Acute Ischemic Stroke Drugs

Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke

Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone

CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage

A New Approach to Antithrombotic Therapy Evaluation of Combined Therapy of Thromboxane Synthetase Inhibitor and Very Low Dose of Aspirin

The effect of a selective thromboxane (TX) synthetase inhibitor (OKY-046), alone and in combination with a very low dose of aspirin, on the platelet function was studied in healthy and diseased subjects

A very low dose of aspirin enhances the ability of OKY-046 to inhibit platelet aggregation and this combination therapy (OKY046 100 mg and a very low dose of aspirin which inhibits platelet cyclooxygenase activity approximately 50%) may be of value as a new approach to antithrombotic therapy

A Randomized Trial of Aspirin or Heparin In Hospitalized Patients With Recent Transient Ischemic Attacks
compared the efficacy of temporary anticoagulation with intravenous heparin sodium to the efficacy of aspirin in preventing cerebral infarction in hospitalized patients with recent (<7 days) transient ischemic attacks (TIAs)

No significant difference between aspirin and heparin treatment in preventing recurrent TIAs or cerebral infarction

Antiplatelet Effect of Aspirin in Patients With Cerebrovascular Disease

Aspirin is used commonly to prevent ischemic strokes and other vascular events. Although aspirin is considered safe and effective, it has limited efficacy with a relative risk reduction of 20% to 25% for ischemic stroke. We sought to determine if aspirin as currently used is having its desired antiplatelet effects

There is a significant percentage of patients taking ASA have no detectable antiplatelet effect using the PFA-100 test. This lack of effect was most common in patients taking low-dose ASA or an enteric-coated ASA preparation

Antiplatelet Therapy in Acute Cerebral Ischemia

Antiplatelet agents are a heterogenous class of drugs that have been successfully used for more than 2 decades in secondary stroke prevention. These agents include aspirin, with or without dipyridamole, and more recently, the adenosine antagonists ticlopidine and clopidogrel

Antiplatelet drugs represent a diverse group of agents that share the ability to reduce platelet activity through a variety of mechanisms. Antiplatelet agents such as aspirin may affect both NO and prostacyclin levels, their biological activities go well beyond the platelet and include effects both locally on other blood elements and within the vessel wall

Aspirin Effective in Males Threatened with Stroke

A CLINICAL TRIAL on 2 drugs which inhibit platelet function has been concluded after 5'/2 years of cooperative effort. The results indicate that male patients threatened with stroke will benefit by the daily use of the commonest and one of the oldest pharmaceutical agents aspirin. Females will not benefit and neither men nor women will benefit from the use of sulfinpyrazone

The results indicate a clear and statistically significant risk reduction (19%, P < 0.05) from aspirin. A second analysis, omitting the TIA endpoint, indicated a 31% risk reduction in stroke or death from aspirin (P < 0.05). Sulfinpyrazone did not produce a statistically significant risk reduction for either group of events, nor was there significant synergism with, nor antagonism to, aspirin therapy. A 48% risk reduction {P < 0.005) in stroke or death was found for male patients on aspirin but females did not appear to benefit.

Aspirin Inhibits p44/42 Mitogen-Activated Protein Kinase and Is Protective Against Hypoxia/Reoxygenation Neuronal Damage

Acetylsalicylic acid (ASA) is preventive against stroke and protects against focal brain ischemia in rats. We studied the mechanisms of the manner in which ASA provides neuroprotection against hypoxia/reoxygenation (H/R) injury

ASA is neuroprotective against H/R damage partially by inhibiting the ERK signaling pathway. When one considers previous reports on the neuroprotective mechanisms of ASA, the combination of multiple pharmacological activities and sites of action may explain the beneficial effects of ASA on patients with high stroke risk

Aspirin Plus Dipyridamole Versus Aspirin for Prevention of Vascular Events After Stroke or TIA

This meta-analysis systematically reviewed randomized controlled trials comparing aspirin plus dipyridamole with aspirin alone in patients with stroke and TIA to determine the efficacy of these agents in preventing recurrent cerebral and systemic vascular events

