warfarin and Cerebrovascular-Disorders

Topics: Anticoagulants; Cerebrovascular Disorders; Drug Therapy, Combination; Humans; Intracranial Thrombosis; Platelet Aggregation Inhibitors; Warfarin

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Anticoagulants; Atherosclerosis; Blood Coagulation Disorders; Cerebrovascular Disorders; Coumarins; Humans; Indenes; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Stroke outcomes in patients with atrial fibrillation (AF) tend to be worse than those in patients without AF. The objective of this study was to evaluate whether the cost benefits of anticoagulation for stroke prevention in AF may currently be underestimated by existing economic models that do not distinguish between different stroke outcomes.. A literature review was conducted in 3 areas: (1) studies comparing stroke outcomes in AF and non-AF patients; (2) studies providing long-term cost of stroke estimates; and (3) studies modeling the cost-effectiveness of anticoagulation with a vitamin K antagonist (eg, warfarin) in AF patients.. There is considerable evidence that stroke in AF patients has a worse outcome than in patients without AF, including higher mortality, severity, and recurrence rates, and greater functional impairment and dependency. Estimates of the long-term cost of stroke of different severities were between US 24,991 dollars for a mild stroke over 5 years and US 142,251 dollars for a major ischemic stroke over a lifetime (2004 prices). The cost of a severe ischemic stroke may typically be 3-times that of mild stroke. However, cost-effectiveness models for anticoagulation in patients with AF have used average (not AF-specific) cost-of-stroke data, and most have used stroke severity distributions derived from clinical trials, which may differ from those in clinical practice.. Existing economic models underestimate the cost benefits of anticoagulation for stroke prevention because they do not adjust for poorer outcomes associated with cardioembolic strokes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Ischemia; MEDLINE; Middle Aged; Models, Theoretical; Multivariate Analysis; Quality-Adjusted Life Years; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

To systematically review evidence from clinical trials about the management of neurological manifestations of Antiphospholipid Syndrome (APS).. Articles reporting case-control, cohort and prospective studies and treatment trials of primary or secondary stroke prevention in patients with aPL were identified in an OVID literature search from 1966 to 2004, using the keywords: APS, aPL and cerebrovascular disease. Articles were evaluated according to the standard system for assessing medical evidence to answer the following questions: (1) What is the role of aPL and recurrent stroke risk in both primary and secondary APS populations? (2) What is the evidence to support specific treatment strategies for secondary prevention of aPL-associated stroke? (3) What is the evidence to support specific treatment strategies for primary prevention of aPL-associated stroke?. (1) aPL are a risk factor for incident stroke (Grade A, established as useful for the given condition in the specified population). (2) The evidence to support the role of aPL in recurrent stroke is conflicting and, therefore, inconclusive. (3) Warfarin at moderate-intensity doses is equally effective in preventing a recurrent thrombotic event as warfarin at high-intensity doses in patients with APS (Grade A evidence, established as useful for the given condition in the specified population). (4) Warfarin, at moderate-intensity doses is as effective as aspirin (at a dose of 325 mg/day) in preventing recurrent thrombotic events in patients who are aPL-positive at the time of an initial stroke (Grade B evidence, probably useful for the given condition in the given population). (5) Currently there are no data to support the use of any prophylactic therapy in patients with aPL and no clinical manifestations for the purposes of preventing an incident stroke.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Case-Control Studies; Cerebrovascular Disorders; Clinical Trials as Topic; Cohort Studies; Female; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Stroke; Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chemoprevention; Drug Combinations; Echocardiography, Transesophageal; Electric Countershock; Humans; Intracranial Embolism and Thrombosis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Warfarin

