InfoMedSearch - Search Services Report
November, 2005
Stroke: Treatment

Arterial occlusive lesions recanalize more frequently in women than in men after intravenous tissue plasminogen activator administration for acute stroke. (Stroke. 2005) "CONCLUSIONS: In our cohort, vascular occlusive lesions were more likely to recanalize in women than men in response to IV tPA."

Arterial occlusion revealed by CT angiography predicts NIH stroke score and acute outcomes after IV tPA treatment. (AJNR Am J Neuroradiol. 2005) "CONCLUSION: Among patients treated with tPA, those with patent vasculature or occult distal occlusion on CTA before treatment have lower NIHSS, better chances of early improvement and early independence with fewer hemorrhages."

Clinical importance of microbleeds in patients receiving IV thrombolysis. (Neurology. 2005) "BACKGROUND: Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA). … CONCLUSIONS: The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset."

Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review. (Glia. 2005) "Ischemic stroke is a sudden loss of circulation to a portion of the brain that results in a loss of neurologic function. Many ischemic strokes are embolic. They result from a thrombus traveling into the central circulation and occluding a blood vessel. Treatment of ischemic stroke with recombinant tissue plasminogen activator (tPA) can improve patient outcomes. However, tPA must be used during a specific time window after the stroke onset to be effective and it risks converting an ischemic stroke into a hemorrhagic one."

Hourly blood pressure monitoring after intravenous tissue plasminogen activator for ischemic stroke: does everyone need it? (Stroke. 2004) "Background and Purpose— Blood pressure (BP) control is considered essential in patients treated with tissue plasminogen activator (tPA) for ischemic stroke, and it is recommended that BP be monitored every 15 minutes to 1 hour for 24 hours in these patients. … Conclusions— In patients receiving tPA for stroke, absence of hypertension at presentation does not preclude subsequent increase in blood pressure. However, if blood pressure is not elevated during the first 6 hours, subsequent hypertension over the next 18 hours is unlikely."

MRI screening before standard tissue plasminogen activator therapy is feasible and safe. (Stroke. 2005) "CONCLUSIONS: These data demonstrate that MRI screening before tPA therapy is feasible and not associated with unacceptable times to treatment or outcomes."

Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy. (JAMA. 2004) "CONTEXT: Data are limited regarding the risks and benefits of thrombolytic therapy for acute ischemic stroke outside of clinical trials. OBJECTIVE: To investigate predictors of in-hospital mortality in patients with ischemic stroke treated with intravenous tissue plasminogen activator (tPA) within a pooled analysis of large German stroke registers. … CONCLUSION: In patients with ischemic stroke who are treated with tPA, disturbances of consciousness and increasing age are associated with increased in-hospital mortality."

Safety and feasibility of a lower dose intravenous TPA therapy for ischemic stroke beyond the first three hours. (Cerebrovasc Dis. 2005) "BACKGROUND: The most common reason that patients do not receive intravenous tissue plasminogen activator (TPA) is the inability to meet the strict 3-hour treatment window. The risk/benefit ratio is more unfavorable beyond this time, but some patients might still benefit. We designed a pilot study with the hypothesis that lower dose TPA might be safe in selected patients treated beyond 3 h. … CONCLUSIONS: Lower dose i.v. TPA in patients presenting beyond 3 h carries a risk of intracerebral hemorrhage. However, recanalization with dramatic recovery can still occur."

The impact of imbalances in baseline stroke severity on outcome in the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study. (Ann Emerg Med. 2005) "STUDY OBJECTIVE: The National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator (rtPA) Stroke Study demonstrated a clinically meaningful and statistically significant benefit of tissue plasminogen activator (tPA). Adjusting for the baseline National Institutes of Health (NIH) Stroke Scale, the benefit of tPA remained. However, other authors suggest that an imbalance in baseline stroke severity between the tPA and placebo groups confounded the results. … CONCLUSION: These are descriptive post hoc subgroup analyses. Using cut points defined in previous critiques of the NINDS trials, these analyses give results consistent with previous NINDS Study Group reports. Baseline NIH Stroke Scale imbalance does not account for the better outcome of rtPA-treated patients."

The neurotoxicity of tissue plasminogen activator? (J Cereb Blood Flow Metab. 2004) "Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. … If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain."

