warfarin and Ischemic-Attack--Transient

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature.. Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Topics: Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Warfarin

Anticoagulant therapy increases the risk that cerebral microbleeds (CMBs) progress to intracerebral hemorrhage, but whether the therapy increases risk of CMB occurrence is unclear. We performed a systematic review and meta-analysis to investigate the potential association between anticoagulant use and CMB occurrence in stroke and stroke-free individuals.. We searched observational studies in PubMed, Ovid EMBASE, and Cochrane Library from their inception until September 2019. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) for the prevalence and incidence of CMBs in anticoagulant users relative to non-anticoagulant users.. Forty-seven studies with 25,245 participants were included. The pooled analysis showed that anticoagulant use was associated with CMB prevalence (OR 1.54, 95% CI 1.26-1.88). The association was observed in subgroups stratified by type of participants: stroke-free, OR 1.86, 95% CI 1.25-2.77; ischemic stroke/transient ischemic attack, OR 1.33, 95% CI 1.06-1.67; and intracerebral hemorrhage, OR 2.26, 95% CI 1.06-4.83. Anticoagulant use was associated with increased prevalence of strictly lobar CMBs (OR 1.68, 95% CI 1.22-2.32) but not deep/infratentorial CMBs. Warfarin was associated with increased CMB prevalence (OR 1.64, 95% CI 1.23-2.18), but novel oral anticoagulants were not. Anticoagulant users showed higher incidence of CMBs during long-term follow-up (OR 1.72, 95% CI 1.22-2.44).. Anticoagulant use is associated with higher prevalence and incidence of CMBs. This association appears to depend on location of CMBs and type of anticoagulants. More longitudinal investigations with adjustment for confounders are required to establish the causality.

Topics: Anticoagulants; Cerebral Hemorrhage; Humans; Ischemic Attack, Transient; Magnetic Resonance Imaging; Risk Factors; Stroke; Warfarin

The introduction of NOACs has put a focus on stroke prevention in atrial fibrillation (AF). The number of patients in Stockholm diagnosed with non-valvular AF increased from 41 008 in 2011 to 51 266 in 2017 and their treatment has been markedly improved. Between 2011 and 2017 total oral anticoagulant treatment increased from 51.6% (warfarin) to 77.3% (31% warfarin, 46.3% NOACs) and aspirin decreased from 31.6% to 7.2%. Treatment was especially improved among patients with CHA2DS2-VASc scores ≥2 and elderly high risk patients. We found an excellent persistence with OAC treatment (88% at 1 year and 83% at 2 years). A comparative effectiveness study showed that NOACs were at least as effective and safe as warfarin even among patients ≥80 years or with previous serious bleeds. After a gradual introduction of NOACs with many educational activities apixaban is now the first-line choice for stroke prevention in AF in Stockholm. Swedish guideline goals are fulfilled and outcomes are improved.

Topics: Aged, 80 and over; Antithrombins; Atrial Fibrillation; Dabigatran; Humans; Ischemic Attack, Transient; Observational Studies as Topic; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Sweden; Thiazoles; Warfarin

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk; Stroke; Warfarin

Anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) is of paramount importance for prevention of thromboembolic events, and recent studies favor uninterrupted vitamin K antagonists (VKAs). We aimed to compare the efficacy and safety of new oral anticoagulants (NOACs) to uninterrupted VKAs for anticoagulation in CA by performing a meta-analysis. PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov databases were searched for studies comparing NOACs with uninterrupted VKAs in patients who underwent CA for AF from January 1, 2000, to August 31, 2015. Odds ratio (OR) and Peto's OR (POR) were used to report for event rates >1% and <1%, respectively. A total of 11,686 patients with AF who underwent CA in 25 studies were included in this analysis. There was no significant difference between NOACs and uninterrupted VKAs in occurrence of stroke or transient ischemic attacks (POR 1.35, 95% CI 0.62 to 2.94) and major bleeding (POR 0.87, 95% CI 0.58 to 1.31), which were consistent in subgroup analysis of interrupted and uninterrupted NOACs. A lower risk of minor bleeding was observed with NOACs (OR 0.80, 95% CI 0.65 to 1.00), and no major differences were observed for the risk of thromboembolic events, cardiac tamponade or pericardial effusion requiring drainage, and groin hematoma. NOACs, whether interrupted preprocedure or not, were associated with equal rates of stroke or TIA and major bleeding complications and less risk of minor bleeding compared with uninterrupted VKAs in CA for AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dabigatran; Factor Xa Inhibitors; Humans; Ischemic Attack, Transient; Observational Studies as Topic; Prothrombin; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding.. We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79).. Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

Topics: Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Drug Administration Schedule; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Ischemic Attack, Transient; Odds Ratio; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

Japanese Guidelines for the Management of Stroke 2015 was published. Here, we describe several points revised from the 2009 edition about "Cerebral infarction and transient ischemic attack (TIA)". The revision points are as follows; 1. Extension of possible time window of intravenous recombinant tissue-plasminogen activator treatment (from within 3 hours to within 4.5 hours); 2. Antiplatelet therapy in acute stage (dual antiplatelet therapy (DAPT) for non-cardioembolic ischemic stroke or TIA); 3. Endovascular recanalization therapy in acute stage; 4. Antiplatelet therapy in chronic stage (Cilostazol is recommended similar to aspirin or clopidogrel); 5. Non-vitamin K antagonist oral anticoagulants (NOACs) for non-valvular atrial fibrillation (NVAF) stroke or TIA patients; 6. Management of TIA. We explain the revised points of the guideline in the text.

Topics: Acute-Phase Reaction; Anticoagulants; Cerebral Infarction; Dabigatran; Endovascular Procedures; Factor Xa Inhibitors; Humans; Ischemic Attack, Transient; Japan; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Recombinant Proteins; Recurrence; Rivaroxaban; Tissue Plasminogen Activator; Warfarin

Strokes, whether ischaemic or haemorrhagic, are the most feared complications of atrial fibrillation (AF) and its treatment. Vitamin K antagonists have been the mainstay of stroke prevention. Recently, direct oral anticoagulants have been introduced. The advantages and disadvantages of these treatment strategies have been extensively discussed. In this narrative review, we discuss dilemmas faced by primary care clinicians in the context of stroke and transient ischaemic attack (TIA) in patients with AF. We discuss the classification of stroke, the different types of stroke seen with AF, the prognosis of AF-related strokes, the early management after AF-related stroke or TIA and the therapeutic options after anticoagulant-associated intracerebral haemorrhage. Most importantly, we aim to dispel common misconceptions on the part of non-stroke specialists that can lead to suboptimal stroke prevention and management.

Topics: Anticoagulants; Atrial Fibrillation; Disease Management; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Prognosis; Stroke; Vitamin K; Warfarin

The majority of patients with nonvalvular atrial fibrillation (AF) will require anticoagulation therapy for reducing the risk of stroke, the most devastating complication of AF. Although traditionally vitamin K antagonists have been used for this purpose, they have important limitations that interfere with their use in clinical practice. Different clinical trials have shown the benefits of new oral anticoagulants over warfarin, but patients included in the ROCKET-AF trial were found to be at a higher risk of AF-related complications. Moreover, rivaroxaban has been proven to be effective and safe in patients with AF and moderate renal dysfunction as well as in those with ischemic heart disease. Rivaroxaban is taken only once daily; this may improve medication adherence and, secondarily, it provides a higher protection and reduction in the risk of stroke. This article provides an extensive review of the available evidence about rivaroxaban, with a special focus on nonvalvular AF.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Humans; Ischemic Attack, Transient; Medication Adherence; Morpholines; Renal Insufficiency; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thromboembolism; Vitamin K; Warfarin

Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).. Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.. In patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.. NOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Secondary Prevention; Stroke; Warfarin

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Vitamin K; Warfarin

To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin.. We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies.. Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139).. In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Humans; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Stroke; Vitamin K; Warfarin

To determine the strength of evidence supporting an accentuated bleeding risk when patients with CHADS(2) risk factors (chronic heart failure, hypertension, advanced age, diabetes, and prior stroke/transient ischemic attack) receive warfarin.. A systematic literature search of MEDLINE (January 1, 1950, through December 22, 2009) and Cochrane CENTRAL (through December 22, 2009) was conducted to identify studies that reported multivariate results on the association between CHADS(2) covariates and risk of bleeding in patients receiving warfarin. Each covariate was evaluated for its association with a specific type of bleeding. Individual evaluations were rated as good, fair, or poor using methods consistent with those recommended by the Agency for Healthcare Research and Quality. The strength of the associations between each CHADS(2) covariate and a specific type of bleeding was determined using Grading of Recommendations Assessment, Development and Evaluation criteria as insufficient, very low, low, moderate, or high for the entire body of evidence.. Forty-one studies were identified, reporting 127 multivariate evaluations of the association between a CHADS(2) covariate and bleeding risk. No CHADS(2) covariate had a high strength of evidence for association with any bleeding type. For the vast majority of evaluations, the strength of evidence between covariates and bleeding was low. Advanced age was the only covariate that had a moderate strength of evidence for association; this was the strongest independent positive predictor for major bleeding. Similar findings were observed regardless of whether all included studies, or only those evaluating patients with atrial fibrillation, were assessed.. The associations between CHADS(2) covariates and increased bleeding risk were weak, with the exception of age. Given the known association of the CHADS(2) score and stroke risk, the decision to prescribe warfarin should be driven more by patients' risk of stroke than by the risk of bleeding.

Topics: Aging; Anticoagulants; Atrial Fibrillation; Chronic Disease; Confounding Factors, Epidemiologic; Diabetes Complications; Heart Failure; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Observer Variation; Risk Factors; Stroke; Warfarin

A major challenge facing the physician evaluating patients with transient ischemic attack is determining which patients are at highest short-term risk of stroke. A number of stratification schemes have been recently developed incorporating easily obtainable clinical information about the individual patient. Further, emerging data suggest a role for brain and vascular imaging in risk stratification. Many aspects of acute management of transient ischemic attack, such as which patients should be hospitalized and choice of acute antithrombotic therapy, remain controversial because of a lack of evidence from controlled trials. For longer-term prevention, there is much firmer evidence from multiple large randomized trials, and these data are reviewed in this article.

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Endarterectomy, Carotid; Humans; Ischemic Attack, Transient; Magnetic Resonance Imaging; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prognosis; Risk Assessment; Stroke; Warfarin

Antiphospholipid antibodies have been associated with a clinical syndrome consisting thrombosis and recurrent, unexplained fetal loss.. The literature pertaining to stroke associated with antiphospholipid antibodies, with emphasis on stroke in young adults, was reviewed.. Antiphospholipid antibodies are an independent risk factor for stroke in young adults in five of six studies. Multiple antiphospholipid specificities or the Lupus Anticoagulant were tested in addition to anticardiolipin antibody in these studies. In the single study that found no increased risk for stroke, only anticardiolipin antibody was tested. Only one of these studies evaluated for risk of recurrent stroke in young adults with antiphospholipid antibodies and found it to be increased. No treatment trials have been conducted in young adults with antiphospholipid antibodies and stroke. In the single treatment trial comparing aspirin and low-INR producing doses of warfarin to prevent recurrent stroke, both were found to be equally effective.. Antiphospholipid antibodies, particularly Lupus Anticoagulant, is an independent risk factor for first and possibly recurrent ischemic stroke in young adults. The best therapeutic strategy for preventing antiphospholipid antibody-associated recurrent stroke is not clear.

Topics: Adolescent; Adult; Age Factors; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Humans; Ischemic Attack, Transient; Lupus Coagulation Inhibitor; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Stroke; Thrombosis; Warfarin

Antithrombotic therapy plays a central role in secondary prevention after ischemic stroke and transient ischemic attack. The choice among warfarin, aspirin, and other antiplatelet agents, however, depends on the cause of stroke and other individual patient characteristics. 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. For most patients with noncardioembolic strokes, therefore, antiplatelet therapy is the preferred option, although clinician experience still dictates practice in individual situations. Newer antiplatelet agents, and the combination of novel agents with aspirin, are also finding a role in stroke prevention as clinical trial data become available.

Topics: Anticoagulants; Aspirin; Clopidogrel; Heart Septal Defects, Atrial; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Treatment Outcome; Warfarin

Patients with stroke commonly undergo investigations to determine the underlying cause of stroke. These investigations often include ambulatory electrocardiography to detect paroxysmal atrial fibrillation. There is conflicting evidence in the literature regarding whether routine ambulatory electrocardiography should be performed in all or selected stroke patients. This paper reviews the available evidence on (1) the yield of ambulatory electrocardiography in detecting paroxysmal atrial fibrillation in patients with stroke or transient ischemic attack and (2) the effectiveness of anticoagulation in preventing recurrent stroke in patients with paroxysmal atrial fibrillation.. A MEDLINE search for primary articles was performed, and the references were reviewed manually. In addition, citations were obtained from experts. The evidence was systematically reviewed using the evidence-based methodology of the Canadian Task Force on Preventive Health Care.. Ambulatory electrocardiography can detect atrial fibrillation not found on initial electrocardiogram in between 1% and 5% of people with stroke. Ambulatory electrocardiography is generally safe. The risk of recurrent stroke in the setting of paroxysmal atrial fibrillation is uncertain, but appears to be similar to that seen with chronic atrial fibrillation (about 12% per year). Therapy with warfarin may reduce this risk by about two-thirds as compared to placebo. The annual risk of major bleeding with warfarin therapy is between 1% and 3% but rates for individual patients depend on various specific risk factors.. There is insufficient evidence to recommend for or against the use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in either selected or unselected patients with stroke (C Recommendation). There is fair evidence to recommend therapy with warfarin for patients with stroke and paroxysmal atrial fibrillation (B Recommendation).

Topics: Anticoagulants; Atrial Fibrillation; Electrocardiography, Ambulatory; Humans; Ischemic Attack, Transient; Stroke; Warfarin

Ischemic stroke is a common disorder associated with significant morbidity and mortality. Results of several pivotal clinical trials completed within the last decade have helped refine stroke prevention and treatment strategies. Endarterectomy for symptomatic carotid artery stenosis, anticoagulation in atrial fibrillation, and IV t-PA treatment of hyperacute ischemic stroke may reduce the burden of stroke. Ongoing studies are addressing newly recognized risk factors, such as aortic arch and intracranial atherosclerosis, as well as neuroprotective agents and locally delivered thrombolytics. Successful patient management requires a targeted clinical approach based on vascular localization and risk factor assessment.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atrial Fibrillation; Brain Ischemia; Endarterectomy, Carotid; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Recurrence; Risk Factors; Tissue Plasminogen Activator; Warfarin

Atrial fibrillation(AF) is a common arrhythmia that is an important independent risk factor for stroke. The overall risk of stroke in AF patients averages about 5%/y, but with wide variation depending on the presence of coexistent thromboembolic risk factors, which include increasing age, history of hypertension, previous stroke or transient ischemic attack(TIA), and diabetes. AF patients with prior stroke or TIA are at highest risk(about 12%/y). Adjusted-dose warfarin(target INR 2.0-3.0) is highly efficacious for preventing stroke in AF patients, and is safe for selected patients. Aspirin has a modest effect on reducing stroke. Warfarin is recommended for high-risk AF patients who can safely receive it. Aspirin may be indicated for those with a low stroke risk and for those who cannot receive warfarin.

Topics: Age Factors; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Diabetes Complications; Humans; Hypertension; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Thromboembolism; Warfarin

The consensus on antithrombotic prophylaxis of vascular incidents in patients with manifest atherosclerotic vasculopathy was preceded by a systematic classification of results from relevant articles according to 'evidential value': from randomized prospective trials of sufficient quality and size, via less adequate or non-randomized trials to the current opinion in the Netherlands. The principal advice was to prescribe antithrombotic prophylaxis, mostly acetylsalicylic acid, for patients with manifest atherosclerotic vasculopathy (in head, heart and (or) legs). With regard to the question what drug should be preferred for patients with intermittent claudication, no consensus could be reached for lack of adequate research. Acetylsalicylic acid is not more effective in higher than in lower doses, but in higher doses it has more side effects; therefore lower doses are preferred: 80-100 mg per day, and for neurological indications, 30 mg or more per day. Use of coumarin derivates is only to be preferred in patients with atrial fibrillation who have suffered a TIA or a non-crippling cerebral infarction, in patients with atrial fibrillation and a cardiac disorder such as large myocardial infarction or a left ventricular aneurysm, and in patients who have undergone a cardiac valve operation. Since the proportion of pros and cons of antithrombotic prophylaxis may change during a patient's life, the indication should be reconsidered periodically.

Topics: Anticoagulants; Arteriosclerosis; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Disease; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

A 35-year-old woman was admitted to our hospital with complaints of a two-year history of recurrent, daily episodes of transient ischemic attacks; the symptoms consisted of scotoma of her left eye, vertical diplopia, and paresthesia of her right arm. The presence of lupus anticoagulants and anticardiolipin antibodies led to the diagnosis of antiphospholipid syndrome (APS). After thrombotest values had decreased to 30% (international normalized ratio: 1.5) with warfarin, her symptoms did not recur. This suggests that anticoagulant therapy is effective for the prevention of recurrence of ischemic events complicated by primary APS, even when they occur repeatedly.

Topics: Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Ischemic Attack, Transient; Lupus Coagulation Inhibitor; Recurrence; Warfarin

Cardiac causes of stroke account for approximately 20% of strokes occurring in the United States. Transthoracic echocardiography (TTE) remains the cornerstone of non-invasive cardiac imaging, but transesophageal echocardiography (TEE) is superior for identifying potential cardiac sources of emboli, including left atrial thrombi, valvular vegetations, thoracic aortic plaque, patent foramen ovale, and spontaneous left atrial echocardiographic contrast. The diagnostic yield of TEE for potential cardiac causes of thromboembolism exceeds 50%. The impact of TEE on the clinical management of this group, however, remains undefined for most TEE-specific diagnoses. Thus, routine use of TEE in these patients has been questioned. The diagnostic yield is highest if the clinical history/physical examination suggests a cardiac source. However, the clinical scenario often dictates patient management, and TEE data are used to "validate" the clinical impression. Data from large, prospective, randomized (aspirin/warfarin) studies, in which TEE data are obtained from patients with suspected cardiac thromboembolism, are needed. If specific TEE diagnoses can be identified in which defined therapies are beneficial, "source of embolism" will continue to be the most common indication for TEE referral. In this paradigm, TEE (without initial TTE) will probably become a more direct diagnostic pathway. However, if these studies demonstrate that all patients with suspected cardiac source benefit from one (or no) therapy, independent of TEE data, referrals for TEE will decline. Results of ongoing randomized trials to evaluate the efficacy of TEE in patients with cryptogenic stroke or transient ischemic attack are awaited.

Topics: Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Aspirin; Cerebrovascular Disorders; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Medical History Taking; Physical Examination; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Referral and Consultation; Reproducibility of Results; Thrombosis; Treatment Outcome; Warfarin

Warfarin prophylaxis in patients with nonvalvular atrial fibrillation may be one of the most valuable public-health interventions. Barriers to its optimal utilization include wariness about bleeding complications and concern about age-related sensitivity to the drug. The risks, however, may be minimized by creation of anticoagulation clinics to ensure optimal dosing and follow-up.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Decision Trees; Humans; Ischemic Attack, Transient; Public Health; Risk Factors; Warfarin

Stroke is ideally suited for prevention. It has a high prevalence, burden of illness, and economic cost, and safe and effective prevention measures. The estimated $30 billion that is being spent for stroke each year in the United States should not come as a surprise given the approximately 3 million stroke survivors and 400,000 to 500,000 new or recurrent stroke cases annually. Stroke remains the third leading cause of death among adults and has been targeted for cost containment by managed care health systems and other insurers. The US Public Health Service in conjunction with the National Health Promotion and Disease Prevention Objectives has set a goal to reduce stroke deaths to 20 per 100,000 by the year 2000. This goal could be attained as the estimate of "preventable" strokes could be as high as 80%. In this article, I will review the status of stroke risk factors, prevention approaches to reduce stroke, clinical trial data from primary and secondary stroke prevention studies, and future directions in stroke prevention.

