scholarly journals Antithrombotic Therapy in the Prevention of Stroke

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1906
Author(s):  
Shyamal Bir ◽  
Roger E. Kelley

Overview: Ischemic stroke is a leading cause of death and disability throughout the world. Antithrombotic therapy, which includes both antiplatelet and anticoagulant agents, is a primary medication of choice for the secondary prevention of stroke. However, the choices vary with the need to incorporate evolving, newer information into the clinical scenario. There is also the need to factor in co-morbid medical conditions as well as the cost ramifications for a particular patient as well as compliance with the regimen. Pertinent Updates: In the acute setting, dual antiplatelet therapy from three weeks to up to three months has become recognized as a reasonable approach for patients with either minor stroke or transient ischemic attack or those with symptoms associated with higher-grade intracranial stenosis. This approach is favored for non-cardioembolic stroke as a cardiogenic mechanism tends to be best managed with attention to the cardiac condition as well as anticoagulant therapy. Risk stratification for recurrent stroke is important in weighing potential risk versus benefits. For example, prolonged dual antiplatelet therapy, with a combination such as aspirin and clopidogrel or aspirin and ticagrelor, tends to have negation of the potential clinical benefit of stroke prevention, over time, by the enhanced bleeding risk. Anticoagulant choices are now impacted by newer agents, initially identified as novel oral anticoagulants (NOACs), which also became associated with “non-vitamin K” agents as they are no longer considered novel. Alternatively, they are now often identified as direct oral anticoagulants (DOACs). They tend to be viewed as superior or non-inferior to warfarin with the caveat that warfarin is still viewed as the agent of choice for stroke prevention in patients with mechanical heart valves. Conclusion: Based upon cumulative information from multiple clinical trials of secondary prevention of stroke, there is an increasing array of approaches in an effort to provide optimal management. Antithrombotic therapy, including in combination with anticoagulant therapy, continues to evolve with the general caveat that “one size does not fit all”. In view of this, we desire to provide an evidence-based approach for the prevention of stroke with antithrombotic agents.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ying Xian ◽  
Haolin Xu ◽  
Deepak L Bhatt ◽  
Gregg C Fonarow ◽  
Eric E Smith ◽  
...  

Introduction: Aspirin is one of the most commonly used medications for cardiovascular disease and stroke prevention. Many older patients who present with a first or recurrent stroke are already on aspirin monotherapy, yet little evidence is available to guide antithrombotic strategies for these patients. Method: Using data from the American Heart Association Get With The Guidelines-Stroke Registry, we described discharge antithrombotic treatment pattern among Medicare beneficiaries without atrial fibrillation who were discharged alive for acute ischemic stroke from 1734 hospitals in the United States between October 2012 and December 2017. Results: Of 261,634 ischemic stroke survivors, 100,016 (38.2%) were on prior aspirin monotherapy (median age 78 years; 53% women; 79.4% initial stroke and 20.6% recurrent stroke). The most common discharge antithrombotics (Figure) were 81 mg aspirin monotherapy (20.9%), 325 mg aspirin monotherapy (18.2%), clopidogrel monotherapy (17.8%), and dual antiplatelet therapy (DAPT) of 81 mg aspirin and clopidogrel (17.1%). Combined, aspirin monotherapy, clopidogrel monotherapy, and DAPT accounted for 86.8% of discharge antithrombotics. The rest of 13.2% were discharged on either aspirin/dipyridamole, warfarin or non-vitamin K antagonist oral anticoagulants with or without antiplatelet, or no antithrombotics at all. Among patients with documented stroke etiology (TOAST criteria), 81 mg aspirin monotherapy (21.2-24.0%) was the most commonly prescribed antithrombotic for secondary stroke prevention. The only exception was those with large-artery atherosclerosis, in which, 25.3% received DAPT of 81 mg aspirin and clopidogrel at discharge. Conclusion: Substantial variations exist in discharge antithrombotic therapy for secondary stroke prevention in ischemic stroke with prior aspirin failure. Future research is needed to identify best management strategies to care for this complex but common clinical scenario.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Brett L Cucchiara ◽  
Jordan Elm ◽  
J Donald Easton ◽  
Shelagh Coutts ◽  
Joshua Willey ◽  
...  

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.


Neurology ◽  
2018 ◽  
Vol 90 (6) ◽  
pp. e447-e454 ◽  
Author(s):  
Jiejie Li ◽  
Anxin Wang ◽  
Xingquan Zhao ◽  
Liping Liu ◽  
Xia Meng ◽  
...  

ObjectiveTo determine the relationship of high-sensitive C-reactive protein (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.MethodsA subgroup of 807 patients with both magnetic resonance angiography images and hsCRP measurement was analyzed. Cox proportional hazards models were used to assess the interaction of hsCRP levels with the effects of dual and single antiplatelet therapy.ResultsA total of 358 (44.4%) patients had ICAS and 449 (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There was significant interaction between hsCRP and the 2 antiplatelet therapy groups in their effects on recurrent stroke after adjustment for confounding factors in the patients with ICAS (p = 0.012), but not in those without (p = 0.256). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p = 0.006). Similar results were observed for composite vascular events. No significant difference in bleeding was found.ConclusionsPresence of both ICAS and nonelevated hsCRP levels may predict better response to dual antiplatelet therapy in reducing new stroke and composite vascular events in minor stroke or high-risk TIA patients. Further large-scale randomized and controlled clinical trials are needed to confirm this finding.