Atrial fibrillation, a common disorder that affects nearly one sixth of the population aged 75 years and older, is a major risk factor for stroke.. To review and evaluate the evidence supporting the use of warfarin and/or aspirin for stroke prevention in patients with atrial fibrillation.. Prospective, randomized trials of patients with atrial fibrillation evaluating either warfarin or aspirin or both, from MEDLINE from January 1, 1966, to February 23, 1999.. Five primary prevention placebo-controlled studies, which had been formally pooled, 1 study evaluating secondary prevention of stroke, 1 study comparing warfarin with aspirin, and 3 studies of warfarin in combination with aspirin were identified.. The risk of developing stroke is heterogeneous and increases with each decade above 65 years; history of high blood pressure, diabetes mellitus, previous transient ischemic attack, or stroke; poor ventricular function; and in women older than 75 years. For patients younger than 65 years, without risk factors, and not receiving antithrombotic therapy, the risk of stroke is 1%/y; those without risk factors between the ages of 65 and 75 years have a risk of 1.1%/y if taking warfarin and 1.4%/y if taking aspirin. For all other patients, stroke risk is reduced from an untreated rate of between 4.3%/y and more than 12%/y to a rate of 1.2%/y to 4%/y with warfarin use.. The protection afforded by warfarin is most pronounced in patients at the highest risk for stroke, while aspirin treatment seems adequate in low-risk populations.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Echocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Warfarin

Atrial fibrillation is the commonest sustained disorder of cardiac rhythm and is associated with increased risk of stroke and thromboembolic events. Warfarin (dose-adjusted to a target INR of 2.0-3.0) has been well established to reduce this risk of stroke by 68% (95% CI 50-79%), while aspirin provides a risk reduction of 21% (95% CI 0-38%). Nevertheless, warfarin confers a risk of bleeding and the inconvenience of regular monitoring checks, while aspirin seems effective only for certain low-risk subgroups. Thus there have been strenuous efforts to improve thromboprophylaxis in atrial fibrillation, by using low-intensity anticoagulation regimens, combination antiplatelet therapy and refinement of risk stratification strategies. Attempts at using a low-intensity, fixed-dose warfarin regimen have, however, been disappointing. For now, a strategy of risk stratification should be adopted to identify highest risk patients with atrial fibrillation who would benefit from anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Middle Aged; Thromboembolism; Warfarin

A recent analysis of the literature, published in the 19 May issue of the JAMA, once again demonstrates the efficacy of warfarin, and its superiority on aspirin, in preventing stroke in patients with atrial fibrillation, at least in subjects at highest risk. However, a feasibility study, published in the 15 May issue of the British Medical Journal, points to the difficulties of implementing guidelines from evidence-based medicine in general practice, essentially because of the reluctance of the physician and/or the patient when the constraints, risks and even advantages of antithrombotic treatment are taken into account.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Evidence-Based Medicine; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Warfarin

To characterize the efficacy and safety of anticoagulants and antiplatelet agents for prevention of stroke in patients with atrial fibrillation.. Randomized trials identified by using the search strategy developed by the Cochrane Collaboration Stroke Review Group.. All published randomized trials testing antithrombotic agents to prevent stroke in patients with atrial fibrillation.. Data on interventions, number of participants, duration of exposure and occurrence of all stroke (ischemic and hemorrhagic), major extracranial bleeding, and death were extracted independently by two investigators.. Sixteen trials included a total of 9874 participants (mean follow-up, 1.7 years). Adjusted-dose warfarin (six trials, 2900 participants) reduced stroke by 62% (95% CI, 48% to 72%); absolute risk reductions were 2.7% per year for primary prevention and 8.4% per year for secondary prevention. Major extracranial bleeding was increased by warfarin therapy (absolute risk increase, 0.3% per year). Aspirin (six trials, 3119 participants) reduced stroke by 22% (CI, 2% to 38%); absolute risk reductions were 1.5% per year for primary prevention and 2.5% per year for secondary prevention. Adjusted-dose warfarin (five trials, 2837 participants) was more efficacious than aspirin (relative risk reduction, 36% [CI, 14% to 52%]). Other randomized comparisons yielded inconclusive results.. Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more efficacious than aspirin. The benefit of antithrombotic therapy was not offset by the occurrence of major hemorrhage among participants in randomized trials. Judicious use of antithrombotic therapy, tailored according to the inherent risk for stroke, importantly reduces stroke in patients with atrial fibrillation.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Hemorrhage; Humans; Placebos; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Electrocardiography; Humans; 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