The combination of aspirin plus dipyridamole is more effective than aspirin alone in preventing stroke and other serious vascular events in patients with minor stroke and TIAs. The risk reduction was greater and statistically significant for studies using primarily extended release dipyridamole, which may reflect a true pharmacological effect or lack of statistical power in studies using immediate release dipyridamole

Aspirin Response and Failure in Cerebral Infarction

The purpose of this study was to assess the biological effect of aspirin as measured by the inhibition of platelet aggregation in patients taking aspirin for stroke prevention and in patients with acute stroke

How the inhibition of platelet aggregation relates to stroke prevention remains unclear. The ability of aspirin and the dose required to inhibit platelet aggregation may depend upon the individual. The results of the present study suggest that noncompliance is rare and that certain individuals develop a biological effect of ASA (inhibition of platelet aggregation) at a different but greater ASA dose and that others may never respond in this manner to ASA

Aspirin Use and Incident Stroke in the Cardiovascular Health Study

Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study

These analyses of the CHS cohort in which aspirin use was largely self-determined suggest that the regular use of aspirin may be associated with increased risk of stroke, both ischemic and hemorrhagic, in older women. Among men, those with recognized cardiovascular disease who used aspirin had lower rates of stroke than nonusers of aspirin, while those who were aspirin users without cardiovascular disease had slightly higher rates, but none of these findings were statistically significant

Aspirin Versus Low-Dose Low-Molecular-Weight Heparin: Antithrombotic Therapy in Pediatric Ischemic Stroke Patients

We sought to compare different antithrombotic secondary treatments (mainly medium-dose aspirin with low-dose low-molecular-weight heparin [LMWH]) in pediatric patients with a first ischemic stroke onset with regard to the risk of stroke recurrence

This multicenter follow-up study provides evidence that drugrelated side effects were rare in both treatment arms and that low-dose LMWH is not superior to medium dose aspirin or vice versa as recurrent stroke prophylaxis in white pediatric patients

Benefit of Clopidogrel Over Aspirin Is Amplified in Patients With a History of Ischemic Events
The goal of this study was to examine the influence of preexisting symptomatic atherosclerotic disease on subsequent ischemic event rates and compare the efficacy of clopidogrel versus aspirin (acetylsalicylic acid, ASA) in patients with such disease

Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) patients with a history of prior symptomatic atherosclerotic disease had a high rate of subsequent ischemic events. The absolute benefit of clopidogrel over ASA seemed to be amplified in such high-risk patients

Biological Assessment of Aspirin Efficacy on Healthy Individuals

The widespread use of aspirin requires clarification of the aspirin resistance phenomenon. Most studies on this field are focused on patients which may affect the action of aspirin

Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research

Cerebral Hemorrhagic Risk of Aspirin or Heparin Therapy With Thrombolytic Treatment in Rabbits
We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies

Aspirin antiplatelet therapy alone may increase the risk of hemorrhagic infarction, whereas heparin or tissue plasminogen activator therapy appears to be relatively safe

Combination Therapy With Low-Dose Aspirin and Ticlopidine in Cerebral Ischemia

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction

Platelet survival was prolonged and platelet lysis was reduced after treatment with aspirin plus ticlopidine despite the fact that neither measure of platelet function was significantly altered after treatment with aspirin alone or ticlopidine alone. On the other hand, hemorrhagic complications were observed more frequently among patients treated with aspirin plus ticlopidine than among those treated with aspirin alone or ticlopidine alone. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy

Combining Aspirin With Oral Anticoagulant Therapy Is This a Safe and Effective Practice in Patients With Atrial Fibrillation?

