CI 0.84-2.04; p=0.23)] and ASA/dipyridamole [ASA/dipyridamole vs ASA (RR 0.90, 95% CI 0.70-1.16; p=0.042)] for recurrent stroke. The results from Japanese trials evaluating the efficacy of cilostazol found that it is significantly better than both placebo (RR 0.51, 95% CI 0.30-0.85; p=0.01) and ASA (RR 0.70, 95% CI 0.51-0.96; p=0.03) in the secondary prevention of stroke. Conclusions: There seems to be no significant advantage among the various antiplatelet agents studied in lacunar stroke patients apart for cilostazol. However, this requires confirmation within large randomized trials outside of Japanese populations.

Abstract 13426: Percent Time With a Supratherapeutic Inr in Atrial Fibrillation Patients Using an Antiplatelet Agent is Associated With Long-term Risk of Dementia

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Thomas J Bunch ◽  
Heidi T May ◽  
Tami L Bair ◽  
Victoria Jacobs ◽  
Brian G Crandall ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antiplatelet Therapy ◽  
Antiplatelet Agent ◽  
Cerebral Injury ◽  
Percent Time ◽  
Dementia Risk ◽  
Dementia Incidence ◽  
History Of ◽  
Intermountain Healthcare

Background: Patients with atrial fibrillation (AF) are at higher risk of developing all forms of dementia. The mechanisms behind the association of AF and dementia are unknown. One possibility is that exposure to chronic microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. We hypothesize that AF patients receiving antiplatelet therapy will display higher rates of dementia if coupled with a higher percentage of time exposed to over-anticoagulation. Methods: Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) with no history of dementia or stroke/TIA and receiving antiplatelet therapy were included. The primary outcome was the presence of dementia defined by neurology determined ICD-9 codes. Percent time with an INR above 3.0 was determined. Multivariable Cox hazard regression was utilized to determine dementia incidence by percentage categories of supratherapeutic INR. Results: A total of 1031 patients were studied. Of these, the categories of the mean percent time with an INR >3.0 were 25% (n=240). Patients with a higher percent of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure (Cr>2.0), a higher percent of CHADS 3-6 scores, and a prior bleed. Dementia was diagnosed in 2.7% of patients with supratherapeutic INR levels 25%, p=0.05. Those with a supratherapeutic INR >25% of the time were at an increased dementia risk throughout follow-up. After multivariate adjustment, those with levels >25% had significantly higher rates of dementia compared to those with levels <10% (HR 2.40, p=0.04). Discussion: In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over anticoagulation increases risk of dementia. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism that underlies the association of AF and dementia.

Abstract 15701: Relationship Between Cardiac Biomarkers and Major Adverse Cardiovascular Events in DECLARE-TIMI 58

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Thomas A Zelniker ◽  
David A Morrow ◽  
ofri Mosenzon ◽  
Erica Goodrich ◽  
Petr Jarolim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Controlled Trial ◽  
Cardiac Biomarkers ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Vascular Disease ◽  
Cox Models ◽  
Increased Risk ◽  
History Of ◽  
The Difference ◽  
The Relationship

Introduction: Biomarkers of hemodynamic stress and myocardial injury are associated with the risk of CV death & heart failure in patients with atherosclerotic vascular disease (ASCVD). Here we explore the association between cardiac biomarkers and ASCVD outcomes in patients with type 2 diabetes (T2DM). Methods: This was a nested biomarker study in DECLARETIMI 58, a randomized, blinded, placebo-controlled trial of dapagliflozin in T2DM and either multiple risk factors (MRF, ~60%) or established ASCVD (~40%). The relationship between baseline NT-proBNP and hsTnT levels (TIMI Biomarker Laboratory, n=14,565) and the composite of myocardial infarction, ischemic stroke, and CV death (MACE), was modeled within the placebo arm using Cox models adjusted for age, sex, race, smoking, baseline eGFR, BMI, T2DM duration, insulin use, history of CAD, MI, ischemic stroke, PAD, HF, dyslipidemia & hypertension. Interaction testing was applied to assess the effect of dapagliflozin according to baseline biomarker value. Results: NT-proBNP and hsTnT were significantly associated with MACE (Adjusted hazard ratio (aHR) per 1-SD in log-transformed biomarker, NT-proBNP: aHR 1.62; hsTnT aHR 1.59). The magnitude of the relationship was similar in patients with ASCVD (NT-proBNP aHR 1.60; hsTnT aHR 1.62) and MRF (NT-proBNP aHR 1.62; hsTnT: aHR 1.51) [Fig A] . Moreover, both biomarkers remained independently associated with MACE when combined in the multivariable model (NT-proBNP aHR 1.46, hsTnT aHR 1.39). The risk of MACE by baseline biomarker level and stratified by treatment arm is shown in Fig B. Conclusions: In patients with T2DM both with and without ASCVD, higher baseline NT-proBNP or hsTnT levels identified patients at increased risk of MACE. The difference in MACE rates between dapagliflozin and placebo tended to be more pronounced in ASCVD patients with higher baseline or NT-proBNP or hsTnT levels.

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