Topics: Alcohol Drinking; Aspirin; Carotid Stenosis; Cerebrovascular Disorders; Clinical Trials as Topic; Diabetes Complications; Exercise; Female; Heart Diseases; Humans; Hypertension; Ischemic Attack, Transient; Male; Platelet Aggregation Inhibitors; Risk Factors; Smoking; Warfarin

To review the effectiveness of medical treatments for stroke prevention in patients at elevated risk for stroke.. English-language articles published after 1977 and indexed in MEDLINE under the following Medical Subject Heading terms: anticoagulants, aspirin, dipyridamole, ticlopidine, or sulfinpyrazone, combined with cerebrovascular disorders.. Randomized controlled trials of anticoagulant or platelet antiaggregant treatment reporting subsequent stroke and myocardial infarction, death, or complications in persons with asymptomatic carotid stenosis or bruit, transient ischemic attack (TIA), previous stroke, nonvalvular atrial fibrillation, or other vascular diseases.. Of 900 articles identified, 33 were selected by two independent reviewers and abstracted for outcome events and person-years of follow-up.. In patients with nonvalvular atrial fibrillation, warfarin is highly effective in reducing stroke and death but may result in more complications. Aspirin appears to be less effective and less risky than anticoagulation. In patients with TIA or minor stroke, both aspirin and ticlopidine reduce the risk for stroke. In patients who have had myocardial infarction, warfarin is effective but had high complication rates in the reviewed studies. Aspirin slightly reduces the risk for stroke.. Warfarin is strongly recommended for persons with nonvalvular atrial fibrillation who are older than 60 years or who have additional risk factors for stroke. Aspirin is recommended for persons at elevated risk for bleeding while receiving anticoagulants. For persons with TIA or minor stroke, aspirin should be used first. Patients who do not respond to or tolerate aspirin or who have had a major stroke are reasonable candidates for ticlopidine. For patients who have had myocardial infarction, aspirin is recommended for the prevention of secondary myocardial infarction but not of stroke.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Ischemic Attack, Transient; Myocardial Infarction; Recurrence; Risk Factors; Ticlopidine; Warfarin

Antiplatelet therapy is clearly indicated for long-term secondary prevention after transient ischemic attack and ischemic stroke. In stroke-free patients with atrial fibrillation, oral anticoagulants reduce the risk of stroke, and antiplatelet agents may be a lower risk alternative. For the early treatment of the acute phase of ischemic stroke, the role of antiplatelet and anticoagulant therapy is unclear, but is being evaluated in large clinical trials.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Warfarin

There have been major recent advances in the investigation and treatment of transient ischaemic attacks, which represent an important prodrome of cerebral infarction. Medical therapy with aspirin reduces stroke risk, while warfarin has an important place in the prevention of cardiogenic cerebral embolism. Carotid endarterectomy is of proven value in symptomatic patients with severe carotid stenosis.

Topics: Aspirin; Diagnosis, Differential; Endarterectomy, Carotid; Humans; Ischemic Attack, Transient; Warfarin

Topics: Arterial Occlusive Diseases; Aspirin; Carotid Artery Diseases; Cerebrovascular Disorders; Dipyridamole; Endarterectomy; Female; Heparin; Humans; Ischemic Attack, Transient; Male; Risk; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Mitral Valve; Myocardial Infarction; Rheumatic Heart Disease; Warfarin

Topics: Animals; Antidepressive Agents, Tricyclic; Aspirin; Blindness; Blood Platelets; Cerebrovascular Disorders; Clinical Trials as Topic; Clofibrate; Dipyridamole; Drug Therapy, Combination; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Pyrimidines; Retrospective Studies; Sulfinpyrazone; Thromboembolism; Warfarin

Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI).. Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE).. In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded.. Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo.. Major or clinically relevant nonmajor (CRNM) bleeding.. Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant).. The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status.. ClinicalTrials.gov Identifier: NCT02415400.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Percutaneous Coronary Intervention; Prospective Studies; Pyrazoles; Pyridones; Stroke; Thromboembolism; Warfarin

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Topics: Administration, Oral; Aspirin; Atrial Fibrillation; Atrial Flutter; Bioprosthesis; Brazil; Cause of Death; Creatinine; Embolism; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Mitral Valve; Rivaroxaban; Sample Size; Stroke; Surgical Procedures, Operative; Thrombosis; Treatment Outcome; Warfarin

To date, vitamin K antagonists are the only available oral anticoagulants in patients with mechanical heart valves. In this way, we developed a pilot trial with rivaroxaban..  The RIWA study was a proof-of-concept, open-label, randomized clinical trial and was designed to assess the incidence of thromboembolic and bleeding events of the rivaroxaban-based strategy (15 mg twice daily) in comparison to dose-adjusted warfarin. Patients were randomly assigned in a 1:1 ratio and were followed prospectively for 90 days..  A total of 72 patients were enrolled in the present study. Of these, 44 patients were randomized: 23 patients were allocated to the rivaroxaban group and 21 to the warfarin group. After 90 days of follow-up, the primary outcome occurred in one patient (4.3%) in the rivaroxaban group and three patients (14.3%) in the warfarin group (risk ratio [RR] 0.27; 95% confidence interval [CI] 0.02-2.85; P = 0.25). Minor bleeding (without discontinuation of medical therapy) occurred in six patients (26.1%) in the rivaroxaban group versus six patients (28.6%) in the warfarin group (RR 0.88; 95% CI 0.23-3.32; P = 0.85). One patient in the warfarin group died from myocardial infarction. No cases of hemorrhagic stroke, valve thrombosis, peripheral embolic events, or new intracardiac thrombus were related in both groups.. In this pilot study, rivaroxaban 15 mg twice daily had thromboembolic and bleeding events similar to warfarin in patients with mechanical heart valves. These data confirm the authors' proof-of-concept and suggest that a larger trial with a similar design is not unreasonable. CLINICALTRIAL.. NCT03566303.

Topics: Adult; Brain Infarction; Dose-Response Relationship, Drug; Embolism; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pilot Projects; Rivaroxaban; Stroke; Thromboembolism; Warfarin

The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome. In addition, there was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban compared with warfarin.. In this subanalysis of the J-ROCKET AF trial, we investigated the consistency of safety and efficacy profile of rivaroxaban versus warfarin among the subgroups of patients with previous stroke, transient ischemic attack, or non-central nervous system systemic embolism (secondary prevention group) and those without (primary prevention group).. Patients in the secondary prevention group were 63.6% of the overall population of J-ROCKET AF. In the secondary prevention group, the rate of the principal safety outcome (% per year) was 17.02 in rivaroxaban-treated patients and 18.26 in warfarin-treated patients (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.70-1.29), while the rate of the primary efficacy endpoint was 1.66 in rivaroxaban-treated patients and 3.25 in warfarin-treated patients (HR 0.51; 95% CI 0.23-1.14). There were no significant interactions in the principal safety and the primary efficacy endpoints of rivaroxaban compared to warfarin between the primary and secondary prevention groups (P=.090 and .776 for both interactions, respectively).. The safety and efficacy profile of rivaroxaban compared with warfarin was consistent among patients in the primary prevention group and those in the secondary prevention group.

Topics: Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Morpholines; Prospective Studies; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Treatment Outcome; Warfarin

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA).. In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767.. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08).. There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF.. Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Humans; Intention to Treat Analysis; Ischemic Attack, Transient; Morpholines; Multicenter Studies as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Treatment Outcome; Warfarin

The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke.. We conducted a multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.. A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.. In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov number, NCT00201461.).

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Clopidogrel; Combined Modality Therapy; Drug Therapy, Combination; Embolism, Paradoxical; Female; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Prostheses and Implants; Secondary Prevention; Stroke; Ticlopidine; Warfarin; Young Adult

The CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke or transient ischemic attack [2 points]) scoring scheme has been found to be a good predictor of stroke risk in patients with nonvalvular atrial fibrillation (AF). However, the value of the CHADS(2) scoring system in the risk stratification of patients with AF who undergo direct-current cardioversion has not yet been specifically investigated. In this study, a subgroup of 541 patients from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study who had AF for >48 hours and planned to undergo transesophageal echocardiography before direct-current cardioversion were enrolled. Each patient had a CHADS(2) score calculated. Of the patients with CHADS(2) scores of 0, 14 (10%) were found to have left atrial appendage thrombi on transesophageal echocardiography. After 6 months of follow up, patients with CHADS(2) scores of 3 to 6 showed a significantly higher mortality rate in comparison with patients with lower CHADS(2) scores (4.3% vs 0.5%, p = 0.004), despite their similar prevalence of left atrial appendage thrombus and stroke (thrombus: 13.4% vs 11.6%, p = 0.60; stroke: 0% vs 0.3%, p = 0.70). In conclusion, the CHADS(2) scoring system may be useful for predicting short-term mortality risk in patients with AF receiving elective direct-current cardioversion. However, in the preprocedural risk assessment of these patients, the CHADS(2) scoring system is not reliable in predicting risk for left atrial appendage thrombus formation, especially in patients with low CHADS(2) scores.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Electric Countershock; Female; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Risk Assessment; Stroke; Stroke Volume; Thrombosis; Tricuspid Valve Insufficiency; Warfarin

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA.. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984.. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA.. The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population.. Bristol-Myers Squibb and Pfizer.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Female; Humans; Intention to Treat Analysis; Ischemic Attack, Transient; Male; Proportional Hazards Models; Pyrazoles; Pyridones; Stroke; Treatment Outcome; Warfarin

In the Randomised Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, dabigatran reduced occurrence of both stroke and haemorrhage compared with warfarin in patients who had atrial fibrillation and were at increased risk of stroke. We aimed to assess the effects of dabigatran compared with warfarin in the subgroup of patients with previous stroke or transient ischaemic attack.. In the RE-LY trial, 18,113 patients from 967 centres in 44 countries were randomly assigned to 110 mg or 150 mg dabigatran twice daily or to warfarin dose adjusted to international normalised ratio 2·0 to 3·0. Median follow-up was 2·0 years (IQR 1·14-2·86), and the primary outcome was stroke or systemic embolism. The primary safety outcome was major haemorrhage. Patients and investigators were aware of whether patients received warfarin or dabigatran, but not of dabigatran dose, and event adjudicators were masked to treatment. In a predefined analysis, we investigated the outcomes of the RE-LY trial in subgroups of patients with or without previous stroke or transient ischaemic attack. RE-LY is registered with ClinicalTrials.gov, NCT00262600.. Within the subgroup of patients with previous stroke or transient ischaemic attack, 1195 patients were from the 110 mg dabigatran group, 1233 from the 150 mg dabigatran group, and 1195 from the warfarin group. Stroke or systemic embolism occurred in 65 patients (2·78% per year) on warfarin compared with 55 (2·32% per year) on 110 mg dabigatran (relative risk 0·84, 95% CI 0·58-1·20) and 51 (2·07% per year) on 150 mg dabigatran (0·75, 0·52-1·08). The rate of major bleeding was significantly lower in patients on 110 mg dabigatran (RR 0·66, 95% CI 0·48-0·90) and similar in those on 150 mg dabigatran (RR 1·01; 95% CI 0·77-1·34) compared with those on warfarin. The effects of both doses of dabigatran compared with warfarin were not significantly different between patients with previous stroke or transient ischaemic attack and those without for any of the outcomes from RE-LY apart from vascular death (110 mg group compared with warfarin group, interaction p=0·038).. The effects of 110 mg dabigatran and 150 mg dabigatran twice daily in patients with previous stroke or transient ischaemic attack are consistent with those of other patients in RE-LY, for whom, compared with warfarin, 150 mg dabigatran reduced stroke or systemic embolism and 110 mg dabligatran was non-inferior. [corrected] Most effects of both dabigatran doses were consistent in patients with versus those without previous stroke or transient ischaemic attack.. Boehringer Ingelheim.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibrinolytic Agents; Humans; International Cooperation; Ischemic Attack, Transient; Longitudinal Studies; Male; Pyridines; Stroke; Treatment Outcome; Warfarin

We sought to determine if patients with intracranial stenosis who have a transient ischemic attack or stroke on antithrombotic therapy are at particularly high risk for recurrent stroke.. We compared baseline features and the rates of stroke or vascular death and stroke in the territory of the symptomatic artery between patients ON (n=299) versus OFF (n=269) antithrombotics at the time of their qualifying event for the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial.. In univariate analyses, there was no difference in the rates of stroke or vascular death (21% versus 23%; hazard ratio [ON/OFF], 0.91; 95% CI, 0.64 to 1.29; P=0.59) or stroke in territory (13% versus 14%; hazard ratio [ON/OFF], 0.90; 95% CI, 0.57 to 1.39; P=0.61) between patients ON versus OFF antithrombotics at the time of their qualifying event. A multivariable analysis adjusted for the difference in risk factors between patients ON and OFF antithrombotic therapy also showed no significant differences in the combined end point of stroke or vascular death (hazard ratio [ON/OFF], 0.86; 95% CI, 0.55 to 1.34; P=0.51) or stroke in territory (hazard ratio [ON/OFF], 1.01; 95% CI, 0.58 to 1.77; P=0.97) between patients ON versus OFF antithrombotic therapy at the time of the qualifying event.. Patients with intracranial stenosis who fail antithrombotic therapy are not at higher risk of stroke than those who do not fail antithrombotic therapy. Given our finding that patients ON and OFF antithrombotic therapy are both at high risk for stroke in the territory, intracranial stenting trials should not be limited to just those who fail antithrombotic therapy.

Topics: Aged; Anticoagulants; Aspirin; Cerebrovascular Disorders; Constriction, Pathologic; Double-Blind Method; Endpoint Determination; Female; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Risk; Stroke; Treatment Outcome; Warfarin

Published data suggest that patients with cerebral ischaemia and atrial fibrillation (CIAF) have higher inhospital mortality than patients with cerebral ischaemia of arterial origin (CIAO). Data on long term risks are scarce. We compared the long term risks of death and vascular events (VE) between these groups.. We extended the follow-up of 2473 patients from the Dutch TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO) and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF). Hazard ratios (HRs) for death and VE of CIAF versus CIAO were analysed by means of Cox regression analysis and adjusted for age, sex and several cardiovascular risk factors.. After a mean follow-up of 10.1 years, 1484 patients with CIAO had died and 1336 had suffered at least one VE (377 cardiac, 455 stroke). Mean follow-up of the CIAF patients was 6.8 years; 150 patients had died and 136 had suffered at least one VE (41 cardiac, 63 stroke). Adjusted HRs (CIAF vs CIAO) were 1.46 (95% CI 1.22 to 1.74) for death, 1.49 (1.24 to 1.79) for first VE, 1.94 (1.47 to 2.55) for first stroke and 1.41 (1.01 to 1.96) for first cardiac event. These HRs were essentially the same as those for the duration of the trials.. Our study shows that the long term risk of death or vascular events is 1.5 times higher in patients with CIAF than in those with CIAO, after adjustment for differences between the groups.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cause of Death; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Death, Sudden, Cardiac; Disease-Free Survival; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Hospital Mortality; Humans; Ischemic Attack, Transient; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Netherlands; Proportional Hazards Models; Risk Factors; Warfarin

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.. We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin (target international normalized ratio, 2.0 to 3.0) or aspirin (1300 mg per day) in a double-blind, multicenter clinical trial. The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke.. After 569 patients had undergone randomization, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02), major hemorrhage (3.2 percent vs. 8.3 percent, respectively; hazard ratio, 0.39; 95 percent confidence interval, 0.18 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83).. 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.

Topics: Adult; Aged; Anticoagulants; Aspirin; Cardiovascular Diseases; Double-Blind Method; Female; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Secondary Prevention; Stroke; Warfarin

Anticoagulation reduces the risk of stroke in patients with atrial fibrillation. It is not clear whether patients who revert and are maintained in sinus rhythm should continue to receive warfarin. The recommendation is to anticoagulate these patients for a minimum of four weeks after cardioversion. Whether warfarin should be maintained for a longer period of time is unknown.. To address this question, data from the Canadian Trial of Atrial Fibrillation were reviewed. Among the 403 patients, 81.9% had at least one risk factor for stroke, of whom only 60% were on warfarin. Nine thromboembolic events occurred in nine patients (2.2%): all had at least one risk factor for stroke. Six events occurred in patients who were either not anticoagulated (n=4) or for whom the international normalization ratio was subtherapeutic (n=2). Eight of the nine patients were in sinus rhythm at the last follow-up visit before and at the time of evaluation of the thromboembolic event.. Anticoagulants are underused in atrial fibrillation patients at risk of stroke. Thromboembolic events are most often associated with suboptimal levels of anticoagulation and they occur despite the appearance of sinus rhythm maintenance.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Canada; Electric Countershock; Electrocardiography; Female; Follow-Up Studies; Heart Conduction System; Hemorrhage; Humans; Incidence; International Normalized Ratio; Ischemic Attack, Transient; Male; Middle Aged; Risk Factors; Severity of Illness Index; Statistics as Topic; Stroke; Thromboembolism; Treatment Failure; Warfarin

Patent foramen ovale (PFO) is associated with cryptogenic stroke. There is no study that assessed the effect of age on adverse event rates in cryptogenic stroke patients with PFO. The purpose of this retrospective analysis from PFO in Cryptogenic Stroke Study (PICSS) database was to assess the effect of age on the risk of adverse events in medically treated cryptogenic stroke patients with PFO.. 250 cryptogenic stroke patients from PICSS were followed-up for 24 months, with death and recurrent ischemic stroke as primary endpoints. Hazard ratios were calculated for determination of relative risk in cryptogenic stroke patients with and without PFO in 3 age groups (younger than 55, 55 to 64, and 65 years or older).. Among the 2 younger age groups, the presence of PFO did not significantly affect the risk of adverse events (P=0.15; hazard ratio=0.21; 95% CI, 0.02 to 1.78; 2-year event rates, 2.0% versus 9.3%; and P=0.70; hazard ratio=0.72; 95% CI, 0.14 to 3.73; 2-year event rates, 10.0% versus 13.9%). However, in those aged 65 years or older, the risk of adverse events was significantly higher in the patients with PFO (P=0.01; hazard ratio=3.21; 95% CI, 1.33 to 7.75; 2-year event rates 37.9% versus 14.5%).. In this exploratory analysis, the presence of PFO in the younger cryptogenic stroke patients did not increase the risk of adverse events. However, in the older patients, PFO significantly increased the risk of adverse events.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Brain Ischemia; Double-Blind Method; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Middle Aged; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk; Survival Analysis; Treatment Outcome; Warfarin

The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy.. In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death.. There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status.. The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Echocardiography, Transesophageal; Electric Countershock; Embolism; Female; Heart Atria; Heart Diseases; Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Prospective Studies; Stroke; Thromboembolism; Thrombosis; Warfarin

The Coumadin Aspirin Reinfarction Study demonstrated that combination treatment with fixed dose warfarin (1 or 3 mg) + aspirin 80 mg was not superior to aspirin 160 mg alone after myocardial infarction for reducing nonfatal reinfarction, nonfatal stroke, and cardiovascular death. In this analysis, we examined the importance of aspirin dose in the protection against the secondary end point of ischemic stroke. The comparison arms for this analysis were warfarin 1 mg + aspirin 80 mg versus aspirin 160 mg. In the Coumadin Aspirin Reinfarction Study, 2,028 patients were randomized to aspirin 80 mg plus warfarin 1 mg, and 3,393 were randomized to aspirin 160 mg alone. A predictive model for ischemic stroke was developed using the Cox proportional-hazards model. A reduced Cox proportional-hazards model was developed to test for the effect of aspirin dose on ischemic stroke in predefined subgroups. The incidence of ischemic stroke was lower in patients treated with aspirin 160 mg than in patients treated with aspirin 80 mg + warfarin 1 mg (0.6% vs 1.1%; p = 0.0534). Age, previous stroke or transient ischemic attack, and aspirin dose were independent predictors of ischemic stroke. In addition, the highest risk patients, those with Q-wave myocardial infarction and male patients, appeared to receive greater benefit from aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg. The results of this secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80 mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infarction patients.

