Prevention Of Noncardioembolic Ischemic Stroke Research Articles

Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke.

Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke. This retrospective comparative effectiveness research analyzed 1:1 propensityscorematched data from insured individuals between 2012 and 2019, using administrative claims data in Health Insurance Reviewand Assessment in Korea. Patients with diagnosis codes for ischemic stroke without cardiac disease were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding. The study analyzed 4,754 patients in the propensityscorematched population and found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 0.57-1.47) between patients receiving cilostazol and those receiving clopidogrel. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.041). This real-world study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel.

Antiplatelets in Acute Management and Prevention of Transient Ischemic Attack and Stroke

Abstract Introduction: Antiplatelet drugs (AD) reversibly or irreversibly inhibit activation and platelet aggregation and hence inhibit genesis of thrombus. Methods: In this article, we review the administration of AD in acute stroke management as well as in the primary and secondary prevention of stroke and transient ischemic attack (TIA). Conclusions: For primary stroke prevention of the first ever stroke, aspirin is advised only when a 10-year vascular risk is more than 10%, patient has a likely survival of >10 years and has a low risk for hemorrhage. For patients with acute ischemic stroke (AIS) or TIA administration of aspirin is strongly recommended within 24–48 h of symptom onset. For patients managed with IV thrombolysis, aspirin administration should be deferred for 24 h. For patients with recent minor non cardioembolic AIS and a National Institutes of Health Stroke Scale (NIHSS) score ≤3 or patients with a high-risk TIA with ABCD2 score ≥4, dual Antiplatelet therapy with aspirin and clopidogrel should be started within 12–24 h of stroke or TIA onset and definitely within a week of onset and then should be continued for a period of 21–90 days, followed by switching to a single antiplatelet therapy. The US Food and Drug Administration has given approval for Ticagrelor usage to prevent the risk of for stroke recurrence in patients with AIS with a NIHSS score of ≤5 or high-risk TIA where ticagrelor – Aspirin combination maybe prescribed for 30 days. For patients who are carriers of CYP2C19 a 90-day ticagrelor – Aspirin offers better stroke prevention. ADs in dual combination for short term and single agent in the long term remain the dominant therapy for prevention of non-cardioembolic ischemic stroke.

Possibilities of antiplatelet therapy in non-cardioembolic ischemic stroke

Most patients survive their first non-cardioembolic ischemic stroke (IS), but a significant proportion of them experience a second stroke within the first year. The main directions for the prevention of recurrent IS are antihypertensive and lipid-lowering therapy, control of glucose levels in patients with diabetes mellitus, and smoking cessation. Clinical guidelines recommend the use of antiplatelet therapy in patients with noncardioembolic IS or transient ischemic attack (TIA). The administration of antiplatelet agents to patients who have had a TIA or stroke reduces their risk of recurrent stroke by 23% and the overall risk of vascular events (myocardial infarction, stroke, and death from cardiovascular disease) by 17% (Antithrombotic Trialists' Collaboration, 2009). Acetylsalicylic acid (ASA), the combined use of clopidogrel and ASA, and the combination of ASA with sustained release dipyridamole have been shown to be effective for secondary prevention of non-cardioembolic IS. Intensive antiplatelet therapy reduces the risk of recurrent stroke, but increases the frequency of bleeding.

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

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.

The role of P2Y12 receptor in ischemic stroke of atherosclerotic origin.

Atherosclerosis is a chronic and progressive disease of the arterial walls and a leading cause of non-cardioembolic ischemic stroke. P2Y12 is a well-recognized receptor that is expressed on platelets and is a target of thienopyridine-type antiplatelet drugs. In the last few decades, P2Y12 receptor inhibitors, such as clopidogrel, have been applied for the secondary prevention of non-cardioembolic ischemic stroke. Recent clinical studies have suggested that these P2Y12 receptor inhibitors may be more effective than other antiplatelet drugs in patients with ischemic stroke/transient ischemic attack of atherosclerotic origin. Moreover, animal studies have also shown that the P2Y12 receptor may participate in atherogenesis by promoting the proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial dysfunction, and affecting inflammatory cell activities in addition to amplifying and maintaining ADP-induced platelet activation and platelet aggregation. P2Y12 receptor inhibitors may also exert neuroprotective effects after ischemic stroke. Thus, P2Y12 receptor inhibitors may be a better choice for secondary prevention in patients with atherosclerotic ischemic stroke subtypes because of their triple functions (i.e., their anti-atherosclerotic, anti-platelet aggregation, and neuroprotective activities), and the P2Y12 receptor may also serve as a noval therapeutic target for atherosclerosis. In this review, we summarize the current knowledge on the P2Y12 receptor and its key roles in atherosclerosis and ischemic stroke of atherosclerotic origin.