[Thrombolysis in stroke: inappropriate consideration of the 'window period' as the time available] (Rev Neurol. 2005) "AIMS: The earlier r-TPA is administered in ischaemic strokes, the more effective it is. The aim of this study is to analyse the delay times in health care afforded in a consecutive series of cases that had received treatment, with a view to shortening them. … The mean time of delay until arrival, arrival-CAT, and CAT-treatment were slightly under 1 hour each, and onset-treatment delay was 165 minutes, which is very close to the limit of the therapeutic window period. … CONCLUSIONS: Findings indicate that in our hospital, as in other centres in the initial phases of implementation, the therapeutic time window for intravenous thrombolysis in ischaemic stroke tends to run out. It must be highlighted that the resolve of the physician who indicates the treatment exerts a decisive effect on the delay."

Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data. (Stroke. 2003) "BACKGROUND AND PURPOSE: Concerns persist regarding the safety of tissue plasminogen activator (tPA) therapy for acute ischemic stroke. Numerous case series of clinical experience with tPA have been published that provide additional data on the safety of thrombolytic therapy. … CONCLUSIONS: Postapproval data support the safety of intravenous thrombolytic therapy with tPA for acute ischemic stroke, especially when established treatment guidelines are followed."



Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. (Am J Cardiol. 2005) " … low-dose ASA was associated with the lowest risk, and moderate doses caused a relatively high hemorrhagic event rate, especially with regard to minor, gastrointestinal, and total bleeding, and stroke. These findings should be considered when using combination antiplatelets, anticoagulant therapy, or both, with ASA, especially with the daily dose of >100 mg."

Anti platelet therapy and the vascular tree. (Heart. 2005) " … although low to medium dose aspirin (32.5 - 75 mg daily) is well tolerated in the majority of patients, the principle adverse effects are gastro-intestinal bleeding and haemorrhagic stroke.[14-16] A meta-analysis of 16 placebo controlled trials of aspirin for cardiac and other indications found that aspirin increased the absolute risk of cerebral haemorrhage by 12 events per 30,000 person-years of follow up. Thus, the possible value of aspirin in reducing thrombosis may be weighed against the risk of bleeding, with the greatest value being in those at highest cardiovascular risk."

Application of U.S. guidelines in other countries: aspirin for the primary prevention of cardiovascular events in Japan. (Am J Med. 2004) "PURPOSE: Clinical guidelines developed in the United States are used frequently in other countries without assessment of their appropriateness in non-U.S. populations. We explored the relevance of recent U.S. guidelines for the use of aspirin for the primary prevention of cardiovascular events in the Japanese population. … RESULTS: The estimated incidence of coronary heart disease in middle-aged men in Japan is lower than in the United States (1.57 vs. 6.0 per 1000 person-years), while that of hemorrhagic stroke is higher (1.14 vs. 0.37 per 1000 person-years). Because of higher baseline rates of hemorrhagic diseases, the expected reduction in cardiovascular events with aspirin use would be offset by a greater increase in hemorrhagic complications for women and most men in Japan, except for those with both hypertension and diabetes. … CONCLUSION: The thresholds of antiplatelet therapy for Asian populations should be two to five times higher than those for the U.S. population because of higher risks of hemorrhagic complications. The assumptions and implications of U.S. guidelines should be evaluated before use in other countries."

Aspirin for Stroke Prevention Taken in the Evening? (letter to the editor - Stroke 2004)) ”For prevention patients usually take aspirin in the morning. The treatment regimen is 1 tablet (100 mg) per day to be swallowed without chewing at least 30 minutes before breakfast. … It is obvious that highest plasma level of the drug occurs after the morning peak-incidence of the thromboembolic event, suggesting lower prophylactic effect of aspirin. Furthermore, this treatment regimen has its highest protective effect during the day, when, synergistically, normal physical activity exerts a protective action on thromboembolic processes. However, this method of daily aspirin administration has its lowest protective value against cardiovascular events during the night and early morning, when the lack of physical activity further augment the cascade of hemorheological events favoring platelet aggregation and subsequent ischemia. In contrast, highest plasma level of aspirin taken late evening (10:00 PM) would be reached prior to the peak-incidence of thromboembolic disorders. We are confident that this time shift in the administration of aspirin would fit better in the circadian scheme of the occurrence of stroke, thus resulting in a significantly more effective prevention. To prove the viability of this concept we propose to set up international, randomized, multicenter studies."