Topics: Aged; Anticoagulants; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Secondary Prevention; Severity of Illness Index; Stroke; Survival Rate; Treatment Outcome; Warfarin

Transesophageal echocardiography (TEE) continues to play a prominent role in the evaluation of patients with unexplained cerebral ischemia. The STEPS Study Group (Significance of Transesophageal Echocardiography in the Prevention of Recurrent Stroke) was established to further examine the clinical significance of TEE findings in patients with suspected cardiac source of embolus and to assess the impact of these findings with respect to specific therapy and the prevention of recurrent events.. A total of 242 patients from 15 institutions within the United States underwent TEE study for evaluation of unexplained cerebral ischemia. Over a 1-year period, detailed follow-up was obtained with respect to recurrent stroke, transient ischemia attacks, or documented embolic events as well as detailed information concerning nonrandomized antithrombotic therapy.. Recurrent stroke occurred in 17 of 132 (13%) of the patients in the aspirin group versus 5 of 110 (5%) of the patients receiving warfarin therapy (P <.02). This decrease in cerebral ischemic events in the warfarin group was noted, despite the higher prevalence of atrial fibrillation and impaired ventricular function in the warfarin group. The selection of antithrombotic therapy appears, at least in part, to have been influenced by the TEE findings. Among patients receiving aspirin, a higher recurrent stroke rate was noted in those with left ventricular enlargement and atherosclerotic aortic plaque.. Abnormalities are commonly found by TEE in patients with unexplained cerebral ischemia. Patients with left ventricular enlargement and demonstrable aortic plaque on TEE study are at increased risk for recurrent stroke when receiving aspirin therapy alone. Empiric therapy with systemic anticoagulation may be indicated in patients with stroke unexplained by carotid atherosclerotic disease.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Cerebrovascular Disorders; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Recurrence; United States; Warfarin

We explored the feasibility of using subcutaneous low-molecular-weight-heparin (LMWH) injections in place unfractionated heparin (UFH) while anticoagulating patients with cerebral ischemia. In this open-labeled, prospective study, patients admitted to our hospital with transient ischemic attacks or stroke requiring anticoagulation who were otherwise medically fit for discharge home were enrolled. The LMWH nadroparin (Fraxiparine) 4100 antiXa BID was administered. In those on UFH, this was stopped after the first dose of LMWH. Patients were sent home and LMWH was administered on an outpatient basis with simultaneous oral warfarin titration till INR reached 2.0. Fifteen patients (13 inpatients, two outpatients) were enrolled; 12 had stroke, one each had crescendo transient ischaemia attacks (TIAs) while on aspirin, TIAs and intracranial arterial stenosis, TIA and atrial fibrillation. Inpatients were discharged home within a median of 1 day (range 1-3 days). Median duration of LMWH therapy was 9 days (range 4-47 days); nine required LMWH for 10 days or less. Two patients reported bruising at the injection site. There was no death, cerebral ischaemia recurrence or major hemorrhage. Using LMWH in place of UFH in patients with cerebral ischaemia is a feasible and safe way of achieving optimal oral anticoagulation and can be done on an outpatient basis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Brain Ischemia; Feasibility Studies; Female; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Ischemic Attack, Transient; Male; Middle Aged; Outpatients; Prospective Studies; Treatment Outcome; Warfarin

We compared the efficacy of very-low-intensity oral anticoagulation (OA) with that of the recommended standard low-intensity oral anticoagulation, using international normalized ratios (INRs). We enrolled 101 patients into a pilot study--51 patients in the very-low-intensity anticoagulation arm (INR 1.4 to 2.0) and 50 in the standard low-intensity anticoagulation arm (INR 2.0 to 3.0). They were monitored for thrombotic/embolic and hemorrhagic complications for an average follow-up of 1.5 years. Two thrombotic/embolic events occurred in the very-low-intensity group; no thrombotic/embolic events occurred in the standard low-intensity group. No major bleeding occurred in the very-low-intensity group; one major hemorrhagic event occurred in the standard low-intensity group. These findings did not achieve a statistically significant difference in major complications between the two groups. It appears that very-low-intensity OA (INR 1.4 to 2.0) is as effective in preventing thromboses as standard low-intensity OA (INR 2.0 to 3.0).

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Monitoring; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Patient Compliance; Pilot Projects; Pulmonary Embolism; Recurrence; Thrombophlebitis; Thrombosis; Warfarin

Topics: Clinical Trials as Topic; Dicumarol; Drug Evaluation; Humans; Ischemic Attack, Transient; Protein Binding; Warfarin

Topics: Animals; Antidepressive Agents, Tricyclic; Aspirin; Blindness; Blood Platelets; Cerebrovascular Disorders; Clinical Trials as Topic; Clofibrate; Dipyridamole; Drug Therapy, Combination; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Pyrimidines; Retrospective Studies; Sulfinpyrazone; Thromboembolism; Warfarin

The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.

Topics: Adult; Age Factors; Anticoagulants; Carotid Artery, Internal; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Phenindione; Prognosis; Radiography; Sex Factors; Time Factors; Warfarin

The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function.. We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category.. DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Kidney; Retrospective Studies; Stroke; Warfarin

It is unclear whether warfarin treatment with high time in therapeutic range (TTR) is as effective and safe as non-vitamin K antagonist oral anticoagulants (NOACs). It is crucial to compare warfarin with effective TTR and NOACs to predict long-term adverse events in patients with atrial fibrillation.. We aimed to compare the long-term follow-up results of patients with atrial fibrillation (AF) who use vitamin K antagonists (VKAs) with effective TTR and NOACs.. A total of 1140 patients were followed at 35 different centers for five years. During the follow-up period, the international normalized ratio (INR) values were studied at least 4 times a year, and the TTR values were calculated according to the Roosendaal method. The effective TTR level was accepted as >60% as recommended by the guidelines. There were 254 patients in the effective TTR group and 886 patients in the NOAC group. Ischemic cerebrovascular disease/transient ischemic attack (CVD/TIA), intracranial bleeding, and mortality were considered primary endpoints based on one-year and five-year follow-ups.. Ischemic CVD/TIA (3.9% vs. 6.2%; P = 0.17) and intracranial bleeding (0.4% vs. 0.5%; P = 0.69), the one-year mortality rate (7.1% vs. 8.1%; P = 0.59), the five-year mortality rate (24% vs. 26.3%; P = 0.46) were not different between the effective TTR and NOACs groups during the follow-up, respectively. The CHA2DS2-VASC score was similar between the warfarin with effective TTR group and the NOAC group (3 [2-4] vs. 3 [2-4]; P = 0.17, respectively). Additionally, survival free-time did not differ between the warfarin with effective TTR group and each NOAC in the Kaplan-Meier analysis (dabigatran; P = 0.59, rivaroxaban; P = 0.34, apixaban; P = 0.26, and edoxaban; P = 0.14).. There was no significant difference in primary outcomes between the effective TTR and NOAC groups in AF patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Ischemic Attack, Transient; Pyridones; Rivaroxaban; Stroke; Warfarin

We studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin.. This was a retrospective nested case-control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up.. National FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007-31 December 2011.. A total of 54 568 warfarin-anticoagulated patients.. The number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111-141 g/L vs 123-147 g/L, p<0.001), while patients with stroke/TIA had only modestly lower INR (median 2.2 vs 2.3; 1.8-2.6 vs 2.1-2.7, p<0.001). When the last measured haemoglobin was below the reference value (130 g/L for men, 120 g/L for women), the OR for a bleeding complication was 2.9 and stroke/TIA, 1.5. If the haemoglobin level was below 100 g/L, the complication risk increased further by 10-fold. If haemoglobin values were repeatedly (more than five times) low during the preceding 3 months, future OR was for bleeds 2.3 and for stroke/TIA 2.4.. The deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.

Topics: Anemia; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Female; Hemoglobins; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Registries; Retrospective Studies; Stroke; Thrombosis; Treatment Outcome; Warfarin

Limited literature has established the role of direct oral anticoagulants (DOAC) for elderly patients with nonvalvular atrial fibrillation who are unsuited for warfarin. Therefore, the objectives of this study were to assess the effectiveness and safety of DOAC use in this vulnerable patient population. This was a retrospective propensity score matching cohort study. Among all patients aged 75+ years who were not candidates for warfarin, we matched those who initiated DOAC between September 2017 and September 2018 with those who did not receive DOAC or warfarin in a 1:1 ratio. Effectiveness outcome was a composite measure of stroke, transient ischemic attack, and pulmonary embolism. Safety outcome was a composite measure of non-trauma-related intracranial hemorrhage and gastrointestinal bleed. Unless patients died or lost membership, follow-up period for the effectiveness outcome was until the end of 2019, whereas the safety outcome was for a period up to 1 year. Conditional logistic regression was used to analyze both outcomes. We identified 7818 patients who met the inclusion criteria and started DOAC, which matched to 7818 patients who did not receive anticoagulants. The mean age was 82.3 ± 5.1 years, and 51.5% male. The DOAC group had a lower hazard ratio of 0.37 (confidence interval, 0.24-0.57; P < 0.01) for composite effectiveness outcomes, whereas no difference in the composite safety outcome (hazard ratio, 0.91; confidence interval, 0.65-1.25; P = 0.55) when compared with matched control. In conclusion, DOAC was found to be effective in preventing thromboembolic events in patients aged 75+ years with nonvalvular atrial fibrillation who were not eligible for warfarin.

Topics: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Contraindications, Drug; Cost-Benefit Analysis; Drug Costs; Factor Xa Inhibitors; Female; Humans; Ischemic Attack, Transient; Male; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

We determined the long-term event incidence among elderly patients with nonvalvular atrial fibrillation in terms of history of stroke/transient ischemic attack (TIA) and oral anticoagulation.. Patients aged ≥75 years with documented nonvalvular atrial fibrillation enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were divided into 2 groups according to history of stroke/TIA. The primary end point was the occurrence of stroke/systemic embolism within 2 years, and secondary end points were major bleeding and all-cause death within 2 years. Cox models were used to determine whether there was a difference in the hazard of each end point in patients with/without history of stroke/TIA, and in ischemic stroke/TIA survivors taking direct oral anticoagulants versus those taking warfarin.. Of 32 275 evaluable patients (13 793 women [42.7%]; median age, 81.0 years), 7304 (22.6%) had a history of stroke/TIA. The patients with previous stroke/TIA were more likely to be male and older and had higher hazard rates of stroke/systemic embolism (adjusted hazard ratio, 2.25 [95% CI, 1.97-2.58]), major bleeding (1.25, 1.05-1.49), and all-cause death (1.13, 1.02-1.24) than the other groups. Of 6446 patients with prior ischemic stroke/TIA, 4393 (68.2%) were taking direct oral anticoagulants and 1668 (25.9%) were taking warfarin at enrollment. The risk of stroke/systemic embolism was comparable between these 2 groups (adjusted hazard ratio, 0.90 [95% CI, 0.71-1.14]), while the risk of major bleeding (0.67, 0.48-0.94), intracranial hemorrhage (0.57, 0.39-0.85), and cardiovascular death (0.71, 0.51-0.99) was lower among those taking direct oral anticoagulants.. Patients aged ≥75 years with nonvalvular atrial fibrillation and previous stroke/TIA more commonly had subsequent ischemic and hemorrhagic events than those without previous stroke/TIA. Among patients with previous ischemic stroke/TIA, the risk of hemorrhagic events was lower in patients taking direct oral anticoagulants compared with warfarin.. URL: https://www.. gov; Unique Identifier: UMIN000024006.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Evidence-based stroke clinical practice guidelines provide guidance as how to best manage patients with cerebrovascular disease. Where there are grey zones, the clinician decides what she/he feels is the most appropriate in that circumstance. This study was performed to determine how adult neurologists in Singapore would use antiplatelets(AP) and anticoagulants(AC) for their ischemic stroke patients in various settings where the evidence is uncertain.. A standardised questionnaire was sent to adult neurologists in Singapore. The questions evaluated their preferred type and dose of AP, use of heparin prior to initiating warfarin, and their preferred treatments in 6 different clinical scenarios.. A total of 31/33 neurologists responded (93.9%). For long term secondary prevention, 71.0% preferred aspirin only, 22.6% clopidogrel/ticlopidine only, 6.5% aspirin plus dipyridamole. Anticoagulation with warfarin was initiated with a heparin bolus by 45.2%. AC were preferred by 80.6% for stroke in evolution, 80.6% for presumed basilar artery thrombosis, 54.8% for crescendo TIAs. For patients awaiting CEA, 58.1% preferred AP, 32.3% AC. For patients on preferred AP developing another cerebrovascular event with no new underlying cause, 48.4% would change AP, 25.8% would add another AP. For patients on adequate AC for non-cardioembolism developing another cerebrovascular event, 54.8% would add anti-platelet, 19.4% would increase AC.. The widespread use of aspirin for long-term secondary prevention is similar to other countries. The variation in the use of antithrombotic agents in other settings may reflect the lack of sufficient evidence to guide therapy in the various specific stroke patient management scenarios.. neurologist, practice, antiplatelet, anticoagulant, stroke, cerebrovascular disease.

Topics: Adult; Anticoagulants; Aspirin; Cerebrovascular Disorders; Female; Heparin; Humans; Ischemic Attack, Transient; Ischemic Stroke; Neurologists; Platelet Aggregation Inhibitors; Singapore; Stroke; Surveys and Questionnaires; Warfarin

To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke.. A comparative cohort study in UK general practice data from The Health Improvement Network database.. Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date.. The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint.. Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75).. Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Hemorrhage; Humans; Ischemic Attack, Transient; Myocardial Infarction; Primary Health Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United Kingdom; Warfarin

Atrial fibrillation (AF) is common in patients with transthyretin cardiac amyloidosis (ATTR-CA). The optimal strategy to prevent strokes in patients with ATTR-CA and AF is unknown.. To compare outcomes in patients with ATTR-CA and AF treated with warfarin versus novel oral anticoagulants (NOACs).. This study was a retrospective analysis of patients with ATTR-CA stratified by presence or absence of AF and anticoagulation therapy. The primary outcome included a time to event analysis for the combined outcomes of stroke, transient ischaemic attack (TIA), major bleed, or death.. Patient with ATTR-CA and AF are at increased risk for stroke compared to patients with ATTR-CA and without AF. Thrombotic events and major bleeds did not differ between those who received warfarin and NOACs.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Stroke; Thrombosis; Warfarin

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Mass Index; Coronary Disease; Dabigatran; Diabetes Mellitus; Embolism; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Male; Medication Adherence; Middle Aged; Polypharmacy; Proportional Hazards Models; Stroke; Warfarin

Clinical and imaging characteristics of patients receiving direct oral anticoagulants presenting with transient ischaemic attack or stroke are lacking. A retrospective review of all patients who presented to a high-volume primary stroke centre with acute stroke symptoms while prescribed an oral anticoagulant between January 2012 and June 2017. Clinical, radiological characteristics and functional outcomes were examined. Anticoagulated patients diagnosed with stroke or transient ischaemic attack shared similar disease and outcome characteristics irrespective of anticoagulants used. One-third of warfarin patients with sub-therapeutic international normalised ratios were treated with thrombolytics but no direct oral anticoagulants level was performed in any of the patients, with only one treated by intravenous thrombolysis.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Male; Retrospective Studies; Stroke; Warfarin

It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between atrial fibrillation patients with and without a history of stroke or transient ischemic attack (TIA). Using 2012 to 2014 Medicare claims data, we identified patients newly diagnosed with AF in 2013 to 2014 who initiated apixaban, dabigatran, rivaroxaban, or warfarin. We categorized patients based on a history of stroke or TIA. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. DOACs were generally more effective than warfarin in stroke prevention; however, there were important differences between subgroups defined by a history of ischemic stroke. In particular, the superiority of dabigatran compared with warfarin in ischemic stroke prevention was more pronounced in patients with a history of stroke or TIA (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48 to 0.85) than in patients with no history of stroke or TIA (HR 0.94; 95% CI 0.75 to 1.16; p value for interaction = 0.034). There was no difference in the risk of stroke between apixaban, dabigatran, and rivaroxaban in patients with no history of stroke or TIA. However, in patients with a history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64; 95% CI 0.48 to 0.85) and rivaroxaban (HR 0.70; 95% CI 0.56 to 0.87), compared with apixaban (p value for both interactions <0.05). In conclusion, the comparative effectiveness of DOACs differs substantially between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Medicare; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cause of Death; Female; Follow-Up Studies; Humans; Incidence; Ischemic Attack, Transient; Japan; Male; Retrospective Studies; Survival Rate; Time Factors; Warfarin

Patients on anticoagulant or antiplatelet therapy are often required to discontinue these medications before and during surgical or invasive procedures. In some cases, the patient stops the treatment without medical supervision. These situations may increase stroke risk. To identify the ischemic stroke and transient ischemic attack (TIA) prevalence related to length of time of discontinuation of antiplatelet or vitamin K antagonist therapy, in a group of inpatients from a specialized neurological hospital in Brazil.. Cross-sectional, retrospective and descriptive study of stroke inpatients for three years. Medical reports were reviewed to find study participants, stroke characteristics, risk factors, reasons and time of drug interruption.. In three years, there were 360 stroke and TIA inpatients, of whom 27 (7.5%) had a history of antiplatelet or vitamin K antagonist interruption correlated with the time of the event (81% ischemic stroke, 19% TIA). The median time between antiplatelet interruption and an ischemic event was five days, and 62% of events occurred within seven days after drug suspension. For vitamin K antagonists, the average time to the ischemic event was 10.4 days (SD = 5.7), and in 67% of patients, the time between drug discontinuation and the event was 7-14 days. The most frequent reason for drug suspension was patient negligence (37%), followed by planned surgery or invasive examination (26%) and side effects, including hemorrhage (18.5%).. Antiplatelet or vitamin K antagonist suspension has a temporal relationship with the occurrence of stroke and TIA. Since these events are preventable, it is crucial that healthcare professionals convince their patients that drug withdrawal can cause serious consequences.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brazil; Clopidogrel; Cross-Sectional Studies; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stroke; Warfarin

Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR).. We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin.. FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003-2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH.. A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18-4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51-4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11-0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23-2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32-14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30-0.91) and high INR (OR: 0.40, 95% CI: 0.33-0.48) were overrepresented in patients with ICH.. In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Cerebral Hemorrhage; Chi-Square Distribution; Comorbidity; Drug Monitoring; Female; Finland; Heart Failure; Humans; Hypercholesterolemia; International Normalized Ratio; Ischemic Attack, Transient; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Registries; Renal Insufficiency; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Stroke; Warfarin

Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Follow-Up Studies; Humans; Infections; Ischemic Attack, Transient; Japan; Male; Middle Aged; Prospective Studies; Registries; Stroke; Survival Analysis; Treatment Outcome; Warfarin

We recently measured the longitudinal use of secondary prevention medication following hospital discharge and the factors influencing persistence in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) in China.. Patients with AIS and TIA who were enrolled in the China National Stroke Registry II from June 2012 to January 2013 were surveyed to determine persistence. The medications included antiplatelet therapies, warfarin, antihypertensive therapies, statins, and diabetes medications. We determined persistence for a three-month period following discharge. Persistence was defined as the continuation of all secondary preventive medications prescribed upon hospital discharge. The factors associated with medication persistence 3 months after discharge were examined using a multivariable logistic regression.. Of the 21,592 patients with AIS and TIA, 18,344 (91.2%) were eligible for analysis. After 3 months post-discharge, 46.2% of the subjects continued to take all secondary prevention medications prescribed at discharge. Independent predictors of three-month medication persistence included younger age, absence of a history of diabetes or atrial fibrillation, higher family income, less severe stroke, index cerebrovascular event of ischemic stroke, and being treated in a hospital with a stroke unit and more beds in the neurology department.. More than half of patients with AIS and TIA reported discontinuing one or more secondary prevention medications within 3 months of hospital discharge. Several factors associated with medication persistence were identified. Here, we propose strategies that could be implemented to improve the quality of secondary prevention.