Antiplatelet Strategies and Outcomes in Patients with Noncardioembolic Ischemic Stroke from a Real-World Study with a Five-Year Follow-Up.

Aspirin and clopidogrel are both acceptable antiplatelet options for the secondary prevention of noncardioembolic ischemic stroke. Associations between Essen Stroke Risk Score (ESRS) and antiplatelet treatment in Chinese patients with noncardioembolic ischemic stroke were assessed. This retrospective study was taken in a tertiary care hospital located in eastern China. Patients with noncardioembolic ischemic stroke hospitalized during January 1, 2009, to December 31, 2011, were classified according to ESRS during index stroke hospitalization. Antiplatelet strategy at the time of discharge was categorized as aspirin (100mg/day) vs. clopidogrel (75mg/day). Patients received follow-up from July 1, 2014, to December 31, 2015, and the efficacy of clopidogrel and aspirin in different ESRS subgroups was assessed with respect to reducing the risk of a combined vascular event of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage. Totally, 1175 non-cardiac stroke patients were included, among which 878 patients completed follow-up surveys. Of the patients who completed the follow-up, 458 (52.2%) had an ESRS>3, and 621 (70.7%) received aspirin. Patients who received clopidogrel tended to be older, and more patients had hypertension, diabetes, and an ESRS>3 than patients who received aspirin. Over a mean follow-up of 5.2years, the rate of combined vascular events was 19.3% in the aspirin group and 16.7% in the clopidogrel group. Compared with clopidogrel-treated patients, a significant (P=0.044) reduction in combined vascular events in aspirin-treated patients was observed in patients with an ESRS≤3 (OR, odds ratio 0.5; 95% CI 0.3 to 0.9). However, a significant (P=0.002) increase in combined vascular events was observed in patients with an ESRS>3 (OR 2.2; 95% CI 1.3 to 3.8). More clopidogrel-treated patients with ESRS<3 and ESRS=3 discontinued treatment than their counterparts who took aspirin (P<0.05). Adverse drug events, such as digestive discomfort and bleeding, were similar. In conclusion, clopidogrel is suggested for patients with an ESRS>3 and aspirin for patients with an ESRS≤3 for the secondary prevention of noncardioembolic ischemic stroke in Chinese patients.

Is warfarin safe and effective for prevention of noncardioembolic ischemic stroke?

Is warfarin safe and effective for prevention of noncardioembolic ischemic stroke?

Secondary stroke prevention: misguided by guidelines?

Objectives Despite large clinical trials, there is no consensus about the best antithrombotic strategy for the secondary prevention of non-cardioembolic ischaemic stroke. This retrospective study is the fi rst to combine the results of the most important trials and to integrate data on study validity, eff ectiveness, adverse events, risk of non-compliance, and cost.Methods We searched MEDLINE, EMBASE, and the Cochrane Database (1996 to July 2011) and selected long-term secondary prevention trials with treatment with aspirin, dipyridamole, clopidogrel, aspirin plus dipyridamole, or aspirin plus clopidogrel. Subgroup analyses were included to explain diff erences in interpretations that could have led to the diff erences in guidelines.Results Two trials showed a small but signifi cant reduction with aspirin plus dipyridamole compared to aspirin (ARR 1.5%, P< 0.05 and ARR 1.0%, P< 0.05). There was no eff ect on vascular death. One trial showed a small but statistical signifi cant reduction with clopidogrel compared to aspirin (ARR 0.5%, P< 0.05). The association of clopidogrel with aspirin could not show any signifi cant benefi t compared to clopidogrel monotherapy, nor compared to aspirin monotherapy, but showed higher rates of adverse events. Signifi cantly more patients discontinued treatment with aspirin plus dipyridamole compared to aspirin monotherapy (34.5% versus 13.4% and 29.0% versus 22.2%, P< 0.001) and clopidogrel monotherapy (29.1% versus 22.6%, P< 0.001). Transposition of statistical signifi cant reductions in stroke recurrence into clinical signifi cance could not be supported.Conclusions Despite changes in international guidelines, aspirin monotherapy should retain its position as the main antiplatelet agent for secondary prevention of non-cardioembolic ischaemic stroke.

Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke

Antiplatelet therapy is more effective than anticoagulation for the prevention of noncardioembolic ischaemic stroke. The choice of antiplatelet regimen, however, remains contentious. Recent controversies regarding aspirin resistance and the optimal dosing of aspirin, as well as recognition of the variable bioactivation of clopidogrel, have added further confusion to the debate. The American Heart Association (AHA) and American Stroke Association (ASA) recently released their third joint guideline in the past 5 years on secondary stroke prevention. The European Stroke Organisation has published three guidelines on this issue since 2000. These frequent updates have been necessary because of rapidly accumulating data from clinical trials. Careful consideration of the sometimes confusing trial results reveals that the 2011 AHA-ASA guidelines are correct in no longer specifying a 'preferred' antiplatelet regimen from among the choices recently studied. This recommendation does not, however, mean that all antiplatelet regimens should be considered equal. This Review discusses the various antiplatelet regimens, and the trials that led to the rapid evolution of the guidelines for secondary prevention of ischaemic stroke.

Use of Cilostazol for Secondary Stroke Prevention: An Old Dog with New Tricks?

To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke. PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed. Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included. Antiplatelet therapy plays a vital role in the multifaceted approach to secondary stroke prevention. Current American Heart Association/American Stroke Association clinical guidelines for secondary stroke prevention support the use of aspirin, clopidogrel, and combination aspirin/extended-release dipyridamole. The antiplatelet, antithrombotic, and vasodilatory effects of cilostazol make it a potential alternative agent for atherosclerotic stroke prevention. Recent literature has demonstrated superior efficacy of cilostazol 100 mg twice daily for secondary stroke prevention compared to placebo and aspirin. Three clinical trials were reviewed (1 placebo-controlled, 2 aspirin-controlled), all of which were conducted in Japan or China. Cilostazol reduced the primary outcome of recurrence of stroke, with significantly fewer major bleeding events when compared to aspirin. Available literature suggests that cilostazol may be safer and more effective than aspirin in the secondary prevention of stroke in Asian patients. Further large-scale studies in more heterogeneous study populations are warranted to determine whether cilostazol is a viable therapeutic option for patients with a history of non-cardioembolic ischemic stroke.

New Insights in Antiplatelet Therapy for Patients With Ischemic Stroke

Acute treatment and long-term secondary prevention of noncardioembolic ischemic stroke and transient ischemic attack (TIA) include initiation of antiplatelet therapy. Antiplatelet agents currently used in the treatment of ischemic stroke and TIA are aspirin, clopidogrel, and dipyridamole. The safety and efficacy of antiplatelet therapy in patients with ischemic stroke, including a discussion of recent trial data and its influence on treatment guidelines, are presented. A brief discussion of the use of antiplatelet therapy in preventing stroke and embolism in patients with atrial fibrillation is also presented. For secondary prevention of ischemic events in patients with a history of stroke, clinical trials have shown the addition of dipyridamole to aspirin to be more effective than aspirin alone. The therapies are also similar from a standpoint of bleeding. The combination of aspirin and clopidogrel was not shown to be more efficacious and caused more bleeding than aspirin alone when evaluated for secondary prevention. However, dual antiplatelet therapy with aspirin and clopidogrel may have some benefit in the acute stroke setting or in the prevention of thrombotic events in patients with atrial fibrillation who cannot or will not take warfarin. Antiplatelet therapy is an important component of acute and long-term treatment of ischemic stroke and TIA. Ongoing clinical trials may help to refine what treatment regimens are best suited for acute and long-term therapy.

What’s new in stroke? The top 10 studies of 2009–2011. Part I

Five important studies from 2009-2011 that influence the clinical management of stroke and threatened stroke are summarized. Pooled analysis of individual patient data from 8 randomized trials testing intravenous tissue plasminogen activator confirmed important benefits for patients treated 3 to 4.5 hours after stroke onset, but treatment after 4.5 hours was associated with a higher mortality. Blood pressure lowering with candesartan in the first few days after stroke was of no benefit and was possibly harmful (SCAST trial). Thigh-length graduated compression stockings did not reduce venous thromboembolism after acute stroke and were associated with skin complications (CLOTS Trial 1). Long-term follow-up showed that endovascular coiling was as good as neurosurgical clipping for patients with small, ruptured intracranial aneurysms (ISAT trial). Percutaneous closure of a patent foramen ovale offered no apparent benefit to young patients with cryptogenic ischemic stroke based on the first randomized trial testing this intervention, but the number of stroke events was insufficient to draw definitive conclusions (CLOSURE I trial).