Topics: Acute Disease; Anticoagulants; Aspirin; Brain Ischemia; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Platelet Aggregation Inhibitors; Prognosis; Ticlopidine; Warfarin

Factors associated with an increased risk of thromboembolic events in patients with atrial fibrillation (AF) include increasing age, rheumatic heart disease, poor left ventricular function, previous myocardial infarction, hypertension and a past history of a thromboembolic event. Patients with AF should be considered for anticoagulation or antiplatelet therapy based on the patient's age, the presence of other risk factors for stroke and the risk of complications from anticoagulation. In general, patients with risk factors for stroke should receive warfarin anticoagulation, regardless of their age. In patients who are under age 65 and have no other risk factors for stroke, either aspirin therapy or no therapy at all is recommended. Aspirin or warfarin is recommended for use in patients between 65 and 75 years of age with no other risk factors, and warfarin is recommended for use in patients without risk factors who are older than 75 years of age.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Electric Countershock; Hemorrhage; Humans; Incidence; Middle Aged; Randomized Controlled Trials as Topic; Risk; Risk Factors; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Synergism; Drug Therapy, Combination; Humans; Patient Selection; Risk; Warfarin

Five randomized trials of warfarin stroke prophylaxis in atrial fibrillation have undergone meta-analyses by the Atrial Fibrillation Investigators (AFI) and by the British Columbia Office of Health Technology Assessment (BCOHTA), with differing conclusions. The AFI, using the original data, applied a consistent definition of 'major' bleeding (intracranial, hospitalization or transfusion of at least 2 U of blood) and found an excess of six major bleeding events. The BCOHTA used the definitions used in the studies, including "any medical intervention", and counted an excess of 21 'major' bleeding events. They then compared these with only the most severe one-third of the strokes. The BCOHTA were concerned that lack of blinding may have influenced the diagnosis of mild stroke, but the data do not suggest diagnostic bias. The risk reduction in the BCOHTA analysis of the most severe one-third of strokes was almost identical to that in the remaining strokes. The value of treatment is best assessed by comparing good with bad events of similar impact, and eliminating strokes from analysis does not eliminate them from patients. The BCOHTA analysis confirms the risk reduction demonstrated by the AFI.

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Female; Humans; Male; Risk Factors; Warfarin

One of the important recent advances in stroke prevention is the demonstration that warfarin can substantially reduce the risk for stroke in patients with atrial fibrillation (AF). On average, patients with AF have a stroke risk of 4.5% per year. Anticoagulation reduces this to around 1.5% per year, a 70% relative risk reduction. The presence of additional risk factors, such as a recent stroke or transient ischemic attack, hypertension (particularly systolic hypertension), congestive heart failure, or diabetes, greatly increases stroke risk. Patients with any of these risk factors have a stroke risk of 8% per year or more. In contrast, patients under age 75 with none of these risk factors have a low risk for stroke (around 1% per year) when treated with aspirin. This risk stratification may help in identifying which patients with AF benefit most from anticoagulation. Anticoagulation has also been shown to prevent stroke in patients with other cardioembolic sources, including acute anterior wall myocardial infarction (particularly with echocardiographic evidence of thrombus), prosthetic heart valves, and dilated cardiomyopathies.