Topics: Age Distribution; Aged; Atrial Fibrillation; China; Female; Hospitalization; Humans; Ischemic Attack, Transient; Male; Medication Adherence; Middle Aged; Registries; Secondary Prevention; Stroke; Warfarin

Cardiac papillary fibroelastoma is reported to be the 2nd most common cardiac tumor following myxoma. Owing to the risk of embolism, early surgical excision is the treatment of choice. We report a case of effective anticoagulation therapy prior to surgical excision of an aortic valve papillary fibroelastoma. A 78-year-old man was admitted to our hospital because of transient cerebral ischemic attack. The symptom was relieved in a short period. Echocardiography revealed a tumor at the aortic valve. Cardiac computed tomography revealed a sea-anemone-like appearance of the tumor. Cardiac papillary fibroelastoma was suspected on close examination. The operation was postponed because of gingivitis that required draining. During 3 months awaiting the operation, he continued receiving anticoagulation therapy, which successfully prevented thromboembolism. Administration of anticoagulation therapy may be considered, unless early surgical excision can be performed.

Topics: Aged; Aortic Valve; Fibroma; Heart Neoplasms; Humans; Ischemic Attack, Transient; Male; Papillary Muscles; Warfarin

Limited real-world data exist comparing each non-vitamin K antagonist oral anticoagulant (NOAC) to warfarin in patients with nonvalvular atrial fibrillation who have had a previous ischemic stroke or transient ischemic attack.. Using MarketScan claims from January 2012 to June 2015, we identified adults newly initiated on oral anticoagulation, with ≥2 diagnosis codes for nonvalvular atrial fibrillation, a history of previous ischemic stroke/transient ischemic attack, and ≥180 days of continuous medical and prescription benefits before anticoagulation initiation. Three analyses were performed comparing 1:1 propensity score-matched cohorts of apixaban versus warfarin (n=2514), dabigatran versus warfarin (n=1962), and rivaroxaban versus warfarin (n=5208). Patients were followed until occurrence of a combined end point of ischemic stroke and intracranial hemorrhage (ICH) or major bleed, switch/discontinuation of index oral anticoagulation, insurance disenrollment, or end of follow-up. Mean follow-up was 0.5 to 0.6 years for all matched cohorts.. Using Cox regression, neither apixaban nor dabigatran reduced the combined primary end point of ischemic stroke or ICH (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.33-1.48 and HR, 0.53; 95% CI, 0.26-1.07) and had nonsignificant effect on hazards of major bleeding (HR, 0.79; 95% CI, 0.38-1.64 and HR, 0.58; 95% CI, 0.26-1.27) versus warfarin. Rivaroxaban reduced the combined end point of ischemic stroke or ICH (HR, 0.45; 95% CI, 0.29-0.72) without an effect on major bleeding (HR, 1.07; 95% CI, 0.71-1.61). ICH occurred at rates of 0.16 to 0.61 events per 100 person-years in the 3 NOAC analyses, with no significant difference for any NOAC versus warfarin.. Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Cerebral Hemorrhage; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Echocardiography; Endocarditis; Female; Heart Valve Diseases; Humans; Ischemic Attack, Transient; Lupus Erythematosus, Systemic; Tricuspid Valve; Warfarin

To determine the effect of new oral anticoagulants (NOACs) on prescribing practices in older adults with atrial fibrillation (AF).. Retrospective observational cohort study.. Academic medical center in St. Louis, Missouri.. Individuals aged 75 and older with AF admitted to the hospital from October 2010 through September 2015 (N = 6,568, 50% female, 15% non-white).. Information on NOACs and warfarin prescribed at discharge was obtained from hospital discharge summaries, and linear regression was used to examine quarterly trends in their use. Multivariable logistic regression was used to assess independent predictors of anticoagulant use.. NOAC use increased over time (correlation coefficient (r) = 0.87, P < .001), warfarin use did not change (r = -0.16, P = .50), and overall anticoagulant use (NOACs and warfarin) increased (r = 0.68, P = .001). NOAC use increased over time in all age groups (75-79, 80-84, 85-89) except aged 90 and older, but increasing age attenuated the rate of NOAC uptake. There was no consistent relationship between age and warfarin or overall anticoagulant use, except that individuals aged 90 and older had consistently lower use. Overall, fewer than 45% of participants were prescribed an anticoagulant. In multivariable analysis, younger age, white race, female sex, higher hemoglobin, higher creatinine clearance, being on a medical service, hypertension, stroke or transient ischemic attack, no history of intracranial hemorrhage, and a modified HAS-BLED score of less than 3 increased the likelihood of receiving NOACs.. Prescription of anticoagulants for AF increased in older adults primarily because of an increase in the use of NOACs. Nonetheless, fewer than 45% of participants were prescribed an anticoagulant. Additional research is needed to optimize prescribing practices for older adults with AF.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; Ischemic Attack, Transient; Linear Models; Male; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

The safety and efficacy of the contemporary atrial fibrillation (AF) ablation in patients with a recent or previous history of cardioembolic stroke (CS) or transient ischemic attack (TIA) remain to be established.. A total of 447 patients who underwent first-ever contact force (CF)-guided AF ablation with circumferential pulmonary vein isolation were included. Of these, 17 had CS or TIA within 6 months before ablation (Group 1), 30 more than 6 months before ablation (Group 2), and the other 400 without CS or TIA (Group 3). Procedural complications and recurrence of AF and atrial tachyarrhythmias were compared among the 3 groups.. The mean age was 71±7, 66±9, and 61±11 years in Groups 1, 2, and 3, respectively (p<0.05, Group 1 versus Group 3). The oral anticoagulants were warfarin (n=108, 24.1%), dabigatran (n=101, 22.6%), rivaroxaban (n=147, 32.9%), apixaban (n=87, 19.5%), and edoxaban (n=4, 0.9%), and did not differ among the 3 groups. Median follow-up period was 14 [IQR 12-22], 13 [12-14], and 12 [10-16] months, respectively. One episode of cardiac tamponade, 2 episodes of arteriovenous fistula, and some minor complications occurred in Group 3, but no complications occurred in Groups 1 and 2 in the periprocedural period. Although one episode of CS occurred 11 days after the procedure in Group 3, there were no periprocedural CS, TIA, or major bleedings in Groups 1 and 2. AF recurrence-free rate after the procedure was 76.5%, 86.7%, and 79.1% in Groups 1, 2, and 3, respectively, and there was no difference in Kaplan-Meier curves among the 3 groups.. The safety and efficacy of CF-guided AF ablation in the era of direct oral anticoagulants in patients with a recent or previous history of CS or TIA are similar to those in patients without it.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dabigatran; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pulmonary Veins; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39;. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763;. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Recurrence; Risk Assessment; Stroke; Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Dementia; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Multivariate Analysis; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.

Topics: Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Stroke Volume; Venous Thromboembolism; Ventricular Dysfunction, Left; Ventricular Function, Left; Warfarin

The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack.. Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups.. The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08).. Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Follow-Up Studies; Humans; Incidence; Ischemic Attack, Transient; Male; Prospective Studies; Risk; Secondary Prevention; Stroke; Treatment Outcome; Warfarin

Although controversial, several prior studies have suggested that oral anticoagulants (OACs) are underused in the US atrial fibrillation (AF) population. Appropriate use of OACs is essential because they significantly reduce the risk of stroke in those with AF. In the >2 million Americans with AF, OACs are recommended when the risk of stroke is moderate or high but not when the risk of stroke is low. To quantify trends and guideline adherence, we evaluated OAC use (either warfarin or dabigatran) in a 10-year period in patients with new AF in the Veterans Health Administration.. New AF was defined as at least 2 clinical encounters documenting AF within 120 days of each other and no previous AF diagnosis (N = 297,611). Congestive Heart Failure, Hypertension, Age > 75, Diabetes, and Stroke (CHADS2) scores were determined using age and diagnoses of hypertension, diabetes, heart failure, and stroke or transient ischemic attack during the 12 months before AF diagnosis. Receipt of an OAC within 90 days of a new diagnosis of AF was evaluated using VA pharmacy data.. Overall, initiation of an OAC fell from 51.3% in 2002 to 43.1% in 2011. For patients with CHADS2 score of 0, 1, 2, 3, 4, and 5-6, the proportions of patients prescribed an OAC showed a relative decrease of 26%, 23%, 14%, 12%, 9%, and 13%, respectively (P < .001). Clopidogrel use was stable at 10% of the AF population.. Among US veterans with new AF and additional risk factors for stroke, only about half receive OAC, and the proportion is declining.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Clopidogrel; Dabigatran; Diabetes Mellitus; Female; Guideline Adherence; Heart Failure; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk; Risk Assessment; Stroke; Ticlopidine; United States; United States Department of Veterans Affairs; Warfarin

We describe management and outcomes of patients with nonvalvular atrial fibrillation (AF) in the Middle East. Consecutive patients with AF presenting to emergency departments (EDs) were prospectively enrolled. Among 1721 patients with nonvalvular AF, mean age was 59 ± 16 years and 44% were women. Comorbidities were common such as hypertension (59%), diabetes (33%), and coronary artery disease (33%). Warfarin was not prescribed to 40% of patients with Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke/TIA2 score of ≥2. One-year rates of stroke/transient ischemic attack (TIA) and all-cause mortality were 4.2% and 15.3%, respectively. Warfarin use at hospital-ED discharge was independently associated with lower 1-year rate of stroke/TIA (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.85; P = .015) and all-cause mortality (OR, 0.51; 95% CI, 0.32-0.83; P = .006). Prior history of heart failure and peripheral vascular disease was independent mortality predictors. Our patients are relatively young with significant cardiovascular risk. Their anticoagulation treatment is suboptimal, and 1-year all-cause mortality and stroke/TIA event rates are relatively high.

Topics: Adult; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Comorbidity; Emergency Service, Hospital; Female; Guideline Adherence; Humans; Ischemic Attack, Transient; Logistic Models; Male; Middle Aged; Middle East; Multivariate Analysis; Odds Ratio; Patient Discharge; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

The risk of ischemic stroke/thromboembolic events after an intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) who are on warfarin treatment is poorly characterized. The aim of this study was to assess the association between the risk of ischemic stroke/thromboembolic events and ICH.. Linkage of three Danish nationwide administrative registries in the period between 1999 and 2012 identified patients with AF on warfarin treatment. Event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched OR was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.. We studied 58,815 patients with AF (median age, 72.6 years; 60% men). When compared with the non-ICH group, the ICH group was at increased risk for stroke/systemic embolism/transient ischemic attack (TIA) (rate ratio, 3.67; 95% CI, 3.12-4.31) and mortality (rate ratio, 5.55; 95% CI, 5.20-5.92), but not for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39). The matched OR of ICH occurrences prior to a stroke/systemic embolism/TIA was 4.33 (95% CI, 2.44-8.15). The rate ratio of claimed warfarin prescriptions post- and pre-ICH event was 0.28 (95% CI, 0.24-0.33).. In this large-scale study of patients with AF treated with warfarin, first-time ICH was associated with an increased rate of ischemic stroke/systemic embolism/TIA and mortality compared with the non-ICH group. There was a decrease in the warfarin-prescription purchase rate in the post-ICH period compared with pre-ICH, which may partly explain the excess risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Denmark; Embolism; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Prevalence; Registries; Retrospective Studies; Risk Factors; Stroke; Survival Rate; Warfarin

Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.. We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.. We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006-0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18-28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861-6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216-1.89, P=0.40).. Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Middle Aged; Morpholines; Patient Readmission; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Venous Thrombosis; Warfarin; Withholding Treatment

Novel oral anticoagulant (NOAC) agents dabigatran, rivaroxaban, and apixaban are increasingly utilized as thromboembolic prevention for patients with atrial fibrillation undergoing direct current cardioversion (DCCV) with post hoc analyses of clinical trials suggesting satisfactory safety and efficacy. This study characterizes utilization, effectiveness, and complications of NOAC agents for stroke prophylaxis in the setting of DCCV.. Comparison of warfarin and NOAC agents as periprocedural anticoagulation for DCCV procedures performed at Cleveland Clinic from January 2009 through December 2013. Variables of interest include utilization rates for each NOAC agent stratified by clinical parameters including CHADS2 score, and associated clinical outcomes including cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral arterial embolism (PAE), and bleeding events during 8 weeks of postprocedure follow-up.. Among 5,320 DCCV procedures, 673 (12.6%) cases were excluded due to inadequate follow-up. Warfarin was utilized in 3,721 (80.1%), dabigatran in 719 (15.5%), rivaroxaban in 159 (3.4%), and apixaban in 48 (1.0%) with a steady increase in NOAC utilization from 2011 to 2013. There were low rates of CVA/TIA (warfarin: 0.97% vs NOAC 1.62%, P = 0.162) and bleeding (warfarin: 1.02% vs NOAC: 0.5%, P = 0.247) and no significant differences detected between agents. Higher CHADS2 /CHA2 DS2 -VASC scores were associated with thromboembolic and bleeding risk. Increasing age, chronic kidney disease, diabetes, coronary disease, and deep vein thrombosis/pulmonary embolism were associated with increased bleeding risk.. In a high-volume, single-center experience, NOAC utilization has grown to account for over a third of cardioversion procedures, and these agents appear safe and effective compared to warfarin with low rates of thromboembolic and bleeding complications.

Topics: Administration, Oral; Aged; Anticoagulants; Dabigatran; Defibrillators, Implantable; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Topics: Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Female; Humans; Ischemic Attack, Transient; Male; Registries; Stroke; Warfarin

Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack in patients with atrial fibrillation, yet diffusion of these therapies and patterns of use among atrial fibrillation patients with ischemic stroke and transient ischemic attack have not been well characterized.. Using data from Get With The Guidelines-Stroke, we identified a cohort of 61 655 atrial fibrillation patients with ischemic stroke or transient ischemic attack hospitalized between October 2010 and September 2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16% to 17% plateau during the study period, although anticoagulation rates among eligible patients did not change appreciably (93.7% versus 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% versus 40.9% with CHA2DS2-VASc ≤5, P<0.001 for difference in CHA2DS2-VASc).. NOACs have had modest but growing uptake over time among atrial fibrillation patients hospitalized with stroke or transient ischemic attack and are prescribed to patients with lower stroke risk compared with warfarin.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hospitalization; Humans; Incidence; Ischemic Attack, Transient; Male; Risk Factors; Stroke; Treatment Outcome; United States; Warfarin

Since 2010, several novel oral anticoagulants (NOACs) have been approved by the United States Food and Drug Administration for the use in the prevention of cerebrovascular accidents (CVAs) in nonvalvular atrial fibrillation.. Our aim was to describe the trends and characteristics of NOAC-related emergency department (ED) visits.. Retrospective review of data from an ED tracking system of all visits that had a medication reconciliation with an NOAC or warfarin to a tertiary care ED between October 2010 and August 2014. Basic demographics, admission rate, admission diagnoses, and trends were analyzed.. The rate of warfarin visits was stable at 50-60 patients per month (PPM) per 1000 ED visits, however, the rate of dabigatran visits rose to 3-5 PPM/1000 until 2012 and has stayed stable, while rivaroxaban and apixaban have been gradually increasing to 2-4 and 1-2 PPM/1000, respectively. The admission rate for warfarin was 63.7% and for NOACs was 58.1%, compared to baseline admission rate of 35.5%. The hemorrhagic diagnosis rate was similar for warfarin and the NOACs (8.8% and 8.0%, respectively). There were three significantly different admission diagnoses: there were more admission for atrial fibrillation (5.4% vs. 1.9%) and CVA/transient ischemic attack (5.3% vs. 3.0%) in the NOAC group, while there were more admissions for intracranial hemorrhage (2.7% vs. 0.8%) in the warfarin group.. There has been a steady increase of ED patients who are taking an NOAC. There is a nearly double admission rate for an anticoagulated patient regardless of reason for ED visit. There appears to be no difference between rates of bleeding between warfarin and NOACs, although patients taking NOACs are admitted less often for intracranial hemorrhage.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Patient Admission; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) are broadly preferable to vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (AF) given their overall net clinical benefit. We report an audit of the profile of OAC usage and adverse events in patients attending a specialist AF clinic.. Patients attending our specialist AF clinic who were commenced on NOACs for SPAF between January 2013 and August 2014 were included and electronic medical records were retrospectively reviewed between August 2014 and November 2014, to collect demographic, clinical and outcome data. Outcomes included cerebrovascular and bleeding events, death, switching between NOACs or to VKA, dose changes, cessation of NOACs and the reasons for these. To provide perspective, descriptive comparisons were made with a historical cohort of warfarin users attending the specialist AF clinic prior to the introduction of NOACs.. We report data on 813 patients as follows: (i) 233 consecutive patients (mean (standard deviation) age 74 (10) years, 45.1% female) initiated on NOACs, with median (interquartile range) CHA2 DS2 -VASc score 3 (2-5) and HAS-BLED score 1 (1-2); and (ii) a historical cohort of 580 patients on warfarin (mean (SD) age 75 (10) years, 42.1% female) with broadly similar demographics. Overall, 54.5% (127/233) were started on rivaroxaban, 22.7% (53/233) on dabigatran and 22.7% on apixaban. Two patients experienced a transient ischaemic attack; 31 patients (13%) contributed to 37 documented bleeding events of which five bleeds (in four patients, 1.7%) were classified as major. There were seven deaths; cause of death was not available for three and the others were not related to NOACs. Eighteen (7.7%) patients switched NOACs, 2 (0.9%) patients switched to warfarin and 8 (3.4%) had their NOACs stopped. There were no ischaemic strokes in the NOAC cohort, compared with nine in the warfarin cohort, with a similar rate of major bleeding (1.7% for NOACs and 1.6% for warfarin). There were more gastrointestinal haemorrhages in the NOAC cohort (3.4% vs. 0.7% with warfarin).. In this specialist AF clinic, patients prescribed NOACs had a favourable adverse event profile with good efficacy for stroke prevention, with a low rate of cessation or switch to warfarin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Clinical Audit; Dabigatran; Drug Substitution; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Warfarin

Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines.. The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers.. On enrolment, 896 (9.4 %) patients reported a prior ischaemic stroke or transient ischaemic attack. Stroke patients were significantly older, more likely to be female, had a higher rate of cardiovascular risk factors, and more frequently received anticoagulation (almost exclusively VKA) than patients without prior stroke history. Following enrolment, 76.4 % of all stroke patients without VKA contraindications received anticoagulation, which inversely associated with age (OR 0.95 per year; 95 % CI 0.92-0.97). General practitioners/internists (OR 0.40; 95 % CI 0.21-0.77) and physicians working in regional hospitals (OR 0.47; 95 % CI 0.29-0.77) prescribed anticoagulation for secondary stroke prevention less frequently than physicians working at university hospitals (reference) and office-based cardiologists (OR 1.40; 95 % CI 0.76-2.60). The impact of the treating healthcare provider was less evident in registry patients without prior stroke.. In the AFNET registry, anticoagulation for secondary stroke prevention was prescribed in roughly three-quarters of AF patients, a significantly higher rate than in primary prevention. We identified two factors associated with withholding oral anticoagulation in stroke survivors, namely higher age and-most prominently-treatment by a general practitioner/internist or physicians working at regional hospitals.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiology; Female; General Practitioners; Germany; Guideline Adherence; Hospitals; Hospitals, University; Humans; Internal Medicine; Ischemic Attack, Transient; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prospective Studies; Registries; Risk Factors; Secondary Prevention; Stroke; Survivors; Vitamin K; Warfarin; Young Adult