The Stroke Prevention Using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) investigators studied the risks and benefits of combining aspirin with oral anticoagulant therapy in patients with AF

The combination therapy of aspirin with either ximelagatran or warfarin did not reduce the risk of stroke, systemic embolism, or myocardial infarction, but the addition of aspirin to warfarin or ximelagatran was associated with increased risk of bleeding, which was especially obvious when aspirin and warfarin were combined. Similar to the combination of aspirin plus clopidogrel, the combination of an antiplatelet agent and an oral anticoagulant in stroke patients seems to increase the risk of intracranial hemorrhage

Comparison of Triflusal and Aspirin for Prevention of Vascular Events in Patients After Cerebral Infarction
The efficacy of the antiplatelet agent triflusal for prevention of vascular events after stroke has been reported in a pilot study. However, there is a need to confirm those results in a larger study

This study failed to show significantly superior efficacy of triflusal over aspirin in the long-term prevention of vascular events after stroke, but triflusal was associated with a significantly lower rate of hemorrhagic complications

Differences in Medical and Surgical Therapy for Stroke Prevention Between Leading Experts in North America and Western Europe

The purpose of this analysis was to provide an informative and comparative view of the current practice of leading experts in North America (NA) and Western Europe (WE), where most of the large prevention trials have been performed

This analysis shows significant differences in several areas of stroke prevention practices between leading experts from NA and WE. Aspirin was the first-choice antiplatelet agent in patients with a recent TIA or minor stroke in both groups, recommended doses varied significantly. aspirin doses of 500 mg daily are given exclusively by American participants (36%), whereas doses ,200 mg are recommended only in Europe (51%)

Effect of Aspirin and Warfarin Therapy in Stroke Patients With Valvular Strands

Valvular strands are associated with ischemic stroke. The recurrent rate of adverse events in stroke patients with valvular strands has not been defined and, importantly, there are no randomized studies to evaluate efficacy of antithrombotic therapies in these patients

While on medical therapy, valvular strands do not significantly increase recurrent adverse event rates in patients with ischemic stroke. Furthermore, the study does not provide evidence to support an advantage of warfarin or aspirin for this purpose

Effects of Clopidogrel and Aspirin in Combination Versus Aspirin Alone on Platelet Activation and Major Receptor Expression in Patients After Recent Ischemic Stroke

To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial

Treatment with clopidogrel with aspirin (C+ASA) for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial

Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation
To determine whether introduction of fixed low-dose warfarin alone or in combination with aspirin (300 mg) could normalize hemostatic markers, namely plasma fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor-1 (PAI-1, an index of fibrinolysis), fibrinogen, and von Willebrand factor (vWf, an index of endothelial dysfunction), in a manner comparable to adjusted-dose warfarin (target INR 2.0 to 3.0)

Moreover, the introduction of 300 mg aspirin plus low-dose warfarin (1 mg/d), low-dose warfarin alone (2 mg/d), or 300 mg aspirin plus low-dose warfarin (2 mg/d) did not significantly reduce any of the hemostatic markers studied (except PAI-1 levels), whereas conventional full-dose warfarin (INR 2.0 to 3.0) significantly reduced levels of fibrin D-dimer and fibrinogen

Effects of Low-to-High Doses of Aspirin on Platelet Aggregability and Metabolites of Thromboxane A2 and Prostacyclin
The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin

Different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition

Efficacy of Ticlopidine and Aspirin for Prevention of Reversible Cerebrovascular Ischemic Events

This subgroup analysis from the Ticlopidine Aspirin Stroke Study (TASS) compared ticlopidine, a new antiplatelet agent, with aspirin for the prevention of recurrent transient ischemic attacks in patients who had a recent reversible cerebrovascular event

The results in this subgroup of patients with reversible ischemic disease, as well as the overall analysis of TASS, suggest that ticlopidine is a more effective agent than aspirin for the prevention of recurrent transient ischemic attacks

Endothelial Cell Ischemic Injury: Protective Effect of Heparin or Aspirin Assessed by Scanning Electron Microscopy

The present study was undertaken to examine the effects of heparin and aspirin in doses having significant antiplatelet aggregating activity

This investigation illustrates an endothelial abnormality which appears to be influenced by two pharmacological agents considered possibly beneficial in preventing thromboembolic phenomena related to heart attacks and strokes in man

Factors Associated With Ischemic Stroke During Aspirin Therapy in Atrial Fibrillation

Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin

Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF

Increased Platelet Sensitivity to Collagen in Individuals Resistant to Low-Dose Aspirin