Topics: Anticoagulants; Cerebrovascular Disorders; Humans; Randomized Controlled Trials as Topic; Warfarin

To review the risk and pathogenesis of stroke associated with nonvalvular atrial fibrillation (AF) and the efficacies and risks of stroke prevention strategies.. About 16% of ischemic strokes are associated with AF; AF is an independent risk factor for stroke.. Review of the literature, focusing on 13 randomized trials of antithrombotic therapy.. 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. AF patients with low (about 1% per year), moderate (about 3% per year), and high (about 6% per year) stroke risks have been identified, but the generalizability of risk stratification schemes to clinical practice has not been fully assessed. AF patients with prior stroke or transient ischemic attack, even if remote, are at highest risk (about 12% per year). Adjusted-dose warfarin (target International Normalized Ratio [INR] 2-3) is highly efficacious for preventing stroke in AF patients (about 70% risk reduction) and is safe for selected patients, if carefully monitored. Aspirin has a modest effect on reducing stroke (about 20% risk reduction). The numbers of AF patients that would need to be treated with warfarin instead of aspirin for 1 year to prevent one ischemic stroke are about 200, 70, and 20 for those with low, moderate and high risk, respectively.. Many patients with nonvalvular AF have substantial rates of ischemic stroke. Stratification of stroke risk identifies AF patients who benefit most and least from lifelong anticoagulation. 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. For AF patients considered to have a moderate risk of stroke, individual bleeding risk during anticoagulation and patient preference should particularly influence the choice of antithrombotic prophylaxis.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Female; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Vitamin K; Warfarin

Nonvalvular atrial fibrillation (AF) is the most common cardiac disorder causing stroke and systemic emboli. Recent clinical trials have clearly demonstrated the effects of antithrombotic treatment in preventing these devastating complications of AF. This review summarizes the salient findings of the first 5 published studies the Atrial Fibrillation, Aspirin, Anticoagulation Study (AFASAK) from Copenhagen, Denmark; the Boston Area Anticoagulation Trial for Atrial Fibrillation (BATAFF); the Canadian Atrial Fibrillation Anticoagulation study (CAFA); the Stroke Prevention in Non-rheumatic Atrial Fibrillation (SPINAF) study; and the Stroke Prevention in Atrial Fibrillation study (SPAF I) from the United States. These trials emphasize the unequivocal benefits of warfarin therapy compared with no treatment. SPAF II showed that aspirin is quite effective in younger patients (<75 years) who have no risk factors. The European Atrial Fibrillation Trial (EAFT) and SPAF III demonstrated that in older patients (>75 years) who had associated risk factors, warfarin therapy at the target international normalized ratio (INR) of 2-3, is the best treatment; however, a combination of low intensity fixed-dose warfarin and aspirin is ineffective. Thus, the guidelines recommended by the American College of Chest Physicians should be followed in treating patients with AF.

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Europe; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; United States; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Electric Countershock; Fibrinolytic Agents; Humans; Risk Factors; Warfarin

Low-molecular-weight heparins (LMWH) are a new group of parenteral anticoagulants. They represent a major clinical advance in anticoagulation since the identification of unfractionated heparin (UFH) in 1922 and the introduction of the synthetic coumarin derivative, warfarin, in 1948. Their predictable pharmacokinetics, increased bioavailability, and longer plasma half-life allow for once- or twice-daily dosing and eliminate the need for routine laboratory monitoring. This simplified administration stands to alter the clinical practice of anticoagulation. This review high-lights recent clinical trials and focuses on studies comparing LMWH with the other two major anticoagulants: UFH and coumadin.

Topics: Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Coronary Disease; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Venous Thrombosis; Warfarin

Nonvalvular atrial fibrillation is associated with an overall risk of stroke of 4.5% per year. Advancing age, prior stroke or transcient cerebral ischemia, diabetes and hypertension are known risk factors. Ischemic stroke in patients with atrial fibrillation are generally more severe than ischemic stroke in patients with sinus rhythm. Warfarin is effective for primary and secondary prevention of ischemic stroke, reducing the risk by 68%. The effect of aspirin is still controversial, reducing the risk by 18-44%. Recent clinical trials have investigated the effect of warfarin given at a very low intensity either alone or combined with aspirin. The results from the SPAF III study demonstrated that a combination of mini-intensity warfarin plus aspirin was insufficient for stroke prevention in atrial fibrillation. Other trials now indicate, that oral anticoagulation at INR-values below 2.0 is not effective for stroke prevention in these patients. It is recommended that patients at high risk of stroke are treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65 without other risk factors can be given aspirin 325 mg/day. The present clinical challenge is to ensure effective and safe oral anticoagulation to patients with atrial fibrillation at high risk of stroke.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Cerebrovascular Disorders; Hemorrhage; Humans; Risk Factors; Thromboembolism; 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