The objective of this study was to determine the association between warfarin discontinuation and stroke among patients with nonvalvular atrial fibrillation (NVAF).. This was a retrospective, observational study of adult NVAF patients (≥ 18 years) who were on warfarin in the Truven MarketScan commercial claims and encounters and Medicare supplemental and coordination of benefits databases (1 January 2008 to 30 June 2012). Warfarin discontinuation was defined as a gap of ≥ 45 days in warfarin prescription within 1 year after initiation. Patients who did and did not discontinue warfarin were matched at a 1:1 ratio using a propensity score method. Matched patients were followed for up to 1 year to determine risks of ischemic stroke, transient ischemic attack (TIA), and hemorrhagic stroke. A multivariate Cox proportional hazards model was used to further adjust for the effects of potential confounders.. A total of 27,000 patients were included. Patients who discontinued warfarin had higher rates of ischemic stroke compared to persistent patients (1.0 vs. 0.5 per 100 patient years, P < 0.01), but similar rates of TIA (1.2 vs. 0.9 per 100 patient years, respectively; P = 0.07) and hemorrhagic stroke (0.3 vs. 0.2 per 100 patient years, P = 0.31). After adjustment for potential confounders, warfarin discontinuation was significantly associated with increased risk of ischemic stroke (hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.47-2.84), TIA (HR: 1.36; 95% CI: 1.04-1.78), and ischemic stroke or TIA (HR: 1.50; 95% CI: 1.20-1.87).. Warfarin discontinuation is associated with increased risk of ischemic stroke and TIA. Health care providers may need to take a more active role in the management of warfarin discontinuation and clinical outcomes, e.g., by considering newer anticoagulants with favorable risk-benefit profiles. Key limitations of the study include unavailability of important clinical factors and measures in claims data.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Retrospective Studies; Stroke; Warfarin

Limited evidence exists to guide the use of early parenteral anticoagulation following mechanical heart valve replacement (MVR). The purpose of this study was to compare the 30-day rates of thrombotic and bleeding complications for MVR patients receiving therapeutic versus prophylactic dose bridging regimens. In this retrospective cohort study we reviewed anticoagulation management and outcomes of all patients undergoing MVR at five Canadian hospitals between 2003 and 2010. The primary efficacy outcome was thromboembolism (stroke, transient ischaemic attack, systemic embolism or valve thrombosis) and the primary safety outcome was major bleeding at 30-days. Outcomes were compared using a logistic regression model adjusting for propensity score and in a 1:1 propensity matched sample. A total of 1777 patients underwent mechanical valve replacement, of whom 923 received therapeutic dose bridging anticoagulation and 764 received prophylactic dose bridging postoperatively. Sixteen patients (1.8 %) who received therapeutic dose bridging and fifteen patients (2.1 %) who received prophylactic dose bridging experienced the primary efficacy outcome (odds ratio [OR] 0.90; 95 % confidence interval [CI], 0.37 to 2.18, p=0.81). Forty-eight patients (5.4 %) in the therapeutic dosing group and 14 patients (1.9 %) in the prophylactic dosing group experienced the primary safety outcome of major bleeding (OR 3.23; 95 % CI, 1.58 to 6.62; p=0.001). The direction of the effects, their magnitude and significance were maintained in the propensity matched analysis. In conclusion, we found that early after mechanical valve replacement, therapeutic dose bridging was associated with a similar risk of thromboembolic complications, but a 2.5 to 3-fold increased risk of major bleeding compared with prophylactic dose bridging.

Topics: Administration, Intravenous; Aged; Anticoagulants; Chi-Square Distribution; Drug Administration Schedule; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Logistic Models; Male; Middle Aged; Odds Ratio; Ontario; Propensity Score; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both "new starters" on dabigatran and "switchers" to dabigatran from warfarin.. We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.. Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).. In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Denmark; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Proportional Hazards Models; Registries; Secondary Prevention; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Diagnosis, Differential; Humans; Ischemic Attack, Transient; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Thrombosis; Warfarin

Atrial fibrillation (AF) imposes a substantial clinical and economic burden on the U.S. health care system. Despite national guidelines that recommend oral anticoagulation for stroke prevention, the literature consistently reports its underuse in AF patients with moderate to high stroke risk.. To assess the economic burden of underuse and nonadherence of warfarin therapy among patients with nonvalvular AF in a commercially insured population.. Claims data between January 2003 and December 2007 from the Thomson Reuters MarketScan Research Database were used. Patients diagnosed with nonvalvular AF who were continuously enrolled for at least 12 months prior to and 2 months following their diagnosis, who had a CHADS₂ score ≥ 2, and were not at high risk of bleeding (ATRIA score less than 5, HEMORR₂HAGE score less than 4, and HAS-BLED score less than 3) at baseline were included. Patients were followed for up to 18 months after the AF diagnosis date to assess the level of warfarin utilization. Health care resource utilization and cost during follow-up among patients with the proportion of days covered (PDC) by warfarin greater than 0.8 (high) and ≤ 0.8 (low) versus patients with no warfarin exposure were assessed. Multivariate negative binomial regressions and generalized linear models were used to estimate differences in resource utilization and cost, respectively.. Of the 13,289 subjects included in this analysis, 47% had no warfarin exposure; 31.5% had low PDC; and 21.5% had high PDC. The rates of ischemic stroke and transient ischemic attack (per 100 patient-years) were significantly lower for the groups that had high and low PDCs as compared with the group with no warfarin exposure (P less than 0.001). Multivariate analysis showed that patients with high PDC were 27% less likely (P less than 0.001) to incur hospitalizations, and 16% were less likely (P = 0.019) to incur emergency room visits than patients who did not receive warfarin, but the differences between low PDC patients and no warfarin exposure were not significant. Although both low and high PDC were associated with lower all-cause inpatient cost (P less than 0.001), only high PDC was associated with a lower post-index all-cause total cost (P less than 0.001) compared with no warfarin exposure.. Our results confirm that underutilization and nonadherence of warfarin among nonvalvular AF patients is both prevalent and costly. Warfarin use among patients with moderate to high stroke risk and low to moderate bleed risk demonstrated a stroke benefit without a significant increase in intracranial hemorrhage. Adherence to oral anticoagulant therapy was associated with a significant reduction in inpatient service use and total health care cost. Improving adherence to oral anticoagulation is important to attaining the clinical and economic benefits of therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cost of Illness; Databases, Factual; Emergency Service, Hospital; Female; Follow-Up Studies; Health Care Costs; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Linear Models; Male; Medication Adherence; Multivariate Analysis; Regression Analysis; Retrospective Studies; Risk Factors; Stroke; United States; Warfarin

Although atrial fibrillation (AF) is one of the most common rhythm disorders observed in clinical practice, a multicenter epidemiological study has not been conducted in our country. This study aimed to assess our clinical approach to AF based upon the records of the first multicenter prospective Atrial Fibrillation in Turkey: Epidemiologic Registry (AFTER) study.. Taking into consideration the distribution of the population in our country, 2242 consecutive patients with at least one AF attack determined by electrocardiographic examination in 17 different tertiary health care centers were included in the study. Inpatients and patients that were admitted to emergency departments were excluded from the study. Epidemiological data of the patients and the treatment administered were assessed.. The mean age of the patients was determined as 66.8 ± 12.3 years with female patients representing 60% of the study population. While the most common AF type in the Turkish population was non-valvular AF (78%), persistent/permanent AF was determined in 81% of all patients. Hypertension (%67) was the most common co-morbidity in patients with AF. While a stroke or transient ischemic attack or history of systemic thromboembolism was detected in 15.3% of the patients, bleeding history was recorded in 11.2%. Also, 50% of the patients were on warfarin treatment and 53% were on aspirin treatment at the time of the study. The effective INR level was detected in 41.3% of the patients. The most frequent cause of not receiving anticoagulant therapy was physician neglect.. These results demonstrate the necessity for improved quality of physician care of patients with AF, especially with regards to antithrombotic therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Electrocardiography; Female; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Stroke; Thromboembolism; Turkey; Warfarin; Young Adult

Topics: Anticoagulants; Biopsy; Drug Administration Schedule; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Recurrence; Risk; Stroke; Surgical Procedures, Operative; Survivors; Thromboembolism; Warfarin

Stroke prevention is a goal of atrial fibrillation (AF) management, but discontinuation of warfarin anticoagulation therapy is common.. To investigate the association between warfarin discontinuation and hospitalization for stroke among nonvalvular AF (NVAF) patients enrolled in managed care.. Patients with NVAF who initiated warfarin therapy from January 2005 through June 2009 were included. Warfarin discontinuation was defined as a supply gap >60 days without evidence of International Normalized Ratio measurements. Follow-up, which was a variable time period from warfarin initiation until the earlier of death, disenrollment from the health plan, or June 30, 2010, was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis of stroke or transient ischemic attack. Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the previous warfarin treatment period.. Among warfarin initiators with NVAF (N = 16,253), 51.4% discontinued warfarin therapy at least once during a mean follow-up of 668 days. Stroke risk was significantly greater during warfarin discontinuation periods compared with therapy periods (hazard ratio = 1.60; 95% CI, 1.35-1.90; P < 0.001).. More than half of patients on warfarin had treatment gaps or discontinued therapy. Therapy gaps were associated with increased stroke risk.

Topics: Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Hospitalization; Humans; Ischemic Attack, Transient; Male; Managed Care Programs; Medication Adherence; Middle Aged; Risk Factors; Stroke; Time Factors; Warfarin; Young Adult

The Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society jointly recommend indefinite warfarin anticoagulation in patients with CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke) score of at least 2 who have undergone ablation for atrial fibrillation. This study determined the impact of CHADS2 score on risk of late stroke or transient ischemic attack after the performance of a surgical Cox maze procedure.. A retrospective review of 433 patients who underwent a Cox maze procedure at our institution was conducted. Three months after surgery, warfarin was discontinued regardless of CHADS2 score if the patient showed no evidence of atrial fibrillation, was off antiarrhythmic medications, and had no other indication for anticoagulation. A follow-up questionnaire was used to determine whether any neurologic event had occurred since surgery.. Follow-up was obtained for 90% of the study group (389/433) at a mean of 6.6 ± 5.0 years. Among these patients, 32% (125/389) had a CHADS2 score of at least 2, of whom only 40% (51/125) remained on long-term warfarin after surgery. Six patients had late neurologic events (annualized risk of 0.2%). Neither CHADS2 score nor warfarin anticoagulation was significantly associated with the occurrence of late neurologic events. Among the individual CHADS2 criteria, both diabetes mellitus and previous stroke or transient ischemic attack were predictive of late neurologic events.. The risk of stroke or transient ischemic attack in patients after a surgical Cox maze procedure was low and not associated with CHADS2 score or warfarin use. Given the known risks of warfarin, we recommend discontinuation of anticoagulation 3 months after the procedure if the patient has no evidence of atrial fibrillation, has discontinued antiarrhythmic medications, and is without any other indication for systemic anticoagulation.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Diabetes Complications; Heart Failure; Humans; Hypertension; Ischemic Attack, Transient; Patient Acuity; Postoperative Complications; Retrospective Studies; Risk Factors; Stroke; Thromboembolism; Time Factors; Warfarin

Although a lower target prothrombin time-international normalized ratio (PT-INR) with warfarin therapy is recommended in Japan for atrial fibrillation (AF) patients ≥70 years of age, few studies have provided supporting data. The current study aimed to evaluate the clinical outcome in elderly Japanese patients with non-valvular AF who were taking warfarin.. We conducted a cohort study of 845 consecutive non-valvular AF patients ≥70 years of age who were taking warfarin (median age, 74 years; 30.5% women) with a median follow-up period of 27 months (4-69 months). Of these patients, 29.7% had a history of stoke/transient ischemic attack (TIA), and 73.1% of the patients had a CHADS(2) score ≥2. The occurrence of thromboembolic events, including ischemic stroke, TIA and other systemic embolisms, and major bleeding events were validated through a review of medical records.. The incidence of thromboembolic and major bleeding events were 3.8 and 2.1% per year, respectively. A higher incidence of both events was observed in patients with a CHADS(2) score ≥3. The multivariate analysis showed that prior stroke/TIA (odds ratio 1.7, 95% CI 1.0-2.7) and diabetes (odds ratio 1.7, 95% CI 1.0-2.8) were independent risks of thromoembolic events. A HAS-BLED score ≥3 represented a risk for major bleeding (hazard ratio 2.8, 95% CI 1.7-4.6). A PT-INR of 1.5-2.5 indicated a low incidence of thromboembolic and major bleeding events in patients with a CHADS(2) score ≥2.. Our results demonstrate that a target PT-INR of 2.0 and a range of 1.5-2.5 may be safe for elderly Japanese patients with non-valvular AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Male; Prothrombin Time; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Carotid Stenosis; Diagnosis, Differential; Female; Glucocorticoids; Heparin; Humans; Immunosuppressive Agents; Ischemic Attack, Transient; Methylprednisolone; Prednisone; Takayasu Arteritis; Treatment Outcome; Ultrasonography; Warfarin; Young Adult

The cost-effectiveness of dabigatran for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack has not been directly assessed.. A Markov decision model was constructed using data from the Randomized Evaluation of Long-Term Therapy (RE-LY) trial, other trials of warfarin therapy for atrial fibrillation, and the published cost of dabigatran. We compared the cost and quality-adjusted life expectancy associated with 150 mg dabigatran twice daily versus warfarin therapy targeted to an international normalized ratio of 2 to 3. The target population was a cohort of patients aged ≥70 years with nonvalvular atrial fibrillation, prior stroke or transient ischemic attack, and no contraindication to anticoagulation.. In the base case, dabigatran was associated with 4.27 quality-adjusted life-years compared with 3.91 quality-adjusted life-years with warfarin. Dabigatran provided 0.36 additional quality-adjusted life-years at a cost of $9000, yielding an incremental cost-effectiveness ratio of $25,000. In sensitivity analyses, the cost-effectiveness of dabigatran was inversely related to the quality of international normalized ratio control achieved with warfarin therapy. In Monte Carlo analysis, dabigatran was cost-effective in 57% of simulations using a threshold of $50,000 per quality-adjusted life-year and 78% of simulations using a threshold of $100,000 per quality-adjusted life-year.. Dabigatran appears to be cost-effective relative to warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Our analysis is limited by its reliance on data from a substudy of a single randomized trial, and our results may not apply in settings with uncommonly good international normalized ratio control using warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cohort Studies; Cost-Benefit Analysis; Dabigatran; Databases, Factual; Dose-Response Relationship, Drug; Drug Costs; Female; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Markov Chains; Models, Statistical; Monte Carlo Method; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Ischemic Attack, Transient; Morpholines; Rivaroxaban; Stroke; Thiophenes; Warfarin

Topics: Aspirin; Blood Coagulation; Cardiovascular Diseases; Coronary Artery Disease; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Period; Stroke; Thrombosis; Warfarin

Only 50% of patients who would benefit from warfarin therapy for atrial fibrillation (AF) receive treatment because of clinical concerns regarding chronic anti-coagulation. Percutaneous strategies to treat AF, including pulmonary vein isolation with a curative intent or atrioventricular nodal ablation and implantation of a permanent pacemaker for palliative rate control, have not eliminated the need to manage thromboembolic risk. With the development of a percutaneous left atrial appendage (LAA) occlusion device (the WATCHMAN percutaneous left atrial appendage occluder - Atritech Inc., Plymouth, MN, USA) for thromboembolic protection in non-valvular AF a significant therapeutic option for select patients may be available. We present the first case performed in Australia (24 November 2009) and explore this new methodology.

Topics: Aged; Anticoagulants; Aspirin; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Female; Humans; Hypertension; Ischemic Attack, Transient; Patient Preference; Risk; Risk Assessment; Septal Occluder Device; Thromboembolism; Tomography, X-Ray Computed; Ultrasonography; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Ischemic Attack, Transient; Male; Pyrazoles; Pyridones; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Ischemic Attack, Transient; Morpholines; Stroke; Thiophenes; Warfarin

Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin.. To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF.. Markov decision model.. The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom.. Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation.. Lifetime.. Societal.. Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose).. Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios.. The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran.. The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage.. Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up.. In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States.. American Heart Association and Veterans Affairs Health Services Research & Development Service.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Markov Chains; Myocardial Infarction; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Stroke; Warfarin

Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients <80 years, 110 mg bid for patients ≥80 years) versus warfarin and "real-world" prescribing (i.e. warfarin, aspirin, or no treatment in a cohort of warfarin-eligible patients) from a Canadian payer perspective. A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [primary and recurrent ischaemic strokes, systemic embolism, transient ischaemic attack, haemorrhage (intracranial, extracranial, and minor), acute myocardial infarction and death] and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospective study, published literature, and national statistics. Clinical events, summarized as events per 100 patient-years, quality-adjusted life years (QALYs), total costs, and incremental cost effectiveness ratios (ICER) were calculated. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 "real-world" prescribing) and fewer ischaemic strokes (4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 "real-world" prescribing) per 100 patient-years. The ICER of dabigatran etexilate was $10,440/QALY versus warfarin and $3,962/QALY versus "real-world" prescribing. This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients.

Topics: Aged; Atrial Fibrillation; Benzimidazoles; Canada; Computer Simulation; Cost of Illness; Cost-Benefit Analysis; Dabigatran; Embolism, Air; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Markov Chains; Pyridines; Quality-Adjusted Life Years; Stroke; Warfarin

To evaluate the impact of stopping anticoagulant medications prior to transurethral resection of the prostate on peri-operative cardiovascular complications.. Retrospective series (305 patients) undergoing TURP at a tertiary hospital between 2006 and 2010. All men were evaluated in preadmission clinics with defined protocols, with a low threshold for cardiovascular investigation. Incidence of postoperative bleeding and cardiovascular and cerebrovascular events was determined for 3 patient cohorts: group A--where anticoagulants were ceased preoperatively; group B--who were not receiving any anticoagulants; and group C--who underwent TURP while taking aspirin.. Of 305 patients, 194 (64%) did not receive anticoagulation therapy, 108 (35%) stopped receiving anticoagulation therapy pre-TURP, and 3 (0.98%) underwent TURP while taking aspirin. Anticoagulants used were aspirin (22.6%), warfarin (4.9%), antiplatelets (4.9%), and combination treatments (3.9%). Incidence of postoperative hemorrhage (early and delayed) was not significant (P = .69) between group A (10/108) and group B (7/194). Transfusion rate was 0.6% (2/305). Overall incidence of cardiovascular events was 0.98% (group A, n = 1 vs group B, n = 2), and incidence of deep vein thrombosis (0.32%; group A, n = 0 vs group B, n = 1) was not statistically significant (P = .30 and P = .37, respectively). Overall incidence of cerebrovascular events (0.65%; group A, n = 1 vs group B, n = 1) was not significant (P = 1.00). There were no deaths.. Men who have discontinue anticoagulation therapy before TURP do not appear to have a higher incidence of cardiovascular or cerebrovascular events, or bleeding-associated morbidity. It is possible that the morbidity attributed to discontinuing anticoagulation in this population may be overemphasized. Larger prospective studies are needed to better evaluate this clinical problem.