Aspirin resistance in stroke: 2004. (J Neurol Sci. 2005) "Aspirin is a well-established medication in the treatment of atherothrombotic vascular disease. However, despite aspirin treatment a substantial number of patients experience recurring ischaemic episodes. Aspirin resistance denotes those situations when it is unable to protect individuals from thrombotic complications, or when it fails to produce an anticipated effect in laboratory tests of platelet function. There are various laboratory techniques with which to evaluate the effectiveness of aspirin and other antiplatelet drugs. It has been estimated that in 5-60% of patients, aspirin does not achieve adequate efficacy in various measures of platelet activity. Some studies have revealed that vascular patients shown by laboratory tests to be aspirin-resistant are at an increased risk of major vascular events."

Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. (Stroke. 2004) "CONCLUSIONS: 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."

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients (BMJ 2002) "Objective: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. … Conclusions: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed. … Antiplatelet therapy can be started promptly during acute presumed ischaemic stroke and continued long term. … Daily aspirin doses of 75-150 mg seem to be as effective as higher doses for long term treatments (and clopidrogel is an appropriate alternative for patients with a contraindication to aspirin). … These results reinforce the value of ensuring that antiplatelet therapy with 75-150 mg aspirin daily (or some other effective antiplatelet regimen) is considered routinely for all such patients at high or intermediate risk of occlusive vascular events (more than about 2% a year), irrespective of whether they have already had a major vascular event. An unanswered question, however, is whether it is possible to identify particular groups of apparently healthy people who may be at increased risk of myocardial infarction or stroke and for whom the benefits of daily aspirin outweigh the hazards. This is currently being investigated in an analysis of primary prevention trials. For most healthy individuals, however, for whom the risk of a vascular event is likely to be substantially less than 1% a year, daily aspirin may well be inappropriate."

Effects of different aspirin formulations on platelet aggregation times and on plasma salicylate concentrations. (Thromb Res. 2005) "BACKGROUND: Early aspirin treatment is widely used to inhibit platelet activity and to reduce morbidity and mortality in patients presenting with an acute myocardial infarction or a stroke. A number of different aspirin formulations have been used for this purpose; however, a comparison of their effectiveness in inhibiting early platelet aggregation has not been determined. … CONCLUSION: The results indicate that soluble and chewed aspirin inhibit platelet aggregation in a shorter period of time than does whole aspirin. The results suggest that chewing baby aspirin or taking soluble buffered aspirin may be the preferred route of administration for early platelet inhibition."

Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged > or =70. (BMJ. 2005) "OBJECTIVE: To investigate the routine use of low dose aspirin in people aged > or = 70 without overt cardiovascular disease. … CONCLUSION: Epidemiological modelling suggests that any benefits of low dose aspirin on risk of cardiovascular disease in people aged > or = 70 are offset by adverse events. These findings are tempered by wide confidence intervals, indicating that the overall outcome could be beneficial or adverse."

[Epidemiology of digestive complications associated with use of low-dose aspirin] (Gastroenterol Clin Biol. 2004) "Low-dose aspirin (< 330 mg/d) is recommended for the prevention of myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. …"

Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke. (J Neurol. 2005) "CONCLUSION : As found in the literature on nonadherence in general, age of >/= 65 years and a higher dose of aspirin (300 mg versus 30 mg) were independently associated with non-adherence with aspirin treatment that was prescribed for secondary prevention after cerebral ischaemia of arterial origin. Older patients may require extra encouragement to continue antithrombotic treatment. Lower doses of aspirin may improve treatment adherence."

What is the role of dipyridamole in long-term secondary prevention after an ischemic stroke or transient ischemic attack? (CMAJ. 2005) "Randomized trials comparing the beneficial effects and hazards of different ASA [acetyl salicylic acid - aspirin] doses have shown that daily doses of 75– 150 mg are as effective as higher doses and are associated with fewer adverse effects. … ASA exerts its antiplatelet effect by irreversibly inhibiting the enzyme cyclo-oxygenase. This causes decreased production of the platelet agonist thromboxane A2. … Dipyridamole is a pyrimidopyridine derivative with antiplatelet and vasodilator properties. Its mechanism of action on platelets remains a subject of controversy."