To review the clinical trials evaluating warfarin for primary stroke prophylaxis in nonvalvular atrial fibrillation (NVAF), to discuss the relative benefits and risks of warfarin versus aspirin therapy, and to review the clinical practice guidelines and identify potential barriers to their implementation in clinical practice.. A MEDLINE literature search was performed to identify clinical trials of antithrombotic therapy for NVAF, clinical practice guidelines, studies evaluating physician practices and attitudes, cost-effectiveness studies, and pertinent review articles. Key search terms included atrial fibrillation, stroke, antithrombotic, warfarin, aspirin, and cost-effectiveness.. Prospective, randomized clinical trials were selected for analysis. Clinical practice guidelines from recognized panels of experts were reviewed. Comprehensive review articles were selected.. NVAF is a common arrhythmia that is associated with a substantial risk for stroke. Seven prospective, randomized, clinical trials have conclusively demonstrated the efficacy of warfarin for stroke prevention. The greatest benefits are achieved in older patients and those with comorbidities that increase their risk for stroke. The potential benefits of preventing a devastating stroke, however, must be weighed against the potential for bleeding complications. Warfarin has been shown to be cost-effective in high-risk patients, provided the rate of complications is minimized. Nonetheless, many physicians remain hesitant to implement warfarin therapy in older, high-risk patients. The clinical data on aspirin are less consistent than those observed with warfarin. Aspirin appears to be most effective in younger individuals or those considered to be at low risk for stroke.. In patients with NVAF, the personal, social, and economic consequences of stroke are often devastating. Clinical trials have provided definitive proof that the risks of stroke can be significantly reduced through the use of appropriate antithrombotic therapy. Despite this evidence and the recommendations of a number of clinical practice guidelines, variations in care exist that continue to place patients at risk. Additional outcomes research is needed to evaluate the impact of the clinical trial findings and practice guidelines on clinical practice and to develop methods for overcoming barriers to implementation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cost-Benefit Analysis; Drug Costs; Female; Hemorrhage; Humans; Male; Practice Guidelines as Topic; Warfarin

To assess the outcomes associated with warfarin treatment of patients with chronic nonvalvular atrial fibrillation (CNVAF) for prevention of primary stroke.. MEDLINE was searched for literature published from 1987 to August 1996. Search terms used were 'atrial fibrillation' and 'anticoagulants'.. Five published randomized controlled trials concerning primary stroke prevention.. Data were pooled across trials to estimate the magnitude of the effect for each of nine reported end-points. The annual probability of occurrence of each outcome was calculated, including standard errors and Mantel-Haenszel significance tests with 95% CIs.. In view of the lack of blinded assessment and documented low inter-rater reliability of soft neurological end-points, the analysis was limited to the relatively objective end-points of major strokes, fatal strokes, major bleeding and fatal bleeding. Warfarin did not reduce the incidence of fatal strokes to a statistically significant extent, nor was incidence of fatal bleeding increased significantly. Warfarin reduced the absolute annual incidence of major strokes in patients with CNVAF by 0.89%, while at the same time it increased the absolute annual risk of major bleeding incidents by 1.8%. Though small, these differences were statistically significant.. On balance, the margin between expected benefit and harm for warfarin prophylaxis in patients with CNVAF is uncomfortably thin. These results and conclusions differ from those of a previously published meta-analysis of these same studies.