Topics: Aged; Angina Pectoris; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Blood Transfusion; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Preoperative Care; Prostatectomy; Retrospective Studies; Stroke; Venous Thrombosis; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Eye Hemorrhage; Humans; Ischemic Attack, Transient; Macular Degeneration; Male; Myocardial Ischemia; Visual Acuity; Warfarin

Current guidelines recommend stopping oral anticoagulation and starting bridging anticoagulation with intravenous heparin or subcutaneous enoxaparin when implanting a pacemaker or defibrillator in patients at moderate or high risk for thromboembolic events. A limited body of literature suggests that device surgery without cessation of oral anticoagulation may be feasible.. The purpose of this study was to evaluate the safety of device surgery in orally anticoagulated patients without interrupting warfarin therapy.. We performed a retrospective study of 459 consecutive patients on chronic warfarin therapy who underwent device surgery from April 2004 to September 2008. Warfarin was continued in 222 patients during the perioperative period. Warfarin was temporarily held and bridging therapy administered in 123 patients. Warfarin was temporarily held without bridging therapy in 114 patients.. There were no significant differences with regard to age, sex, or risk factors for thromboembolism in the three groups. Patients who continued taking warfarin had a lower incidence of pocket hematoma (P = .004) and a shorter hospital stay (P <.0001) than did patients in the bridging group. Holding warfarin without bridging is associated with a higher incidence of transient ischemic attacks (P = .01).. Temporarily interrupting anticoagulation is associated with increased thromboembolic events, whereas cessation of warfarin with bridging anticoagulation is associated with a higher rate of pocket hematoma and a longer hospital stay. Continuing warfarin with a therapeutic international normalized ratio appears to be a safe and cost-effective approach when implanting a pacemaker or defibrillator in patients with moderate to high thromboembolic risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiac Pacing, Artificial; Chronic Disease; Confidence Intervals; Defibrillators, Implantable; Enoxaparin; Female; Hemodynamics; Heparin; Humans; Incidence; International Normalized Ratio; Ischemic Attack, Transient; Length of Stay; Male; Multivariate Analysis; Perioperative Care; Registries; Retrospective Studies; Risk Factors; Thromboembolism; Time Factors; Warfarin

Topics: Adult; Aged; Aspirin; Confusion; Headache; Heparin; Humans; Ischemic Attack, Transient; Muscle Stretching Exercises; Neck; Simvastatin; Treatment Outcome; Vertebral Artery Dissection; Warfarin

Topics: Aged; Anticoagulants; Atherosclerosis; Cystitis; Diagnosis, Differential; Embolism, Cholesterol; Female; Foreign-Body Reaction; Gastrointestinal Hemorrhage; Granuloma; Hematuria; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Ischemic Attack, Transient; Risk Factors; Syndrome; Tuberculosis, Urogenital; Urinary Bladder Neoplasms; Warfarin

This paper describes the circumstances of a patient who had been receiving long-term warfarin treatment, but ceased it prior to surgical operation, sustained a transient ischemic heart attack post-operatively, which eventuated in delayed extubation and locked-in syndrome. For patients at low risk of perioperative bleeding, anticoagulation with oral vitamin K antagonist can probably be able to maintain the therapeutic range (INR ≤ 2.0) extreme. For patients with a high risk of bleeding, the international normalized ratio (INR) should be kept ≤ 1.5. Within this range, patients at low risk of thrombosis can discontinue warfarin treatment for 2-5 days pre-operatively; patients at high risk for thrombosis can stop warfarin but should probably be treated with intravenous or subcutaneous heparin when the INR is subtherapeutic.

Topics: Aged; Anticoagulants; Female; Humans; Ischemic Attack, Transient; Perioperative Period; Substance Withdrawal Syndrome; Warfarin

From April 2005 to March 2010 in the BEACH (Bettering the Evaluation and Care of Health) program, transient ischaemic attack (TIA) was managed in general practice at a rate of 2 per 1000 encounters, about 170,000 times per year nationally.

Topics: Anticoagulants; Antihypertensive Agents; Aspirin; Atorvastatin; Clopidogrel; Dipyridamole; Dopamine Antagonists; General Practitioners; Heptanoic Acids; Humans; Hypolipidemic Agents; Ischemic Attack, Transient; Perindopril; Platelet Aggregation Inhibitors; Primary Health Care; Prochlorperazine; Pyrroles; Ticlopidine; Vasodilator Agents; Warfarin

Topics: Aged; Anticoagulants; Aphasia, Broca; Atrial Fibrillation; Cerebrovascular Disorders; Female; Heparin; Humans; Ischemic Attack, Transient; Warfarin

To determine the direct healthcare costs associated with the onset of chronic nonvalvular atrial fibrillation (CNVAF), warfarin utilization and the occurrence of cerebrovascular events in a commercially-insured population.. This retrospective, observational cohort study utilized medical and pharmacy claims from a large, geographically diverse managed-care organization (N = 18.5 million) to identify continuously benefit-eligible CNVAF patients > or =45 years of age without prior valvular disease or warfarin use between January 1, 2001 and June 1, 2002. All patients were followed at least 6 months, until plan termination or the end of study follow-up. Stroke risk was assessed using the CHADS(2) (stroke-risk) index; warfarin use was defined as having filled at least one pharmacy claim. Inpatient and outpatient cost benchmarks were utilized to estimate total direct healthcare costs (pre- and post-AF index claim). For patients with transient ischemic attacks (TIA), ischemic stroke (IS) and major bleed (MB) total direct healthcare costs were also assessed. The limitations of this study included a descriptive retrospective study design without a comparison group or adjustment for baseline disease severity and drug exposure, as well as, the reliance upon administrative claims data and use of a standardized reference costing methodology.. The pre- and post-AF onset total direct healthcare costs (pmpm) for 3891 incidence CNVAF patients were $412 and $1235, respectively, a 200% increase. Of the 448 (12%) patients with a cerebrovascular event, pmpm costs post-AF ranged from $2235 to $3135 correlating with CHADS(2) stroke-risk status and exposure to warfarin. Total cohort pmpm costs pre and post event increased 24% from $3446.91 to $4262.12. Approximately 20% of all events occurred <2 days and 46% within 1 month after the index AF claim. Any warfarin exposure, regardless of CHADS(2) risk had an 18% to 29 % decrease in pmpm costs.. Post-AF total direct healthcare costs were 3 times greater than pre-AF costs. For those with a TIA, IS or MB, post-AF total direct healthcare costs increased 4.5 times from pre-AF costs; overall post-event costs in this cohort increased approximately 25% over pre-event costs. Nearly half of the events occurred within 1 month of a claim associated with an AF diagnosis. Warfarin exposure appeared to be associated with lower pmpm costs in this population.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cerebral Hemorrhage; Chronic Disease; Female; Health Care Costs; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Stroke; Warfarin

In atrial fibrillation (AF) patients stroke is nearly twice as likely to be fatal as non-AF patients and functional deficits are more likely to be severe among survivors. The incidence of stroke among AF patients is greatly reduced by oral anticoagulant treatment (OAT). However, fluctuation of anticoagulation levels is intrinsically related to OAT and often international normalized ratio (INR) is out of the therapeutic range.. Since the "anticoagulation history" is an ongoing process, we performed this prospective study in 578 AF patients to investigate the role of the whole quality of OAT and of INR levels at the occurrence of transient ischemic attack (TIA) or stroke on the severity of cerebral ischemia.. During follow-up 13 patients had TIA and 18 had stroke (rate 1.67 x 100 pt/years). In relation to the quality of anticoagulant treatment, no significant differences were found in the time spent below and within the intended therapeutic range, between patients with and without TIA/stroke. Patients with TIA/stroke spent a longer time above the intended therapeutic range with respect to other patients, even if this difference was not confirmed at multivariate analysis. Forty-six percent of patients with TIA and 66% of patients with stroke had INR>or=2 at the occurrence of ischemic event.. The severity of stroke was not related to the whole quality of anticoagulation or to INR at the event.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Confidence Intervals; Female; Humans; International Normalized Ratio; Ischemic Attack, Transient; Italy; Male; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Echocardiography, Transesophageal; Heart Septal Defects, Atrial; Humans; Ischemic Attack, Transient; Male; Middle Aged; Treatment Outcome; Warfarin

In atrial fibrillation (AF) patients, age >or=75 years is one of the major risk factors for stroke. However, it is not clear if an upper limit for the indication to OAT exists.. For this reason, we performed a prospective study on 290 AF patients on OAT aged >or=75 years (median age 82 years, total follow-up period 814 pt/years) followed by our Anticoagulation Clinic. Seventeen major bleeding events were recorded (rate 2.1 x 100 pt/years), 11 of which cerebral (1.35 x 100 pt/years). The occurrence of major bleedings was associated with history of previous TIA or stroke [OR 3.4 (1.1-12.5), p=0.01] and with diabetes [OR 4.4 (1.3-14.7) p=0.01]. We found a trend to a progressive increase in the rate of bleeding risk with the increase of the CHADS2 score: patients with score 4-6 showed a rate of 3.4 x 100 pt/years with respect to 1.5 x 100 pt/years of patients with lower score. Number Needed to Harm (NNH) was calculated in relation to different classes of age (75-89, 80-84, >or=85 years) and to CHADS2 score. For patients in CHADS2 score 1-3 NNH remained stable across the different age classes. Instead for patients in CHADS2 score 4-6, NNH varied among the 3 groups of ages, reaching a value of 10 in patients >or=85 years.. Our data suggest that: 1) in AF patients older than 75 years with CHADS2 score 1-3 the risk of bleeding is low, 2) in AF patients >85 years with CHADS2 4-6 the risk of bleeding is high so that the use of OAT should be highly individualised.

Topics: Aged; Aged, 80 and over; Aging; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Risk Factors; Stroke; Warfarin

To study the recurrence of ischemic stroke in patient with nonvalvular atrial fibrillation (NVAF) and to determine the recurrence related factors of ischemic stroke in patients with NVAF.. The clinical data of 386 NVAF patients with ischemic stroke treated in our hospital from January 1992 to February 2002 were included in this study. The basic clinical information of each patient was recorded. Analysis of recurrence and recurrence related factors of ischemic stroke in patients with NVAF was conducted.. Overall the 10-year recurrence rate of ischemic stroke in patients with NVAF was 34%. Hypertension, diabetes mellitus, transient ischemic attack (TIA), hyperlipemia and mural thrombus in left atrium were significantly correlated with the recurrence rate by univariate Cox proportional hazards regression analysis; but aspirin therapy, warfarin therapy and hypertension control were protective factors for the recurrence of ischemic stroke in patients with NVAF. Multivariate Cox proportional hazards regression analysis revealed that hypertension, TIA and mural thrombus in left atrium were independent recurrence related factors for ischemic stroke in patients with NVAF; but aspirin therapy and warfarin therapy were protective factors for the recurrence.. Hypertension, TIA and mural thrombus in left atrium were independent recurrence related factors for ischemic stroke in patient with NVAF; but aspirin therapy and warfarin therapy were protective factors for the recurrence.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Multivariate Analysis; Recurrence; Regression Analysis; Retrospective Studies; Risk Factors; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Hospitalization; Humans; Insurance Claim Review; International Classification of Diseases; International Normalized Ratio; Ischemic Attack, Transient; Middle Aged; Patient Compliance; Rhode Island; Stroke; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Female; Humans; International Normalized Ratio; Interviews as Topic; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Stroke; Time Factors; Tomography, X-Ray Computed; Warfarin; Withholding Treatment

After a first cerebral ischemic event, secondary prevention should be started as soon as possible, especially in transient ischemic attacks where the risk of recurrence is the highest, especially during the first week, needing a diagnostic workup in a short period of time, secondary prevention measures depending on the presumed cause of the event. Secondary prevention of vascular events after transient ischemic attack or cerebral infarct consists of 3 types of strategies: 1. treatment of risk factors for stroke, especially high blood pressure, high cholesterol and smoking cessation; 2. aspirin (50 to 325 mg), or clopidogrel, or association aspirine-dipyridamole in high-risk subjects, or warfarin in patients with high-risk cardiopathies; and 3. carotid surgery in patients selected by clinical and imaging criteria. Other strategies are currently partly under evaluation: statins in normocholesterolemic ischemic stroke patients without coronary event, angioplasty with stenting. Audits of practice are necessary to determine whether patients are actually treated according to scientific evidence. This is a crucial issue if we want the results of trials to be translated in the true life, and really improve health at the community level.

Topics: Angioplasty, Balloon; Anticoagulants; Aspirin; Cerebral Infarction; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Humans; Hypolipidemic Agents; Ischemic Attack, Transient; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Recurrence; Risk Factors; Stents; Stroke; Ticlopidine; Time Factors; Warfarin

Topics: Anticoagulants; Aspirin; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Mortality; Stroke; Thromboembolism; Treatment Failure; Warfarin

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing.. To quantitate the influence of ethnicity on warfarin dose requirement.. We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age > or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for > or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin.. Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism.. Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

Topics: Aged; Asian People; Atrial Fibrillation; Black or African American; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hispanic or Latino; Humans; Hypothyroidism; International Normalized Ratio; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Stroke Volume; Venous Thrombosis; Ventricular Function, Left; Warfarin; White People

Topics: Anticoagulants; Cystathionine beta-Synthase; Factor V; Genetic Predisposition to Disease; Genetic Testing; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Methylenetetrahydrofolate Reductase (NADPH2); Platelet Activation; Platelet Aggregation; Polymorphism, Genetic; Prognosis; Protein S Deficiency; Prothrombin; Secondary Prevention; Stroke; Thrombophilia; Warfarin

To report a case of elevated international normalized ratio (INR) in a patient taking fish oil and warfarin.. A 67-year-old white woman had been taking warfarin for 1(1/2) years due to recurrent transient ischemic attacks. Her medical history included hypothyroidism, hyperlipidemia, osteopenia, hypertension, and coronary artery disease. She also experienced an inferior myocardial infarction in 1995 requiring angioplasty, surgical repair of her femoral artery in 1995, and hernia repair in 1996. This patient has her INR checked in the anticoagulation clinic and is followed monthly by the clinical pharmacist. Prior to the interaction, her INR was therapeutic for 5 months while she was taking warfarin 1.5 mg/d. The patient admitted to doubling her fish oil dose from 1000 to 2000 mg/d. Without dietary, lifestyle, or medication changes, the INR increased from 2.8 to 4.3 within 1 month. The INR decreased to 1.6 one week after subsequent fish oil reduction, necessitating a return to the original warfarin dosing regimen.. Fish oil supplementation could have provided additional anticoagulation with warfarin therapy. Fish oil, an omega-3 polyunsaturated fatty acid, consists of eicosapentaenoic acid and docosahexaenoic acid. This fatty acid may affect platelet aggregation and/or vitamin K-dependent coagulation factors. Omega-3 fatty acids may lower thromboxane A(2) supplies within the platelet as well as decrease factor VII levels. Although controversial, this case report illustrates that fish oil can provide additive anticoagulant effects when given with warfarin.. This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled. Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.

Topics: Aged; Drug Interactions; Fatty Acids, Omega-3; Female; Humans; International Normalized Ratio; Ischemic Attack, Transient; Self Medication; Warfarin

To report a case of possible interaction of smokeless tobacco with warfarin in a patient treated after several thromboembolic events.. A white man with a long history of smokeless tobacco use was unsuccessfully treated with warfarin up to 25-30 mg/day. International normalized ratio (INR) values never stabilized >2.0 over 4.5 years of therapy. This patient had experienced 3 myocardial infarctions (MIs) and 2 ischemic strokes between the ages of 29 and 31 years and experienced another MI at age 33 years. This was followed by several episodes of transient ischemic attacks at age 34 years. During the final year of warfarin treatment, tobacco use was terminated, followed by an increase in INR values from 1.1 to 2.3 within one week. Warfarin therapy was discontinued and smokeless tobacco use was reinstated and tapered slowly to discontinuation. Following warfarin discontinuation, ticlopidine therapy was initiated. Subsequently, this patient was placed on long-term clopidogrel therapy. Mechanisms responsible for this interaction have not been established, but would most likely involve an increased dietary source of vitamin K from tobacco.. Tobacco contains high levels of vitamin K, and its use may have contributed directly to the failure of warfarin therapy to achieve therapeutic INR levels in this patient. An objective causality scale indicates a probable association between this combination and the adverse effects. Smokeless tobacco use should be charted in patients undergoing warfarin therapy, and patients who desire to stop tobacco use should be aided in this process.. Possible health effects of smokeless tobacco may include potential drug interactions. These interactions may be based on pharmacodynamic and/or pharmacokinetic parameters involving any of the many pharmacologically active substituents of tobacco. Proposed mechanisms of drug interaction may include increased vitamin K levels in the diet.

Topics: Adult; Anticoagulants; Dose-Response Relationship, Drug; Drug Antagonism; Humans; International Normalized Ratio; Ischemic Attack, Transient; Male; Myocardial Infarction; Stroke; Thromboembolism; Tobacco, Smokeless; Treatment Failure; Warfarin

To report the occurrence of a transient ischemic attack (TIA) temporally related to the initiation of paroxetine.. A 57-year-old white man with a history of intermittent atrial fibrillation and hypercholesterolemia developed slurred speech and a facial droop 3 days after starting paroxetine. He was diagnosed with a TIA, hospitalized, and given anticoagulation treatment. The presenting symptoms resolved, but recurred when paroxetine was restarted 2 days later.. Platelets secrete serotonin, which mediates vasoconstriction through stimulation of 5-HT2a receptors. This is counterbalanced by the release of the vasodilator nitric oxide upon serotonin stimulation of endothelial 5-HT1 receptors. In conditions such as atherosclerosis, the damage to the endothelium leads to a greater vasoconstrictive response. Paroxetine has been reported to weakly inhibit norepinephrine reuptake and nitric oxide production in addition to increasing serotonergic activity, potentially compounding the vasoconstrictive response. An objective causality assessment revealed that the TIA was probably an adverse event resulting from use of paroxetine.. Use of paroxetine and other selective serotonin-reuptake inhibitors may result in changes of the vasculature and subsequent ischemic events in predisposed patients.

Topics: Anticoagulants; Drug Interactions; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Warfarin

Aside from anecdotal reports, there are few data on the risk of thrombotic complications in patients in whom use of warfarin and aspirin is discontinued perioperatively for cutaneous operation.. Our aim was to present a large case series of thrombotic complications resulting from this practice and to estimate the incidence of these events.. A total of 504 members of the American College of Mohs Micrographic Surgery and Cutaneous Oncology were surveyed regarding thrombotic complications when blood thinners were withheld perioperatively to ascertain the frequency of these complications and to describe associated morbidity and mortality.. A total of 168 responding physicians reported 46 patients who experienced thrombotic events. Of these patients, 54% (25 of 46) experienced the event when warfarin was withheld and 39% (18 of 46) when aspirin use was discontinued. Thrombotic events included 24 strokes, 3 cerebral emboli, 5 myocardial infarctions, 8 transient ischemic attacks, 3 deep venous thromboses, 2 pulmonary emboli, and 1 retinal artery occlusion leading to blindness. Three deaths were reported. Calculation of incidence yielded an estimated thrombotic risk of 1 event per 12,816 operations, 1 in 6219 operations when use of warfarin was discontinued and 1 in 21,448 when aspirin was withheld.. With no documented increase in severe hemorrhagic complications during continued use perioperatively of blood thinners, these data provide a compelling argument to maintain patients on medically necessary blood thinners during cutaneous operation. All relevant clinical facts must be weighed when making this decision.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mohs Surgery; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Complications; Stroke; Vascular Diseases; Warfarin

Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established.. Two hundred sixty-one adult patients (mean age 66 +/- 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 +/- 20.6 months).. LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P =.04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P =.0001). Survival free of TIA (Kaplan-Meier) was significantly less (P =.0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year (P <.0001), respectively.. To our knowledge, this is the first prospective study documenting an association between LA thrombus and TIA in patients with AF. Other TEE variables, including aortic atheromata, and clinical parameters were not independently predictive. These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Atria; Heart Diseases; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Regression Analysis; Risk Factors; Thrombosis; Warfarin

A 74-year-old woman with hypertension and bronchial asthma had chest discomfort at rest and 4 days later was admitted to her nearby hospital because of the sudden onset of right hemiparesis. The hemiparesis had almost disappeared within 24 h of onset, but because an electrocardiogram showed sinus tachycardia and diffuse symmetrical T-wave inversion, she was referred for cardiac examination. Coronary angiography did not reveal any significant coronary artery stenosis, but left ventriculography revealed severe hypokinesis of the left ventricular apical region, which contained a 4 x 4-mm solid thrombus moving freely with a wavy motion. Moreover, the activity of both protein C and protein S had decreased. The thrombus disappeared after 2 weeks of anticoagulant treatment with warfarin. Her clinical course suggested that the transient cerebral ischemic attack was caused by embolism of the left ventricular thrombus associated with 'tako-tsubo-like left ventricular dysfunction'.