Warfarin prevention

Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. (N Engl J Med. 2005) "BACKGROUND: Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial. … CONCLUSIONS: Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis."

Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. (J Am Coll Cardiol. 2005) "CONCLUSIONS: This study confirms the under-use of warfarin, but also adds to published reports in several regards. It showed that risk stratification, the guidepost for treatment in international guidelines, had little effect on warfarin use, and that age >80 years and AF classification (permanent/persistent) are factors that influence warfarin use."

Low-dose warfarin in atrial fibrillation leads to more thromboembolic events without reducing major bleeding when compared to adjusted-dose--a meta-analysis. (Thromb Haemost. 2004) "The use of warfarin with a range INR of 2.0-3.0 is recommended in prevention of stroke for nonvalvular atrial fibrillation (AF) patients, in particular those older than 75 years. The risk of bleeding that is associated with this range of INR has led to evaluate lower ranges (low-dose or fixed minidose) in terms of risks and benefits. A meta-analysis of all randomized controlled trials evaluating 'low-intensity' 'minidose' or 'low-dose anticoagulant' treatment for prevention of thromboembolic events in AF was conducted by two independent reviewers. … Our meta-analysis showed that adjusted-dose compared with low-dose or minidose warfarin therapy (INR < or =1.6) was more effective to prevent ischemic thromboembolic events in patients with atrial fibrillation."

Warfarin for atrial fibrillation: the end of an era? (Lancet Neurol. 2004) " … [use of warfarin] … These barriers have included the need for monitoring the degree of anticoagulation with blood tests to measure the international normalised ratio, frequent dose adjustments to maintain this ratio within quite a narrow therapeutic range, and the risk of bleeding should the upper limits of this range be exceeded. … "


Combination Drug Treatments and Additional Information

Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. (Cochrane Database Syst Rev. 2004) "BACKGROUND: People with nonrheumatic atrial fibrillation (NRAF) who have had a transient ischemic attack (TIA) or minor ischemic stroke are at risk of recurrent stroke. Both warfarin and aspirin have been shown to reduce the recurrence of vascular events. OBJECTIVES: The objective of this review was to compare the effect of anticoagulants with antiplatelet agents, for secondary prevention, in people with NRAF and previous cerebral ischemia. … The combined results show that anticoagulants were significantly more effective than antiplatelet therapy both for all vascular events … and for recurrent stroke … Major extracranial bleeding complications occurred more often in patients on anticoagulants … but the absolute difference was small … Warfarin did not cause a significant increase of intracranial bleeds. REVIEWERS' CONCLUSIONS: The evidence from two trials suggests that anticoagulant therapy is superior to antiplatelet therapy for the prevention of stroke in people with NRAF and recent non-disabling stroke or TIA. The risk of extracranial bleeding was higher with anticoagulant therapy than with antiplatelet therapy."

Anticoagulation and platelet antiaggregation therapy in stroke prevention. (Curr Opin Neurol. 2005) "RECENT FINDINGS: Strong data have emerged to support anticoagulation with warfarin for stroke associated with inferred embolism in a setting of atrial fibrillation. No clear advantage for warfarin over aspirin exists for ischemic stroke in a setting of intracranial atheroma, patent cardiac foramen ovale, or elevated levels of antiphospholipid antibody. Among antiplatelet agents, aspirin and clopidogrel have a similar recurrent stroke risk. Combination therapies with aspirin and warfarin show no additional benefits with regard to stroke prevention and carry higher risks of hemorrhage. Treatment with aspirin combined with specially formulated long-acting dipyridamole carries a lower risk of stroke than aspirin alone and does not increase the risk of hemorrhage significantly. The combination of aspirin and clopidogrel does not reduce the risk of stroke over clopidogrel alone and carries a greater risk of bleeding than clopidogrel alone. SUMMARY: Choice of antithrombotic therapy depends on the etiology of the stroke. Oral anticoagulation treatment is the preferred choice for inferred cardioembolism in the setting of atrial fibrillation, while the varying rates of hemorrhage with oral anticoagulants continue to favor antiplatelet therapy in other settings of inferred etiology. Combinations of antithrombotic therapy vary in their lowering of stroke rate, and some raise the risk of hemorrhage."