The purpose of this study was to assess individual differences in the pharmacological effects of acetylsalicylic acid (ASA) on bleeding time as measured by in vitro platelet aggregation and to examine the consistency of responses over time

ASA resistance may be caused by an increased sensitivity of platelets to collagen. A platelet aggregation study specific for collagen dose response may be useful for strict selection of ASA responders for low-dose ASA therapy and for identifying ASA nonresponders for high-dose ASA therapy

Indications for Early Aspirin Use in Acute Ischemic Stroke

Starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke

Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence. No strong contraindications are apparent and that hemorrhagic stroke can be excluded with reasonable probability (with or without prior CT scan)

Low-Dose Aspirin for Prevention of Stroke in Low-Risk Patients With Atrial Fibrillation

We examined the efficacy and safety of aspirin therapy in Japanese patients with nonvalvular atrial fibrillation (NVAF) in a prospective randomized multicenter trial

For prevention of stroke in patients with NVAF, aspirin at 150 to 200 mg per day does not seem to be either effective or safe

Nonaspirin Nonsteroidal Anti-inflammatory Drugs and Hemorrhagic Stroke Risk

The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear. We examined the risk of HS associated with the use of NANSAIDs in Koreans

No increased risk of HS either subarachnoid hemorrhage or intracerebral hemorrhage was found among NANSAIDs users

Platelet Aggregation in Patients With Atrial Fibrillation Taking Aspirin or Warfarin

The purpose of this study was to determine inhibition of platelet aggregation in patients on aspirin and platelet reactivity in those on warfarin in the Stroke Prevention in Atrial Fibrillation study

Aspirin at the dosage used in the SPAF study (325 mg/d) did not completely inhibit platelet aggregation in all patients. the presence of hyperaggregable platelets in warfarin-treated patients and lack of complete inhibition of platelet aggregation in aspirin-treated patients may be related to medication failure in these patients.

Previous Use of Aspirin and Baseline Stroke Severity

Some studies suggest that taking aspirin regularly at the time of the onset of stroke reduces stroke severity. Other studies suggest the converse (ie, that previous aspirin therapy is associated with greater stroke severity). We sought to examine this question among the patients enrolled in the International Stroke Trial (IST)

No evidence that previous aspirin use has any effect on the type and severity of ischemic stroke at baseline or on the outcome at 6 months

Prospective Study of Aspirin Use and Risk of Stroke in Women

In secondary prevention, aspirin reduces risk of ischemic stroke. In primary prevention of stroke, however, the role of aspirin is uncertain, especially in women

These prospective data indicate that women who take 1 to 6 aspirin per week have a reduced risk of large-artery occlusive infarction, but those who use 15 or more aspirin per week have an increased risk of subarachnoid hemorrhage. This observational study suggests benefits of aspirin for ischemic stroke with low frequency of use and hazards for hemorrhagic stroke with high frequency of use, particularly among older or hypertensive women. Thus, the effect on total stroke will depend on the dose of aspirin and the distribution of stroke subtypes and risk factors in the population

Regular Aspirin-Use Preceding the Onset of Primary Intracerebral Hemorrhage is an Independent Predictor for Death

The effect of preceding aspirin-use on outcome after ICH is poorly investigated. We investigated short-term mortality and hematoma enlargement in subjects with ICH to find the predictors for these outcomes

We observed poor short-term outcomes and increased mortality, probably attributable to rapid enlargement of hematomas, in the subjects with ICH who had been taking regularly moderate doses of aspirin (median 250 mg) immediately before the onset of the stroke

Risk of Hemorrhagic Stroke With Aspirin Use

This review provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke, as well as insights regarding patient selection to minimize the risk of this complication

Based on the rarity of hemorrhagic stroke risk, concerns about this risk should not dissuade appropriate patients from using low-dose aspirin. Choosing doses between 75 mg and 325 mg per day provides an optimal benefit to risk relationship

Risk of Intracerebral Hemorrhage in Patients With Arterial Versus Cardiac Origin of Cerebral Ischemia on Aspirin or Placebo