Topics: Aged; Anticoagulants; Female; Heart Diseases; Heart Ventricles; Humans; Ischemic Attack, Transient; Radiography; Syndrome; Thrombosis; Ventricular Dysfunction, Left; Warfarin

To determine vascular risk factor (VRF) profiles in transient ischemic attack (TIA) and ischemic stroke.. We studied 239 patients with TIA and 1,473 ischemic stroke patients included in a prospective stroke registry over a 10-year period.. Main VRF were: hypertension, hyperlipidemia, diabetes mellitus and atrial fibrillation. In the multivariate analysis, prior ischemic stroke (OR=1.65; 95% CI, 1.07-2.56), atrial fibrillation (OR=1.60; 95% CI, 1.14-2.26) and current use of warfarin treatment (OR=0.34; 95% CI, 0.13-0.94) were the only independent risk factors associated with ischemic stroke.. Different potentially modifiable vascular risk factor profiles were identified in ischemic stroke versus TIA. This suggests that there are pathogenic differences between TIA and ischemic strokes.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain; Cerebral Infarction; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Ischemic Attack, Transient; Male; Multivariate Analysis; Predictive Value of Tests; Risk Factors; Surveys and Questionnaires; Warfarin

Medically refractory positional cerebral ischemia and concomitant orthostatic hypotension associated with chronic common carotid artery (CCA) occlusion are rare. The authors detail their experience with three cases treated exclusively by an extracranial bypass in which the thyrocervical trunk was used as the donor vessel. Postoperatively grafts were patent and symptoms resolved in all three patients, although orthostatic hypotension remained. Postural cerebral ischemia due to CCA occlusion can be treated by extracranial bypass surgery. The thyrocervical trunk is a suitable donor for reconstruction of the external carotid artery in these cases.

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, External; Cerebral Angiography; Cerebral Revascularization; Dizziness; Ephedrine; Fludrocortisone; Humans; Hypotension, Orthostatic; Ischemic Attack, Transient; Middle Aged; Paresis; Posture; Tomography, Emission-Computed, Single-Photon; Vision Disorders; Warfarin

Closure of patent foramen ovale (PFO) has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. We report our preliminary intermediate results of patients who underwent transcatheter PFO closure for paradoxical embolism using DAS-Angel Wings occluder or Amplatzer devices. Eighteen patients (8 male/10 female) underwent catheter closure of their PFOs at a median age of 42 years. The complete closure rate was 67% immediately after the procedure and 100% at a mean follow-up interval of 2.2 +/- 1.8 years. The mean fluoroscopy time and procedure time in the Amplatzer group were 8.5 +/- 3.2 min and 65 +/- 21 min, respectively, which were significantly shorter than those of DAS-Angel Wings group (18.9 +/- 4.7 min and 137 +/- 28 min, respectively). There were no recurrent embolic neurological events following device placement in this subset of patients. No complications were encountered either during or after the closure procedure. In conclusion, transcatheter closure of PFO seems to be an effective alternative therapy in the prevention of presumed paradoxical emboli. Further study is needed to identify patients most likely to benefit from this intervention.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aspirin; Catheters, Indwelling; Embolism, Paradoxical; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Risk Factors; Stroke; Treatment Outcome; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Comorbidity; Diabetes Complications; Double-Blind Method; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Isoindoles; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thromboembolism; Warfarin

The Maze procedure has proven to be extremely effective in curing medically refractory atrial fibrillation. This analysis of our surgical results with the Maze procedure indicates that the Maze procedure, with or without associated cardiac surgery, has the lowest perioperative stroke rate of any major cardiac surgical procedure. This is surprising in view of the fact that all of the patients who undergo the Maze procedure have an elevated risk of stroke because of the presence of atrial fibrillation. In addition, many of the patients have already had strokes, further increasing the likelihood of perioperative stroke. Only 1 patient has had a stroke in the 12-year follow-up period following the Maze procedure. This is comparable to the risk of stroke in the general population and indicates that the Maze procedure essentially abolishes the risk of stroke associated with atrial fibrillation.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiac Surgical Procedures; Female; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Survival Rate; Treatment Outcome; Warfarin

Topics: Aged; Anticoagulants; Aorta, Thoracic; Echocardiography, Transesophageal; Heparin; Humans; Ischemic Attack, Transient; Male; Thrombosis; Warfarin

To examine the use of warfarin in patients with atrial fibrillation (AF) admitted to hospital because of stroke or transient ischemic attack; and to describe the outcome of AF-associated stroke.. Review of the medical records of patients, identified from a prospective registry, admitted from January 1, 1994 through December 31, 1996.. Tertiary care teaching hospital.. AF was present in 92 of 722 (13%) patients at the time of admission. Only eight of 60 (13%) patients with ischemic stroke who were known to be in AF before their stroke were taking warfarin. The in-hospital case-fatality ratio for AF patients was more than double that of patients in sinus rhythm (21% versus 9%, respectively, P=0.001). AF patients were less likely to be discharged home (31% versus 59%, P=0.005). Of the 68 AF patients who survived, 74% left hospital taking warfarin. No warfarin-treated patient experienced intracranial bleeding while in hospital or during follow-up.. Patients with AF had more severe strokes than patients in sinus rhythm. A small proportion of patients with known AF were taking warfarin at the time of hospitalization. Bleeding complications were infrequent. Broader implementation of guidelines for the management of AF is justified to reduce the frequency of stroke in this group of patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Female; Hospital Mortality; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Registries; Stroke; Warfarin

Patients with intracranial vertebrobasilar artery (VBA) atherosclerotic occlusive disease have few therapeutic options. Unfortunately, VBA transient ischemic attacks (TIAs) herald a lethal or devastating event within 5 years in 25 to 30% of patients. The authors report their initial experience with eight patients in whom medically refractory TIAs secondary to intracranial posterior circulation atherosclerotic occlusive lesions were treated with stent-assisted angioplasty.. Eight patients (six men), ranging in age from 43 to 77 years, experienced signs and symptoms of VBA insufficiency despite combination therapy with warfarin and antiplatelet agents. Angiographic studies revealed severe distal vertebral (four patients), proximal basilar (one patient), or proximal and midbasilar stenoses (three patients). Aspirin and clopidogrel were administered for 3 days before primary angioplasty and stent placement, and this regimen was maintained by the patients on discharge. Patients underwent heparinization during the procedure and were given a bolus and 12-hour infusion of abciximab. A neurologist specializing in stroke evaluated all patients before and after the procedure. The VBAs in all patients were successfully revascularized with 7 to 28% residual stenosis. Six patients experienced no neurological complications. One patient died the evening of the procedure due to a massive subarachnoid hemorrhage. Two patients had groin hematomas, one developed congestive heart failure, and one had transient encephalopathy. All surviving patients are asymptomatic up to 8 months postoperatively.. Although primary intracranial VBA angioplasty with stent insertion is technically feasible, complications associated with the procedure can be life threatening. As experience is gained with this procedure, it may be offered routinely as an alternative therapy to patients with medically refractory posterior circulation occlusive disease that may develop into catastrophic VBA insufficiency.

Topics: Abciximab; Adult; Aged; Angiography; Angioplasty; Antibodies, Monoclonal; Anticoagulants; Aspirin; Basilar Artery; Cerebrovascular Circulation; Clopidogrel; Female; Follow-Up Studies; Heparin; Humans; Immunoglobulin Fab Fragments; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Premedication; Stents; Stroke; Subarachnoid Hemorrhage; Ticlopidine; Vertebral Artery; Vertebrobasilar Insufficiency; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Humans; Ischemic Attack, Transient; Risk Factors; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Hemorrhage; Humans; Ischemic Attack, Transient; Treatment Outcome; Warfarin

We report a patient with Noonan syndrome and asymptomatic cardiac disease (supravalvular aortic stenosis and pulmonary valvular stenosis) who had frequent transient ischemic attacks. Bilateral moyamoya was evident; in addition, he manifested activated protein C resistance and was heterozygous for the factor V Leiden mutation. Anticoagulation abolished his episodes and, despite extensive cerebrovascular disease, he has no permanent neurologic deficits. The association between Noonan syndrome and moyamoya has not previously been described. Disruption of vascular development in prenatal life may have resulted in both cardiac and cerebrovascular disease in this child.

Topics: Anticoagulants; Cerebral Angiography; Child; Drug Resistance; Humans; Ischemic Attack, Transient; Male; Moyamoya Disease; Noonan Syndrome; Protein C; Warfarin

To determine whether patients with nonvalvular atrial fibrillation (NVAF) have prothrombotic changes compared with patients in sinus rhythm.. Cross-sectional study. Hemostatic function compared in NVAF patients without prior embolic event (transient ischemic attack or embolic stroke) and control subjects without prior thrombotic stroke, and in NVAF patients with prior embolic event and control subjects with prior thrombotic stroke.. Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals.. A total of 75 NVAF patients (50 without and 25 with prior embolic event) and 42 control patients (31 without and 11 with prior thrombotic stroke) recruited concurrently over 18 months during 1990-91.. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and plasma levels of hemoglobin, fibrinogen, von Willebrand factor antigen, factor VIII, fibrin D-dimer, antithrombin III, protein C, protein S, fibrinopeptide A and prothrombin fragment F1+2. All statistical analyses were performed after adjustments for age and sex.. The NVAF patients without a prior embolic event had significantly higher mean hemoglobin and fibrinogen levels (p < 0.001 and p = 0.05, respectively) than the control subjects without prior thrombotic stroke. The 29 NVAF patients not taking warfarin (none had had an embolic event) had significantly lower mean protein C and protein S levels (p = 0.012 and p < 0.001, respectively) and a significantly higher fibrinopeptide A level (p = 0.03, after exclusion of outliers) than the control subjects without prior stroke. The NVAF patients with a prior embolic event had alterations in the hemostatic variables similar to those seen in the control patients with a prior thrombotic stroke. The latter had significantly higher fibrinogen, von Willebrand factor antigen and factor VIII levels (p = 0.04, 0.002 and 0.002, respectively) and significantly lower protein S levels (p = 0.02) than the control subjects without prior stroke.. NVAF patients without a history of an embolic event show evidence of a prothrombotic state compared with patients in sinus rhythm who have not had a thrombotic stroke. NVAF patients with a history of an embolic event show evidence of a prothrombotic state similar to that of patients in sinus rhythm who have had a thrombotic stroke. Prospective studies are needed to determine whether these abnormalities predict higher risk of stroke in individual NVAF patients.

Topics: Aged; Anticoagulants; Antithrombin III; Atrial Fibrillation; Cross-Sectional Studies; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Hemoglobins; Hemostasis; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Partial Thromboplastin Time; Peptide Fragments; Platelet Count; Protein C; Protein S; Prothrombin; Prothrombin Time; von Willebrand Factor; Warfarin

To determine whether plasma tissue plasminogen activator (tPA) levels (a) are higher in patients with novalvular atrial fibrillation (NVAF) than in control subjects in sinus rhythm; (b) differ between NVAF patients with and without a history of an embolic event (transient ischemic attack or embolic stroke); and (c) differ in control subjects with and without a history of thrombotic stroke.. Cross-sectional study.. Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals.. Seventy-four NVAF patients (24 with and 50 without a history of an embolic event), separated into 3 groups: no prior embolic event and no warfarin use (group 1), no prior embolic event and warfarin use (group 2), and prior embolic event and warfarin use (group 3). Forty control subjects in sinus rhythm (29 without and 11 with prior thrombotic stroke).. Plasma tPA levels.. The age-adjusted mean tPA levels exceeded the upper limit of normal in all 3 NVAF groups but not in the control groups. The NVAF patients had significantly higher mean tPA levels than the control subjects (p = 0.015). The levels did not differ significantly between the NVAF patients with a history of an embolic event and those without such a history. The control subjects with a history of thrombotic stroke had significantly higher mean tPA levels than the other control subjects (p = 0.03).. NVAF patients, regardless of their history of embolic events, and control patients with a history of thrombotic stroke have higher tPA levels than subjects in sinus rhythm without a history of stroke. A prospective, longitudinal study involving NVAF patients is required to determine whether high baseline tPA levels are associated with, and perhaps causally related to, an increased risk of stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Tissue Plasminogen Activator; Warfarin

Stroke from surgically inaccessible intracranial atherostenosis remains a formidable clinical challenge. While antithrombotic or antiplatelet therapy may prevent distal embolism, there is no effective program for plaque stabilization preventing progression of atherosclerotic stenosis. In patients with isolated circulations (single vertebral with absent posterior communicating arteries, single carotid with contralateral internal carotid artery occlusion, or single carotid with an absent anterior communicating artery), occlusion of the stenotic vessel may produce a low flow-mediated stroke. Fifteen patients with atherosclerotic intracranial stenoses were treated by balloon angioplasty after medical therapy with warfarin failed. Treated territories included the distal internal carotid, proximal middle cerebral, distal vertebral, and basilar arteries. Dilation was successful in all vessels, with residual stenoses averaging less than 30%. Two complications included one paramedian pontine stroke and a single vessel rupture that proved fatal. There was no recurrence of transient ischemic attacks and no restenosis at the angioplasty site over a follow-up period of more than 24 months. In this small series, balloon angioplasty of intracranial vessels provided a therapeutic option for secondary stroke prevention in highly selected patients. Further studies will be necessary to establish the efficacy and safety of endovascular treatment in larger series.

Topics: Adult; Aged; Angioplasty, Balloon; Anticoagulants; Arteriosclerosis; Basilar Artery; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebral Arteries; Cerebrovascular Disorders; Disease Progression; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Regional Blood Flow; Rupture; Vertebral Artery; Warfarin

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt ( > or = 20 microbubbles) and group 2 (n = 18) with a "small" degree of shunt ( > or = 3 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p = 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patient foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk of subsequent adverse neurologic events compared with patients with a small degree of shunt.

Topics: Anticoagulants; Brain Ischemia; Cerebrovascular Disorders; Cohort Studies; Contrast Media; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Injections, Intravenous; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Sodium Chloride; Warfarin

The annual incidence of ischemic stroke among patients with chronic non-valvular atrial fibrillation is about 4.5 percent. In five controlled trials, oral anticoagulant therapy with warfarin reduced the annual incidence of stroke by 68 percent to 1.4 percent. The effect of aspirin has not been unequivocally determined. Aspirin reduced the annual risk of stroke by 18 percent (n.s.) in one trial, and by 44 percent in another, though the two trials differed both in mean age of the patients and in aspirin doses. Direct comparison of warfarin and aspirin revealed no difference in efficacy. Advanced age, previous stroke or transient ischemic attack (TIA), hypertension and diabetes were all found to be risk factors for stroke in patients with atrial fibrillation. In patients under 65 years of age without risk factors, the annual risk of stroke was 1 percent. After TIA or minor stroke, warfarin reduced the annual risk of a second stroke from 12 percent to 4 percent. Aspirin had no such effect. The annual incidence of major bleeding episodes was 0.2-2.0 percent in the warfarin-treated subgroup, 0.2-1.5 percent in the aspirin subgroup and 0-1.6 percent in the placebo subgroup. Based on findings in the above mentioned trials, warfarin (INR 2.0-3.0) is recommended for stroke prevention in patients over 60 years of age with non-valvular atrial fibrillation. Trials are under way to ascertain whether conventional warfarin treatment can be replaced by less complicated and safer treatments in patients with chronic atrial fibrillation.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Controlled Clinical Trials as Topic; Diabetes Complications; Female; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

We sought to determine the frequency of spontaneous cerebrovascular events in adult patients with cyanotic congenital heart disease and to evaluate any contributing factors.. Cerebrovascular events are a serious complication of cyanotic congenital heart disease in infants and children but are said to be uncommon in adults.. Between 1988 and 1995, 162 patients with cyanotic congenital heart disease (mean age 37 years, range 19 to 70) were retrospectively evaluated for any well documented cerebrovascular events that occurred at > or = 18 years of age. Events related to procedures, endocarditis or brain abscess were excluded.. Twenty-two patients (13.6%) had 29 cerebrovascular events (1/100 patient-years). There was no significant difference between those with and without a cerebrovascular event in terms of age, smoking history, degree of erythrocytosis, ejection fraction or use of aspirin or warfarin (Coumadin). Patients who had a cerebrovascular event had a significantly increased tendency to develop hypertension, atrial fibrillation, microcytosis (mean corpuscular volume < 82) and history of phlebotomy (p < 0.05). Even when patients with hypertension or atrial fibrillation were excluded, there was an increased risk of cerebrovascular events associated with microcytosis (p < 0.01).. Adults with cyanotic congenital heart disease are at risk of having cerebrovascular events. This risk is increased in the presence of hypertension, atrial fibrillation, history of phlebotomy and microcytosis, the latter condition having the strongest significance (p < 0.005). This finding leads us to endorse a more conservative approach toward phlebotomy and a more aggressive approach toward treating microcytosis in adults with cyanotic congenital heart disease.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Heart Defects, Congenital; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Smoking; Warfarin

Transcranial Doppler sonography (TCD) has been used to detect microembolic signals in a variety of clinical situations. We studied the prevalence of TCD-detected microemboli in 38 acute stroke patients.. Consecutive patients with acute anterior circulation stroke were stratified into high-risk (group 1), medium-risk (group 2), and low-risk (group 3) groups based on their risk factors for cerebral embolism.. Microemboli were detected in 11% of patients. They were present in 17% of group 1, 10% of group 2, and 0% of group 3 patients. Emboli were present in patients with mechanical prosthetic valves, carotid stenosis (> 70%), and mitral valve strands with a patent foramen ovale. Patients with microemboli more frequently had a history of cerebral ischemia compared with patients without microemboli (P < .05). They also more frequently had recent (< 3 months) symptoms compared with patients without microemboli (P < .05). In patients with a cardiac source of embolization, the number of microemboli detected was directly proportional to the acuity of previous symptoms.. These data suggest that TCD-detected microemboli are associated with an increased prevalence of prior cerebrovascular ischemia. The presence of TCD-detected microemboli could be a risk factor for cerebrovascular ischemia.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Carotid Stenosis; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Heart Diseases; Heart Failure; Heart Septal Defects, Atrial; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Mitral Valve; Myocardial Infarction; Risk Factors; Thrombosis; Ultrasonography, Doppler, Transcranial; Warfarin

Topics: Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Blue Toe Syndrome; Cohort Studies; Embolism, Cholesterol; Heparin; Humans; Ischemic Attack, Transient; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Dementia, Vascular; Humans; Hypertension; Ischemic Attack, Transient; Risk Factors; Warfarin

This non-randomized study surveys the prophylactic treatment of 154 patients after transient ischemic attack or ischemic stroke in the carotid artery territory. Clinical presentation and etiologies were compared on the basis of the proposed prophylactic treatment. A surgical intervention or a long-lasting anticoagulation was restricted to only 30 patients (20%) due especially to the gravity of the ischemic cerebral lesions, general deterioration, and the advanced age of most of the patients. The purpose is to emphasize the "down-to-earth" situation in current medical care of non-selected patients as distinguished from the strictly selected patients of randomized studies. More importance should be done to open studies which better reflect the daily medical reality.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Carotid Stenosis; Cerebrovascular Disorders; Endarterectomy, Carotid; Female; Humans; Ischemic Attack, Transient; Long-Term Care; Male; Middle Aged; Patient Care Team; Platelet Aggregation Inhibitors; Primary Health Care; Prospective Studies; Warfarin

To determine whether anticoagulation practices have changed when heparin and warfarin are used to treat cerebrovascular disease, and to determine the dosage of aspirin used to treat carotid territory transient ischemic attacks (TIAs).. A 1987 study documented that neurologists and neurology house officers were using excessive amounts of heparin and warfarin. Recent studies have demonstrated the efficacy and safety of low-intensity anticoagulation for preventing strokes, but no data are available on how these findings have affected the treatment practices of clinicians.. Questionnaires were sent to neurology staff at 10 medical centers. The questions dealt with the use of heparin, warfarin, and aspirin in stroke/transient ischemic attack patients. The nonparametric Wilcoxon rank sum test was used for analyzing the responses.. Ninety-three physicians responded compared with 52 in the prior study. Most (56 of 92; 61%) did not use an IV heparin bolus. The mean partial thromboplastin time (PTT) was 55 seconds, which was significantly less than the mean PTT of 62 seconds (p = 0.006) in the prior study. The mean prothrombin time (PT) fell to 16.0 seconds (range, 12.5 to 20.0) compared with a mean of 19.9 seconds (range, 15.0 to 27.0; p < 0.001) in the earlier study. There was a significant fall in the mean PT ratio from 1.74 (range, 1.20 to 2.25) to 1.49 (range, 1.12 to 2.50; p < 0.001). Most respondents used 325 mg qd of aspirin for treating TIAs.. At the centers studied, neurologists and neurology house officers are using less intense anticoagulation when treating stroke patients now than in 1986. This concurs with recent studies demonstrating the efficacy and safety of low-intensity anticoagulation in some clinical settings. The use of 325 mg/d of aspirin is common, although the data supporting its efficacy compared with higher doses are unclear.