Anticoagulation for atrial fibrillation in the elderly. (Am J Geriatr Cardiol. 2005) "Atrial fibrillation is a risk factor for stroke, particularly among elderly patients. Multiple trials have established that antithrombotic therapy decreases stroke risk. Aspirin is associated with a relative risk reduction of about 21% and adjusted-dose warfarin (international normalized ratio 2.0-3.0) is associated with a relative risk reduction of about 68%. Warfarin is more effective than aspirin but is used less often than indicated because of hemorrhagic risk and the inconvenience of coagulation monitoring."

Antiplatelet therapy and anticoagulation in patients with hypertension. (Am Fam Physician. 2005) "Clinical Question: Should we prescribe antiplatelet agents or anticoagulants for all patients with hypertension? Evidence-Based Answer: Antiplatelet agents should not be used in patients with hypertension and no previous history of heart attack or stroke. However, these agents are recommended for use in hypertensive patients who already have vascular disease. Anticoagulants should not be used for prevention of vascular events, alone or in combination with acetylsalicylic acid (ASA), in patients with elevated blood pressure. Currently, there is not enough evidence to recommend the use of glycoprotein IIb/IIIa inhibitors, ticlopidine, or clopidogrel for primary prevention of vascular events. … Practice Pointers: This review shows that aspirin should be used for prophylaxis only in patients with hypertension and a history of stroke, transient ischemic attack, myocardial infarction (MI), angina, or peripheral vascular disease. An appropriate choice and dosage of antiplatelet agent for secondary prevention would be75 or 81 mg of enteric-coated ASA daily."

Antithrombotic therapy practices in US hospitals in an era of practice guidelines. (Arch Intern Med. 2005) "CONCLUSIONS: A significant percentage of hospitalized patients do not receive adequate antithrombotic therapy for the primary and secondary prevention of thromboembolic disease."

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke (Chest. 2004) "Atherosclerosis of the arteries, large and small, that supply the brain most commonly causes ischemic stroke. Atherosclerosis of the proximal aorta is also a source of atherogenic brain emboli. Large-artery atherosclerotic infarction occurs when there is an impediment to normal perfusion, usually caused by a severe arterial stenosis or occlusion due to atherosclerosis and coexisting thrombosis or artery-to-artery embolism. Microatheroma, lipohyalinosis, and other occlusive diseases of the small penetrating brain arteries are the most frequent causes of small, subcortical "lacunar" infarcts. Approximately 20% of ischemic strokes are due to cardiogenic embolism, most commonly from atrial fibrillation. … Overall, approximately 30% of ischemic strokes remain cryptogenic despite a reasonably thorough evaluation. Cerebral angiography done within a few hours of cryptogenic stroke often reveals occlusions of intracranial arteries. Most of these occlusions resolve within a few days, suggesting transient embolic or thrombotic obstruction. Thus, the specific pathogenesis of stroke in individual patients is sometimes difficult to elucidate, and determining the optimal choice of antithrombotic therapy for prevention of stroke worsening or recurrence is challenging. … Summary of Recommendations: …" (please view summary at the end of this article)

Choosing between warfarin (Coumadin) and aspirin therapy for patients with atrial fibrillation. (American Family Physician 2005 (Point-of-Care Guides)) "What is the risk of stroke in a patient with nonvalvular atrial fibrillation, and should that patient be given warfarin (Coumadin) or aspirin? … Pooled data from randomized trials show that warfarin reduces the risk of stroke from 4.5 percent to 1.4 percent per year in patients with nonvalvular atrial fibrillation and no history of stroke or transient ischemic attack (TIA). Approximately one half of these strokes are moderate, severe, or fatal.1 Warfarin increases the risk of major hemorrhage from 1.0 percent to 1.3 percent per year and increases the risk of intracranial hemorrhage from 0.1 percent to 0.3 percent per year. Therefore, at the Seventh Conference on Antithrombotic and Thrombolytic Therapy, the American College of Chest Physicians (ACCP) recommended warfarin for atrial fibrillation patients at high risk of stroke, aspirin for patients at low risk of stroke, and either drug of patients with an intermediate risk. … "

Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. (J Am Coll Cardiol. 2004) "OBJECTIVES: This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. … CONCLUSIONS: The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients."

Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. (Eur Heart J. 2004) "AIM: To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI). … CONCLUSION: A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding."