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Incidence; Outcome Assessment, Health Care; Research Design; Risk Factors; Warfarin

Atrial fibrillation is an extremely common arrhythmia that is associated with significant sequelae. Certain aspects of therapy, such as anticoagulation, are studied in well-constructed randomized trials. Other therapy, such as the maintenance of sinus rhythm with antiarrhythmic agents, is supported by limited evidence. This article reviews the epidemiology and medical treatment of this arrhythmia, addressing anticoagulation, ventricular rate control, and restoration and maintenance of sinus rhythm. Randomized trials in progress that attempt to answer important questions in the management of atrial fibrillation are also discussed.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Electric Countershock; Heart Conduction System; Hemodynamics; Humans; Morbidity; Warfarin

Topics: Aspirin; Cerebrovascular Disorders; Humans; Risk Factors; Warfarin

Antithrombotic prophylaxis with long term warfarin or aspirin reduces thromboembolic risk in atrial fibrillation. Identification, risk assessment, and regular review of all patients with atrial fibrillation should be routine in general and hospital practice. Risk stratification is easily performed on clinical grounds--echocardiography may refine it.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Fibrinolytic Agents; Humans; Risk Factors; Thromboembolism; Warfarin

Left atrial appendage obliteration was historically ineffective for the prevention of postoperative stroke in patients with rheumatic atrial fibrillation who underwent operative mitral valvotomy. It is, however, a routine part of modern "curative" operations for nonrheumatic atrial fibrillation, such as the maze and corridor procedures.. To assess the potential of left atrial appendage obliteration to prevent stroke in nonrheumatic atrial fibrillation patients, we reviewed previous reports that identified the etiology of atrial fibrillation and evaluated the presence and location of left atrial thrombus by transesophageal echocardiography, autopsy, or operation.. Twenty-three separate studies were reviewed, and 446 of 3,504 (13%) rheumatic atrial fibrillation patients, and 222 of 1,288 (17%) nonrheumatic atrial fibrillation patients had a documented left atrial thrombus. Anticoagulation status was variable and not controlled for. Thrombi were localized to, or were present in the left atrial appendage and extended into the left atrial cavity in 254 of 446 (57%) of patients with rheumatic atrial fibrillation. In contrast, 201 of 222 (91%) of nonrheumatic atrial fibrillation-related left atrial thrombi were isolated to, or originated in the left atrial appendage (p < 0.0001).. These data suggest that left atrial appendage obliteration is a strategy of potential value for stroke prophylaxis in nonrheumatic atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Heart Atria; Heart Diseases; Humans; Mitral Valve Stenosis; Postoperative Complications; Thrombosis; Warfarin

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Diabetes Complications; Digoxin; Diltiazem; Embolism; Humans; Hypertension; Thromboembolism; Verapamil; 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

There is a demonstrated statistical association between atrial fibrillation, rheumatic valvular disease, and embolic stroke. This article assesses the results of 6 major clinical trials (AFASAK, BAATAF, SPINAF, SPAF [parts I and II], CAFA and EAFTA--see text for trial names). Multivariate analysis revealed 4 independent clinical features that identified patients with atrial fibrillation at an increased risk for stroke: hypertension, increasing age, previous transient ischemic attack, and diabetes mellitus. Without anticoagulation therapy, patients with any of these risk factors had a 4% annual risk of stroke. Patients with cardiac disorders such as congestive heart failure and coronary artery disease have a stroke rate 3 times higher than patients without any risk factors; patients with atrial fibrillation but no concomitant risk factors or structural heart disease seemed to have little concomitant risk for stroke. Meta-analysis revealed a 64% reduction of risk for stroke in patients treated with warfarin, as compared with placebo. The value of warfarin therapy in patients > 75 years old is less clear because of a high risk of hemorrhagic complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