BMJ ◽  
2018 ◽  
pp. k5130 ◽  
Author(s):  
Kameshwar Prasad ◽  
Reed Siemieniuk ◽  
Qiukui Hao ◽  
Gordon Guyatt ◽  
Martin O’Donnell ◽  
...  

What is the role of dual antiplatelet therapy after high risk transient ischaemic attack or minor stroke? Specifically, does dual antiplatelet therapy with a combination of aspirin and clopidogrel lead to a greater reduction in recurrent stroke and death over the use of aspirin alone when given in the first 24 hours after a high risk transient ischaemic attack or minor ischaemic stroke? An expert panel produced a strong recommendation for initiating dual antiplatelet therapy within 24 hours of the onset of symptoms, and for continuing it for 10-21 days. Current practice is typically to use a single drug


Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Adam Wiśniewski ◽  
Joanna Sikora ◽  
Aleksandra Karczmarska-Wódzka ◽  
Przemysław Sobczak

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.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yilong Wang ◽  
Jing Jing ◽  
Yongjun Wang

Background and Purpose: TIAregistry.org project showed that TIA and minor stroke patients with multiple acute infarctions (MAIs), which represent mechanisms of embolism, are at higher risk of recurrent stroke as compared to those with none or single acute infarction (SAI). We hypothesis that patient with MAIs may be more susceptible to dual antiplatelet therapy. Methods: We compared clopidogrel plus aspirin with aspirin alone with regard to their effectiveness and safety for prevention of stroke recurrence among non-cardiac TIA and minor ischemic stroke patients with different infarction patterns (no acute infarction, SAI, or MAIs) in the imaging subgroup from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. The efficacy and safety outcome were stroke recurrence and moderate-to-severe bleeding event at 90 days respectively. Results: Overall, 1089 patients at 45 centers in CHANCE trial were included. The rate of recurrent stroke was 14.2%, 8.7%, and 2.0% in patients with MAIs, SAI and no infarction respectively at 90 days. Increased risk of stroke recurrence was observed in patients with MAIs (HR, 5.9; 95% CI, 2.3-15.2) and SAI (HR, 4.1; 95% CI, 1.6-10.7) (Figure A) as compared to those without infarction. The dual antiplatelet treatment was superior to aspirin alone for reducing the risk of recurrent stroke in patients with MAIs (HR 0.48; 95% CI, 0.25- 0.92; P = 0.03) but not in patients with SAI and without acute infarction with P=0.046 for interaction (Figure B-D). The effect of treatment assignment on bleeding did not vary among groups with different infarction patterns ( P >0.05 for all). Conclusions: Patients with MAIs had the highest risk for stroke recurrence among patients with different infarction patterns. Patients with MAIs may benefit the most clinically from dual antiplatelet therapy and dual antiplatelet therapy does not increase the risk of hemorrhage among any groups.


2019 ◽  
Vol 5 (4) ◽  
pp. 298-309 ◽  
Author(s):  
Francesca Pugliese ◽  
Punitha Arasaratnam ◽  
Marcus Moellenberg ◽  
Sourbha Dani

Abstract Aims  This review aimed to compare the efficacy and safety of short-term (≤3 months) and long-term (≥1 year) dual-antiplatelet therapy (DAPT) in secondary prevention for ischaemic stroke. Methods and results  We searched MEDLINE, EMBASE (Ovid), PubMed, Cochrane Library, ClinicalTrials.gov, and Google Advanced Search for randomized controlled trials. The population consisted of patients with recent ischaemic stroke or transient ischaemic attack. The intervention was DAPT with a combination of aspirin, clopidogrel, and dipyridamole compared to either aspirin or clopidogrel in monotherapy. The primary outcome was the rate of all recurrent stroke (ischaemic and haemorrhagic). Secondary outcomes were ischaemic stroke, all bleeding, severe bleeding, all-cause death, cardiovascular death, and myocardial infarction. Data were pooled by network metanalysis and pairwise metanalyses. Sixteen studies with 55 261 participants were included. Compared to aspirin, DAPT with aspirin clopidogrel decreased the risk of recurrent stroke [short-term odds ratio (OR) 0.67, 95% confidence interval (CI) 0.58–0.77; long-term OR 0.84, 95% CI 0.70–1.01] at the expense of increased risk of bleeding (short-term OR 1.76, 95% CI 1.26–2.46; long-term OR 2.25, 95% CI 1.97–2.57). Dual antiplatelet therapy with aspirin clopidogrel and clopidogrel in monotherapy had similar long-term risk of recurrent stroke (OR 0.98, 95% CI 0.83–1.14), but DAPT was associated with increased risk of bleeding (OR 2.77, 95% CI 2.21–3.46). Network metanalysis showed that short-term aspirin clopidogrel DAPT had the best risk-benefit profile, followed by long-term aspirin clopidogrel DAPT and clopidogrel alone. Aspirin dipyridamole DAPT was less effective. Conclusion  Short-term DAPT had better risk-benefit profile than long-term DAPT.


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