New treatment options for stroke prevention in atrial fibrillation. (Curr Treat Options Cardiovasc Med. 2005) "Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. Its most devastating consequence is thromboembolic stroke. Therapy with warfarin is indicated in most patients, as it has been shown conclusively to reduce the risk of stroke. Aspirin is an inferior alternative except in certain low-risk patients or for patients with an absolute contraindication to warfarin. Guidelines have been published for the administration of antithrombotic therapy in AF, but many patients who are candidates for anticoagulation do not receive this therapy. …"

New treatments in acute ischemic stroke. (Curr Treat Options Neurol. 2005) "Since the advent of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (tPA) for acute ischemic stroke, there has been a marked change in our management approach to patients with acute ischemic stroke. Although the major part of our focus in treating patients with stroke remains prevention of complications post-stroke and reduction of stroke recurrence, there is a paradigm shift to immediate "clot" lysis. …Other than aspirin, the only US Food and Drug Administration-approved agent for acute ischemic stroke is intravenous tPA. Some physicians treating patients with acute ischemic stroke still frequently use heparin and low-molecular-weight heparinoids, but there are no firm data to support routine use of this drug class. However, a number of new lytic agents and strategies are being pursued. Some of these treatments, such as intra-arterial chemical thrombolysis or mechanical intra-arterial thrombolysis, are available only at specialized stroke centers."

Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. (JAMA. 2004) "CONTEXT: Atherothrombosis is a pathophysiologic process that results in clinical ischemic events affecting the cerebral, coronary, and peripheral arterial circulation. Antiplatelet agents, used alone or in combination, are effective in preventing recurrent vascular events among individuals with established vascular disease. OBJECTIVE: To summarize the current state of evidence regarding oral antiplatelet treatment in patients with cerebrovascular disease, coronary artery disease (CAD), and peripheral arterial disease. … CONCLUSIONS: Aspirin, ticlopidine, clopidogrel, aspirin combined with clopidogrel, and aspirin combined with dipyridamole are effective in preventing recurrent vascular events among various subgroups of patients with vascular disease. Current clinical trial evidence favors the use of aspirin or clopidogrel as first-line agents for the majority of patients with vascular disease. Clinical trials evaluating combination antiplatelet therapies will direct future practice."

[Preventing cerebrovascular accidents during atrial fibrillation] (Presse Med. 2005) "Atrial fibrillation, the most commonly encountered arrhythmia in clinical practice, is associated with substantial morbidity and mortality. … Pooled data from trials comparing antithrombotic treatment with placebo show that warfarin reduces the risk of stroke by 62% and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin was better than aspirin in preventing strokes, with a relative risk reduction of 36%, but the risk of major hemorrhage with warfarin was twice that with aspirin. Anticoagulation treatment needs to be tailored individually for patients on the basis of age, comorbidities, and contraindications. … "

Risk factors for stroke and thromboprophylaxis in atrial fibrillation: what happens in daily clinical practice? The GEFAUR-1 study. (Ann Emerg Med. 2004) "CONCLUSION: Most patients seen in the ED with atrial fibrillation are at high risk of stroke. Despite this risk, anticoagulation is underused in this setting, mainly because of the influence of advanced age on medical decisions and the reluctance to change current antiplatelet therapy."

[Secondary prevention of stroke with antiplatelet drugs] (Med Klin (Munich). 2004) "Patients suffering from a transient ischemic attack (TIA) or ischemic stroke are at high risk of a recurrent stroke. The risk is between 10% and 15% in the 1st year after the event and highest in the immediate period following the index event. In patients without cardiac source of embolism, the risk of stroke can be reduced by acetylsalicylic acid (ASA). The relative risk reduction for recurrent vascular events (myocardial infarction, stroke, vascular death) with aspirin is 18% and the risk reduction for stroke 13%. Clopidogrel is superior to ASA in patients with high risk of recurrence due to concomitant vascular disease or multiple risk factors."