ORAL ANTIPLATELET THERAPY IN STROKE PREVENTION. MINIREVIEW

Antiplatelet therapy plays a crucial role in the primary and secondary prevention of noncardioembolic ischemic stroke / transient ischemic attacks (IS/TIA). Several antiplatelet agents are available. This review deals with the characteristics of particular antiplatelet agents as well as choice of antiplatelet treatment in various situations, based on the evidence and international recommendations. PubMed and Stroke Trials Registry on-line databases and the European Stroke Organisation Guidelines for Management of IS/TIA 2008 and update of the recommendations of the American Heart Association / American Stroke Association Council 2008 on Stroke were used. Acetylsalicylic acid (ASA) is the only antiplatelet drug used in primary prevention, mainly to reduce the risk of myocardial infarction (MI), but also in women aged 45 years or more and in some patients with non-valvular atrial fibrillation to reduce risk of IS/TIA. In the secondary prevention of noncardioembolic IS/TIA, ASA in combination with long release dipyridamole (DIP) and clopidogrel (CLOP) alone are considered first choice therapies. The choice of the particular antiplatelet agent should be individualized according to the patient risk factor profiles and treatment tolerance. ASA alone or triflusal can be used alternatively in patients who cannot be treated with either ASA+DIP or CLOP. The use of indobufen should be considered only in patients in need of temporary interruption of the antiplatelet therapy. Ticlopidine (TIC) should not be newly introduced into the treatment. Currently, insufficient data are available on the use of cilostazol in IS/TIA prevention.

A Critical Review of Aspirin in the Secondary Prevention of Noncardioembolic Ischaemic Stroke

Both secondary prevention (such as lifestyle modifications, pharmacotherapy or surgery) and an understanding of the influence of risk factors (including the different aetiologic mechanisms of cerebral ischaemia) play a pivotal role in reducing the burden of recurrent stroke. Regarding the types of preventative treatments available, variations exist across all clinical studies, including differences in target populations (including the type of cerebral ischaemia), risk factors, length of follow-up, drop-out rates and outcomes, which makes translating the results of clinical trials to individual patients difficult. However, with such limitations in mind, this critical albeit nonsystematic review, which compared aspirin with other antiplatelets and in combination with other drugs, showed that the benefit from aspirin treatment is consistently shown in ischaemic stroke, while harms are limited. Furthermore, no definite superiority is apparent across different antiplatelet therapies. Dual antiplatelet regimens may expose to a slight but measurable higher risk of haemorrhagic complications, perhaps in selective groups of patients (i.e. those with severe small-vessel disease or in selective racial groups). Based on our analysis, the indication of aspirin as the first-line choice, also recommended by several acknowledged international or national guidelines, may be confirmed. However, the complex nature of patients at risk of recurrent ischaemic stroke necessitates a comprehensive approach, which should be driven by the primary care physician, whose role is central to successful actions for secondary stroke prevention.

Secondary Stroke Prevention, and the Role of Antiplatelet Therapies

This review considers treatments of proved efficacy in secondary stroke prevention, with an emphasis on antiplatelet therapy. Most strokes could be prevented, if readily available lifestyle and risk factor modifications could be applied to everyone. In secondary stroke prevention, the same lifestyle and risk factor modifications are also important, along with anticoagulation for patients with cardiac sources of embolus, carotid procedures for patients with significant internal carotid artery stenosis, and antiplatelet therapy. For patients with noncardioembolic ischemic strokes, FDA-approved antiplatelet agents are recommended and preferred over anticoagulants. ASA, clopidogrel, and ASA + ER-DP are recognized as accepted first-line options for secondary prevention of noncardioembolic ischemic stroke. Combined antiplatelet therapy with ASA + clopidogrel has not been shown to carry benefit greater than risk in stroke or TIA patients. Aspirin and extended release dipyridamole appeared to carry a greater benefit over aspirin alone in individual studies, leading to a recommendation of this agent in the AHA guidelines, but the recently completed PRoFESS trial showed no difference in efficacy between clopidogrel and aspirin with extended release dipyridamole, and clopidogrel had better tolerability and reduced bleeding risk.

Systems approach to standardization of care in the secondary prevention of noncardioembolic ischemic stroke

A systems approach to stroke care is a multidisciplinary team strategy with the goal of reducing stroke risk. This strategy may start with community-based primary prevention education. For individuals who experience stroke, the inpatient component of a stroke system is designed to integrate evidence-based acute treatment and secondary prevention strategies. A key component to stroke systems care is the use of standardized, evidence-based treatment protocols. During the acute (or subacute) phase of care, the team must be prepared to prevent stroke progression, prevent complications of stroke, manage comorbidities, and reduce the risk of secondary stroke. Hospitalists may take a leadership role both in establishing stroke systems protocols at their institutions and in providing inpatient care for stroke patients. The objective of this article is to review the components of inpatient stroke systems, with a focus on care of patients with noncardioembolic ischemic stroke. Methods to minimize common barriers to establishing stroke systems programs are also presented. Journal of Hospital Medicine 2008;3(4 Suppl):S29–S35. © 2008 Society of Hospital Medicine.

Antiplatelet Therapy for Secondary Prevention of Noncardioembolic Ischemic Stroke

For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).

Adverse Effects and Drug Interactions of Antithrombotic Agents Used in Prevention of Ischaemic Stroke

Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.