To review the evidence for antithrombotic therapy in patients with nonrheumatic atrial fibrillation.. Five primary prevention trials and one secondary prevention trial compare antithrombotic therapy with placebo or no treatment. Two trials also determine the efficacy and safety of acetylsalicylic acid.. Warfarin reduces the risk of stroke by 68%. The effect is consistent in all identifiable groups of patients with nonrheumatic atrial fibrillation, except patients at serious risk of hemorrhage. The absolute benefit of anticoagulants varies among patients because of markedly different inherent risk of stroke among patient subgroups.. Anticoagulant therapy should be considered for all patients with atrial fibrillation. Oral anticoagulant therapy is more effective than ASA in reducing the risk of stroke among patients with nonrheumatic atrial fibrillation.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Treatment Outcome; Warfarin

Anticoagulant therapy to halt or limit a potentially devastating stroke carries both risk and an unproven benefit. Two case reports highlight potential pitfalls. Antiplatelet agents are indicated for ischemia secondary to artery-to-artery embolism. Anticoagulation should be undertaken only when a demonstrated cardiac embolic source places a patient at ongoing risk of repeated embolic stroke. This article reviews rational approaches to anticoagulation for neurologic patients.

Topics: Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Family Practice; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Patient Selection; Practice Guidelines as Topic; Radiography; Risk Factors; Warfarin

In comparison with the incidence of cerebrovascular accident in the general population, atrial fibrillation increases the risk by a factor of five. Although age is without doubt the main risk factor for cerebrovascular accidents in patients with permanent of paroxysmal non-valvular atrial fibrillation, other independent risk factors have been identified: a previous history of hypertension, cerebrovascular accident, heart failure or diabetes. These factors enable identification of a population at risk in which oral anticoagulation may be recommended with an excellent efficacy/risk ratio. Six large scale randomised controlled multicenter trials of primary prevention have been published with a total of over 2,800 patients with non-valvular atrial fibrillation. The combined results of these trials show that treatment with vitamin K antagonist (INR 2-3) leads to a significant reduction in the risk of an ischaemic cerebrovascular accident of 64% (95% CI [51-74]; p < 0.001) and in the risk of death from all causes of 28% (95% CI [12-47]; p = 0.038) with a slight increase in the risk of cerebral haemorrhage (+ 2.7% NS). Although the benefits of aspirin therapy are not as impressive (reduction of the risk of an ischaemic cerebrovascular accident of 22%; 95% CI [0-39]; p = 0.053), this alternative may be proposed in patients under 75 years of age without the previously mentioned risk factors. The value of combined aspirin-oral anticoagulant therapy, especially in high risk patients, has not yet been established and is under evaluation.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Middle Aged; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Treatment Outcome; Vitamin K; Warfarin

Warfarin is recommended as primary prophylactic therapy for patients older than 60 years with non-valvular atrial fibrillation and for patients with additional risk factors for thromboembolism. Warfarin should also be given as secondary prophylaxis. Patients with contraindications to warfarin should be given aspirin. Anticoagulant therapy is recommended against progressive ischemic stroke and in cardiogenic cerebral embolism, although conclusive evidence of the benefit is lacking. In the case of transient ischemic attacks and minor stroke, antiplatelet therapy reduces the risk of subsequent stroke by approximately 25 percent. Antiplatelet therapy is probably indicated in cases of acute, stable ischemic stroke.

Topics: Aged; Anticoagulants; Cerebrovascular Disorders; Humans; Risk Factors; Thrombolytic Therapy; Warfarin

We describe the case of a 67-year-old patient, who had a stroke with subsequent right hemiparesis two years before coming under our observation. Afterwards he had no more pathological manifestation until he had sudden dyspnoea and marked cyanosis, following a prolonged immobilization due to intervention for slipped disc. Symptomatology regressed rapidly, and few hours later, the patient came under our observation in relatively fair conditions. Echocardiography evidenced moderate enlargement of right heart cavities; by subcostal view we visualized the presence of thrombotic material crossing the foramen ovale. Color Doppler showed moderate tricuspid regurgitation. Pulmonary artery systolic pressure was estimated about 55 mm Hg. The patient was immediately anticoagulated firstly by heparin, and secondly by warfarin, maintaining good clinical conditions. After a treatment of two more weeks he could be discharged with prescription of indefinite anticoagulation. Before discharge an echo examination showed the thrombus was no longer present. Pulmonary systolic pressure was estimated about 40 mm Hg. This is one of the rare cases of direct visualization of impending paradoxical embolus documented in the cardiologic literature.