The role of warfarin and aspirin in secondary prevention of stroke. (Curr Cardiol Rep. 2004) "The use of warfarin anticoagulation in patients with atrial fibrillation and ischemic stroke has demonstrated robust reductions in risk of recurrent events, comparable with those achieved in primary prevention. Warfarin may also be recommended for patients with other high-risk cardioembolic sources of stroke. The role of warfarin in noncardioembolic ischemic stroke is more controversial. The Warfarin Aspirin Recurrent Stroke Study found no evidence of superiority of warfarin over aspirin in stroke patients overall, nor in any major stroke subtype, including those patients with patent foramen ovale. In post-hoc analyses, there was some evidence of benefit with warfarin in patients with cryptogenic stroke without hypertension. Risks of major bleeding did not differ significantly between warfarin and aspirin groups."

The significance of prestroke aspirin dosage in fatal outcome of acute stroke. (Clin Neuropharmacol. 2005) "CONCLUSION: Prestroke medium-dose aspirin treatment was associated with reduced 30-day poststroke mortality, whereas low-dose prestroke aspirin therapy was associated with increased 30-day poststroke mortality."

The value of clopidogrel versus aspirin in reducing atherothrombotic events: the CAPRIE study. (Pharmacoeconomics. 2004) " … Data from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) study have demonstrated the significantly superior clinical benefit of clopidogrel over aspirin for secondary prevention of atherothrombotic disease, with a relative risk reduction in myocardial infarction, stroke or vascular death of 8.7% … The available data thus support the use of clopidogrel as a clinically efficient and cost-effective option for secondary prevention of atherothrombotic disease, particularly in high-risk patients."

Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. (Ann Intern Med. 2005) "BACKGROUND: After the acute coronary syndrome, adding warfarin to standard aspirin therapy decreases myocardial infarction and stroke but increases major bleeding. … CONCLUSIONS: For patients with the acute coronary syndrome who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding risks."

Ximelagatran--recent comparisons with warfarin. (Expert Opin Pharmacother. 2005) "In conclusion, although the trials comparing ximelagatran with warfarin as prophylaxis for stroke in atrial fibrillation and in the treatment of venous thromboembolism show noninferiority, concerns about the hepatic safety of ximelagatran remain."


Age Factors

Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. (Ann Intern Med. 2004) "BACKGROUND: The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity. OBJECTIVE: To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage. … CONCLUSIONS: The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided."

[Atrial fibrillation and thromboprophylaxis in elderly patients] (Z Kardiol. 2005) " … All bleeding complications occurred less frequently under therapy with ximelagatran. This could be of importance for elderly patients with risk factors for bleeding or risk of falling."

Intravenous TPA for Very Old Stroke Patients. (Eur Neurol. 2005) "Background: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. … Conclusion: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality."

Optimizing the use of antithrombotic therapy for atrial fibrillation in older people: a pharmacist-led multidisciplinary intervention. (J Am Geriatr Soc. 2005) "Conclusion: A pharmacist-led multidisciplinary process was successfully developed and implemented within the hospital setting to increase overall antithrombotic use. Having addressed some of the known barriers and limitations to warfarin use, these algorithms may allow allied health workers, patients, and clinicians to work collaboratively to achieve optimal and, importantly, appropriate (i.e., safe and effective) antithrombotic use in at-risk elderly patients."

Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (> or =80 years) stroke patients. (Stroke. 2005) "BACKGROUND AND PURPOSE: Information on safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) (IV-tPA) in very old acute ischemic stroke (AIS) patients is scarce. We studied outcome and severe hemorrhagic complications in patients aged 80 and older. … CONCLUSIONS: There is no increase in severe intracerebral hemorrhage after IV-tPA in very old patients, but outcome is worse as compared with younger patients. There is no evidence to exclude ischemic stroke patients from thrombolysis based on a predefined age threshold."

People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up. (J Am Geriatr Soc. 2005) "OBJECTIVES: To determine the incidence of major hemorrhage and stroke in people aged 76 and older with atrial fibrillation on adjusted-dose warfarin who had been recently been admitted to hospital. … CONCLUSION: The rate of major hemorrhage was high in this old, frail group, but excluding fatalities, resulted in no long-term sequelae, and the stroke rate on warfarin was low, demonstrating how effective warfarin treatment is."


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Description: Stroke treatment with TPA and Aspirin. Benefits and drawbacks and what are the side-effects? How does age affect these treatments? Include Warfarin prevention. Focus on research articles.

Keywords: stroke treatment TPA aspirin benefits drawbacks side-effects age - also warfarin prevention

Included Search Dates: focus 2004 - 2005

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