To determine whether this excess risk of ICH was due to the underlying disease (cerebral ischemia of arterial versus cardiac origin) or whether it depended on the antithrombotic regimen, we studied the risk of ICH in arterial versus cardiac origin of cerebral ischemia in patients who received aspirin or no antithrombotic drugs

Our findings do not confirm the previous finding of an excess risk of ICH in patients with cerebral ischemia of arterial origin. Therefore, it seems that having cerebral ischemia of arterial origin by itself is not associated with an increased risk of ICH, but only in combination with high-intensity anticoagulation

Risks and Benefits of Oral Anticoagulation Compared With Clopidogrel Plus Aspirin in Patients With Atrial Fibrillation According to Stroke Risk

Oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (CA) in preventing vascular events in patients with atrial fibrillation. However, because OAC carries important bleeding complications, risk stratification schemes have been devised to identify patients for whom the absolute benefits of OAC exceed its risks

In this clinical trial, patients with a CHADS21 had a low risk of stroke, yet still derived a modest (1% per year) but statistically significant absolute reduction in stroke with OAC and had low rates of major hemorrhage on OAC

Screening for Aspirin Responsiveness After Transient Ischemic Attack and Stroke

The availability of simple to use point-of-care (POC) platelet function testsnow potentially allows aspirin nonresponsiveness to be identified in routine clinical practice. However, there are veryfew data on whether the different tests produce consistent results. We therefore compared 2 POC tests (PFA-100 device and the Ultegra-RPFA [RPFA]) with conventional light transmission aggregometry (LTA)

The prevalence of apparent ASA nonresponsiveness was higher with both the POC tests than with LTA. However, agreement between the tests was poor and very few patients were ASA nonresponsive by all 3 tests. Aspirin nonresponsiveness is therefore highly test-specific and large prospective studies will be required to determine the prognostic value of each of the separate tests

Therapeutic Benefit Aspirin Revisited in Light of the Introduction of Clopidogrel

Whether to switch from the well-established practice of recommending aspirin for use in patients with atherothrombotic disease, both aspirin and clopidogrel are compared with respect to the primary factors that influence such decisions

Aspirin is preferred for the majority of stroke or myocardial infarction patients at risk of recurrent atherothrombotic events. Clopidogrel may, however, provide valuable therapeutic benefit over aspirin in patients with peripheral arterial disease and in stroke or myocardial infarction patients for whom aspirin treatment is contraindicated or for whom aspirin fails to achieve the desired therapeutic effect

Thienopyridines or Aspirin to Prevent Stroke and Other Serious Vascular Events in Patients at High Risk of Vascular Disease?
Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety

The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin

Ticlopidine Versus Aspirin for the Prevention of Recurrent Stroke

We therefore performed an analysis on a subgroup of patients from the Ticlopidine Aspirin Stroke Study (TASS) with a recent minor completed stroke as the qualifying ischemic event

Ticlopidine is somewhat more effective than aspirin for reducing the risk of stroke in patients with a completed minor stroke

Use of Aspirin, Epistaxis, and Untreated Hypertension as Risk Factors for Primary Intracerebral Hemorrhage in Middle-Aged and Elderly People

The incidence of primary intracerebral hemorrhage (ICH) increases exponentially with age, but the risk factors are not well known. We investigated lifestyle factors, previous diseases, and medications as risk factors for ICH in middle-aged and elderly people

Epistaxis is a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin. Other independent risk factors are untreated hypertension, previous ischemic stroke, epilepsy, and recent strenuous physical exertion. Epistaxis may be a warning sign of an increased risk for ICH in subjects using aspirin

Clopidogrel-Associated TTP
This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis.

Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly

The Risks and Safety of Clopidogrel in Pediatric Arterial Ischemic Stroke

The purpose of this study was to determine safety and tolerability of clopidogrel in children with arterial ischemic stroke (AIS). Clopidogrel is the alternative antiplatelet medication when aspirin is not tolerated or fails

Clopidogrel to be relatively well tolerated in the pediatric population. In combination with aspirin and in the presence of other risk factors, intracranial bleeding may be seen