Topics: Anticoagulants; Aspirin; Carotid Artery Diseases; Cerebrovascular Disorders; Data Collection; Follow-Up Studies; Heparin; Humans; Ischemic Attack, Transient; Neurology; Practice Patterns, Physicians'; Surveys and Questionnaires; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Ischemic Attack, Transient; Myocardial Infarction; Recurrence; Risk Factors; Ticlopidine; Warfarin

Previous studies, mainly autopsy-based, suggest that the spectrum of stroke in cancer patients differs from that of the general population. These studies also suggest that cerebrovascular events frequently are a manifestation of hypercoagulability. However, no studies that address this question in the adult oncological population from a clinical perspective are available. We therefore assessed the clinical impact of cerebral ischemic events in cancer patients and attempted to determine whether their occurrence represents a manifestation of Trousseau's syndrome.. A computerized database that records all neurological admissions and consultations at a tertiary medical center was used to retrospectively identify all patients with cerebral ischemic events and cancer.. Thirty-three patients representing 3.5% of all stroke consultations and admissions seen at the University of Massachusetts Medical Center were identified during the period 1988 through 1992. Large-vessel atherosclerosis was the most frequent cause of stroke. Furthermore, although 30% were determined to have hypercoagulability as a cause using clinical criteria, in only one of nine patients in whom tests were done was sufficient evidence present to make a presumptive diagnosis of disseminated intravascular coagulation. Irrespective of therapy, recurrent cerebral ischemic events were noted in only 6% of patients during a follow-up period averaging greater than 9 months, a figure that is similar to that for the risk of repeated events in the noncancer population.. Recognizing the limitations of this retrospective study, it appears nonetheless that conventional stroke origins account for the majority of cerebral ischemic events in the adult cancer population. Although hypercoagulability is present to a greater extent than in the nononcological population, recurrent strokes seem to occur no more frequently than in the nononcological population, and antiplatelet agents seem sufficient therapy for most patients.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Blood Coagulation Disorders; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Cohort Studies; Female; Follow-Up Studies; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Neoplasms; Recurrence; Retrospective Studies; Thrombosis; Warfarin

To examine community practices.. Physician practice policies were surveyed using case vignettes in which evaluation for carotid endarterectomy or use of anticoagulation therapy was at issue. Virtually the same group was surveyed in 1988 and again in 1991, after publication of carotid endarterectomy trials in symptomatic patients.. Greater Metropolitan Minneapolis-St. Paul, Minnesota.. Community and academic neurologists in practice of general adult neurology.. Percentage of respondents who would recommend the management option in question for each vignette.. Ninety-eight percent favored evaluation for carotid endarterectomy in appropriately symptomatic "good risk" patients in 1988 before proof of efficacy became available. Proof increased the percentage (from 67% to 92%) favoring evaluation in older, sicker, symptomatic patients but not the percentage of those favoring evaluation of bruit patients (1988: 33%; 1991: 24%). In 1991, a lower percentage recommended warfarin therapy after noncardioembolic transient ischemic attack; this was especially apparent in the vertebrobasilar case (1988: 59%; 1991: 37%). Both years, nine of 10 neurologists recommended heparin therapy for progressing stroke, while half to three-fourths used it after partial stroke or transient ischemic attack. Almost all would use anticoagulants for secondary prophylaxis after suspected cardioembolic stroke.. The results reflect a treatment-oriented empirical approach in this community and document quick clinical application of scientific evidence when it became available.

Topics: Aged; Cerebrovascular Disorders; Endarterectomy, Carotid; Female; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Minnesota; Practice Patterns, Physicians'; Warfarin

Transesophageal echocardiography (TEE) improves the diagnostic accuracy of transthoracic echocardiography in the identification of potential cardiac sources of embolus. However, there are few studies of the impact of TEE on the medical management of patients with focal cerebral ischemia. The records of 52 consecutive, hospitalized patients undergoing both TEE and transthoracic echocardiography for suspected cardiac source of embolus were reviewed to determine the influence of TEE on the decision to anticoagulate patients. Of 52 patients, 39 had focal cerebral ischemia (transient ischemic attack, n = 9; acute cerebral infarction, n = 30). In 4 of these 39 patients (10%), the TEE results changed the management of anticoagulation. In 19 of 39 patients (49%), the TEE results helped confirm anticoagulation decisions, and in 16 (41%), the results had no effect on anticoagulation decisions, because of overriding clinical information. Ten of the latter 16 patients had TEE evidence for a possible source of an embolus, but were not anticoagulated; 5 of these were poor candidates for long-term anticoagulation, and the others had right-to-left shunting across a patent foramen ovale or an interatrial septal aneurysm. Clinical variables (atrial fibrillation, TEE findings and pre-TEE anticoagulation status) were considered as possible predictors of post-TEE anticoagulation status using logistic regression analysis; the strongest predictor of post-TEE anticoagulation status was pre-TEE anticoagulation status (p < 0.0005). Despite the selection of patients presumed to receive maximal benefit from TEE, this study suggests that TEE findings are not predictive of subsequent anticoagulation management. However, TEE is at least confirmatory of anticoagulation decisions in most cases.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cerebral Infarction; Decision Making; Diagnostic Imaging; Echocardiography; Echocardiography, Transesophageal; Female; Forecasting; Heart Diseases; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Middle Aged; Thrombosis; Warfarin

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.

Topics: Blood Coagulation; Cerebrovascular Disorders; Female; Fibrinopeptide A; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Middle Aged; Monitoring, Physiologic; Peptide Fragments; Prothrombin; Prothrombin Time; Radioimmunoassay; Thromboplastin; Warfarin

Episodic cerebro or retinovascular ischemic events without apparent cause occur in patients with cancer. We report a patient in remission from lymphoma whose multiple episodes of presumed ocular ischemia occurred in the setting of a circulating lupus anticoagulant. Symptoms resolved following therapy with Warfarin.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brain; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Hypertension; Ischemic Attack, Transient; Lupus Coagulation Inhibitor; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Middle Aged; Remission Induction; Scotoma; Vincristine; Vision, Monocular; Warfarin

Cervical internal carotid dissection is not rare. Doppler ultrasound screening of young patients presenting with stroke, identified 10 patients with reduced common and internal carotid blood flow without any evidence of atheroma. Eight, on angiography proved to have a dissection of the cervical internal carotid artery. All were managed conservatively. Seven received anticoagulant therapy, stopping any further neurological symptoms.

Topics: Adolescent; Adult; Aortic Dissection; Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Angiography; Cerebral Infarction; Echoencephalography; Female; Follow-Up Studies; Heparin; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Tomography, X-Ray Computed; Warfarin

During an 8-year period ending in 1988, 173 consecutive patients with a history of previous cerebrovascular accident underwent general anesthesia for surgery. Five patients (2.9%) had documented postoperative cerebrovascular accidents from 3 to 21 days (mean, 12.2 days) after surgery. The risk of postoperative cerebrovascular accident did not correlate with age, sex, history of multiple cerebrovascular accidents, poststroke transient ischemic attacks, American Society for Anesthesia physical status, aspirin use, coronary artery disease, peripheral vascular disease, intraoperative blood pressure, time since previous cerebrovascular accident, or cause of previous cerebrovascular accident. Postoperative stroke was more common in patients given preoperative heparin sodium. We conclude that the risk of perioperative stroke is low (2.9%) but not easily predicted and that the risk continues beyond the first week of convalescence. Unlike myocardial infarction, cerebral reinfarction risk does not seem to depend on time since previous infarct.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anesthesia, General; Aspirin; Cerebrovascular Disorders; Female; Heparin; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Surgical Procedures, Operative; Warfarin

Intravenous heparin is frequently used to treat thromboembolic disease, but the consequences of stopping heparin have not been studied systematically. To determine whether discontinuing heparin poses a clinical risk, we examined the charts of 378 patients treated with heparin for transient ischaemic attack (TIA), reversible ischaemic neurological deficit, or ischaemic stroke from October 1979 to June 1985. Clinical deterioration, or a new TIA or stroke was more likely (p = 0.01) during the 24 hours after heparin was stopped in patients not already on aspirin or warfarin (10/143, 7%) than in patients receiving aspirin or warfarin before heparin withdrawal (3/215, 1%). Stopping heparin in patients not receiving aspirin or warfarin appears to expose them to an increased risk for TIA, stroke, or clinical deterioration.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Drug Therapy, Combination; Female; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors; Warfarin

Topics: Carotid Artery Diseases; Carotid Artery, Internal; Echocardiography; Female; Heart Septal Defects, Atrial; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Middle Aged; Radiographic Image Enhancement; Warfarin

We report the clinical features and prognosis in nine patients with angiographically documented basilar artery stenosis of the middle and distal segments. Six patients had transient ischemic attacks (TIAs), and in two this was their only clinical manifestation. The TIAs in four patients included two or more of the following symptoms: dizziness, diplopia, perioral numbness, dysphagia, weakness, or loss of consciousness. Two other patients had isolated symptoms of transient dizziness and unilateral weakness. Seven patients had posterior circulation strokes, preceded by TIAs in four. Basilar artery occlusive disease can affect any segment of the artery. The short-term prognosis of middle and distal basilar artery stenosis was good especially when patients were treated with warfarin or platelet antiaggregants.

Topics: Aged; Arterial Occlusive Diseases; Basilar Artery; Cerebral Angiography; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Tomography, X-Ray Computed; Warfarin

We analyzed the clinical features of symptomatic posterior cerebral artery (PCA) stenosis in 6 patients selected from 15 patients with angiographically documented PCA atherostenosis occurring during a 7-year period. Transient ischemic attacks (TIAs) were the major presentation in 5 patients. A homonymous visual field defect was present in 2 patients. TIA symptoms were predominantly visual or sensory, or both. The most common visual symptom was difficulty seeing to one side. One patient saw flashing lights. Sensory spells were always paresthetic, usually involving the arm and hand and occasionally the face and leg. Three patients had visual and sensory spells together. Two patients with a visual field defect had calcarine infarcts found by computed tomography. All patients were treated with warfarin. During follow-up (4 months to 4 years), no patient had a new stroke in the PCA territory, and only one continued to have TIAs. PCA atherostenosis is rarer then PCA embolic occlusion. In contrast to those with PCA embolism, our patients with PCA atherostenosis had more TIAs and fewer infarcts. The clinical features of PCA stenosis--preponderance of visual and sensory TIAs--distinguish this vascular lesion from stenosis of the middle cerebral artery.

Topics: Aged; Cerebral Angiography; Constriction, Pathologic; Female; Follow-Up Studies; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Male; Middle Aged; Tomography, X-Ray Computed; Vision Disorders; Warfarin

Currently, pharmacologic intervention is directed toward preventing further spread of damage in the patient with cerebrovascular disease. Anti-platelet agents decrease platelet aggregation responses and anticoagulants decrease formation of the fibrin plug. In addition to the potential clinical benefits of these agents, risks must be considered. Patient education and compliance are major factors for consideration when assessing and monitoring treatment plans. Therefore, it is beneficial to the patient for health care teams to engage in multidisciplinary rounds which foster a consistent approach to treatment and allow each team member to make his unique contribution to the overall care of the patient.

Topics: Aspirin; Blood Platelets; Cerebrovascular Disorders; Dipyridamole; Drug Interactions; Heparin; Humans; Ischemic Attack, Transient; Monitoring, Physiologic; Risk; Warfarin

Topics: Anticoagulants; Bloodletting; Cerebral Infarction; Cerebrovascular Disorders; Fibrinolytic Agents; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Naloxone; Recurrence; Vasodilator Agents; Warfarin

In patients with transient ischemic attack (TIA), the risk of stroke increases greatly, especially in the months immediately following the initial attack. Diagnosis of TIA is based primarily on the patient's cerebrovascular history, since results of neurovascular examination are usually normal. TIA is often related to atherosclerotic arterial disease but can have numerous causes. Migraine, focal seizures, and other neurologic conditions can closely mimic TIA. Surgical and medical therapies help minimize the risk of stroke. The choice of therapy depends on the vascular territory of ischemia, the cause of the attack, the patient's medical and neurologic condition, the availability of a skilled surgeon, and other factors.

Topics: Aged; Aspirin; Cerebrovascular Disorders; Dipyridamole; Humans; Ischemic Attack, Transient; Middle Aged; Neurologic Examination; Risk; Warfarin

Topics: Aspirin; Brain Ischemia; Carotid Arteries; Dicumarol; Dipyridamole; Endarterectomy; Heart Murmurs; Heparin; Humans; Hypertension; Ischemic Attack, Transient; Risk; Sulfinpyrazone; Warfarin

Of 217 patients with clinical diagnosis of acute stroke 23% had nonischemic lesions diagnosed by computed tomography (CT) or lumbar puncture (LP). CT demonstrated all 37 cases of intracerebral hemorrhagic lesions; 9 were detected by LP. CT failed to demonstrate 8 of 17 cases of subarachnoid hemorrhage, but only 1 of these lacked headache or stiff neck. In 7 of 342 patients who were treated with anticoagulants after LP, spinal hematoma followed LP ( 5 with paraparesis). CT evaluation reduced the incidence of fatal cerebral hemorrhage during anticoagulant therapy of acute stroke. However, even if patients were evaluated with both CT and LP, the incidence of fatal cerebral hemorrhage resulting from intravenous anticoagulant therapy was 2.4%.

Topics: Anticoagulants; Cerebrovascular Disorders; Hematoma; Heparin; Humans; Ischemic Attack, Transient; Spinal Cord Diseases; Spinal Puncture; Tomography, X-Ray Computed; Warfarin

Seventy consecutive patients receiving warfarin as an anticoagulant were evaluated for the relationship between the response to the loading dose of warfarin and the response to the maintenance dose. No patients were excluded because of complicating diseases or the concurrent use of other drugs. There was a moderate correlation (r = 0.54, p less than 0.01) between response to the loading dose and response to the maintenance dose. Thus, a relatively weak response to a loading dose of warfarin can be used to predict a need for a relatively large maintenance dose in unselected patients requiring anticoagulant therapy. Age seems to be a relatively weak determinant of warfarin sensitivity. Other factors such as the genetic control mechanism, concurrent drug therapy, and complicating diseases apparently are more important determinants.

Topics: Adult; Aged; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Prothrombin Time; Pulmonary Embolism; Rheumatic Heart Disease; Thrombophlebitis; Warfarin

Eight patients with transient ischemic attacks, and three with partial nonprogressive strokes associated with mitral valve prolapse, are reported. No other etiology for their ischemic events was found. Only one episode of ischemia recurred on aspirin treatment, whereas none recurred on sodium warfarin therapy.

Topics: Adult; Aged; Aspirin; Carotid Artery Thrombosis; Cerebrovascular Disorders; Dipyridamole; Echocardiography; Electrocardiography; Female; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mitral Valve Prolapse; Recurrence; Warfarin

Topics: Aspirin; Humans; Ischemic Attack, Transient; Substance Withdrawal Syndrome; Warfarin

In 34 patients undergoing anticoagulant therapy with warfarin a close relationship has been observed between the logarithm of the 'Thrombotest' response to a loading dose (10 mg/day for three days) and the maintenance dose required to achieve an anticoagulant response of 8-12% (thrombo-test). This relationship appears to be close enough to enable maintenance dosages to be predicted.

Topics: Administration, Oral; Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Dose-Response Relationship, Drug; Female; Heart Valve Diseases; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mitral Valve; Thrombophlebitis; Thrombosis; Warfarin

Patients with transient ischemic attacks (TIAs) due to atherosclerosis were studied by aortocranial arteriography. Onset of TIAs was before age 55 in 24% and between 55 and 64 in 47%. Men exceeded women by two to one. Of 160 patients, 77 were treated medically and 82 surgically. Five died in the immediate postoperative period. In the survivors, mortality has been the same in the medically and surgically managed groups. For patients with multiple lesions, surgical reconstruction of the carotid arteries was associated with very high surgical risk. In the medically treated group, anticoagulant therapy reduced the frequency of TIAs, but did not appear to protect patients from stroke. Mortality was 23% at four years, 57% of deaths being attributable to myocardial infarction and 38% to stroke.

Topics: Adult; Aged; Arteriosclerosis; Cerebrovascular Disorders; Diabetes Complications; Endarterectomy; Female; Follow-Up Studies; Heart Diseases; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Prognosis; Prospective Studies; Radiography; Risk; Warfarin

Topics: Heparin; Humans; Injections, Subcutaneous; Ischemic Attack, Transient; Male; Middle Aged; Warfarin

Topics: Adult; Basilar Artery; Brain Stem; Cerebral Angiography; Cerebrovascular Disorders; Cervical Vertebrae; Chiropractic; Humans; Ischemic Attack, Transient; Male; Vertebral Artery; Warfarin

Topics: Heparin; Humans; Ischemic Attack, Transient; Warfarin

Topics: Amino Alcohols; Animals; Anticoagulants; Bicarbonates; Cerebrovascular Disorders; Dipyridamole; Ethylamines; Fibrinolysin; Heparin; Ischemic Attack, Transient; Papaverine; Phenols; Pyridines; Rabbits; Vasodilator Agents; Warfarin

Topics: Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Angiography; Cerebrovascular Disorders; Dextrans; Hematologic Diseases; Heparin; Humans; Infarction; Injections, Intravenous; Ischemic Attack, Transient; Papaverine; Subclavian Steal Syndrome; Vertebral Artery; Warfarin

Topics: Adult; Blood Platelet Disorders; Busulfan; Female; Hemorrhage; Humans; Hyperplasia; Ischemic Attack, Transient; Megakaryocytes; Thrombocytosis; Vision Disorders; Warfarin

Topics: Adult; Angiography; Ataxia; Carotid Arteries; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Subclavian Steal Syndrome; Vascular Diseases; Vertebral Artery; Vertigo; Warfarin