Topics: Aged; Cerebrovascular Disorders; Drug Therapy, Combination; Echocardiography; Heart Septum; Heparin; Humans; Male; Mitral Valve Insufficiency; Pulmonary Embolism; Thromboembolism; Tricuspid Valve Insufficiency; 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

Nonvalvular atrial fibrillation is an increasingly common condition. It may cause disabling symptoms and is an important risk factor for stroke. The goals of treatment include the relief and prevention of rate- and rhythm-related symptoms and the prevention of stroke and systemic emboli. Three principal treatments should be considered: pharmacologic rate control, cardioversion and antiarrhythmic therapy to restore and maintain sinus rhythm, and prophylactic anticoagulation or antiplatelet therapy to reduce the risk of stroke. The risks and benefits of each of these therapies have been reviewed. Symptoms, if present, can often be managed safely with rate-directed therapy alone. Until issues regarding safety and long-term efficacy are resolved, cardioversion and antiarrhythmic therapy should be limited to those patients whose symptoms cannot otherwise be controlled. The benefits of warfarin anticoagulation for the primary and secondary prevention of stroke in nonvalvular atrial fibrillation have been demonstrated convincingly by several randomized clinical trials. These benefits must be weighed against the real risk of major hemorrhage. For patients at low risk of stroke, the use of aspirin may be an acceptable alternative to warfarin sodium therapy.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cerebrovascular Disorders; Electric Countershock; Heart Rate; Humans; Warfarin

Atrial fibrillation (AF) predisposes to stroke, particularly in patients with rheumatic heart disease, congestive heart failure, arterial hypertension, diabetes mellitus or uncontrolled thyrotoxicosis. In those with rheumatic heart disease it is usual to give warfarin to reduce the incidence of stroke, although there has been no randomised controlled trial on which to base this approach. Whether patients with non-rheumatic AF should be anticoagulated was unclear when we tackled this subject five years ago. This article reviews the evidence from recent randomised controlled trials and considers whether anticoagulation with warfarin, or antiplatelet therapy with aspirin, should now be routine for patients with non-rheumatic AF.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Randomized Controlled Trials as Topic; Risk Factors; 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

Three new studies help clarify important clinical issues regarding antithrombotic therapy for stroke prevention in patients with atrial fibrillation. The European Atrial Fibrillation Trial compared the efficacy of oral anticoagulation, aspirin, and placebo for stroke prevention in patients with atrial fibrillation with a recent stroke or transient ischemic attack. The results of the Stroke Prevention in Atrial Fibrillation II trial, which compared the efficacy of warfarin and aspirin, provide new information regarding the risk of intracranial hemorrhage in elderly patients with atrial fibrillation. Finally, an analysis of pooled data from the first five randomized trials identified clinical features that are predictive of stroke risk in individual patients with atrial fibrillation. These studies address unanswered questions regarding atrial fibrillation and stroke and have significant implications for patient management.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Risk Factors; Warfarin

Atrial fibrillation is associated with an increased risk of ischemic stroke. Data on individual patients were pooled from five recently completed randomized trials comparing warfarin (all studies) or aspirin (the Atrial Fibrillation, Aspirin, Anticoagulation Study and the Stroke Prevention in Atrial Fibrillation Study) with control in patients with atrial fibrillation. The purpose of the analysis was to (1) identify patient features predictive of a high or low risk of stroke, (2) assess the efficacy of antithrombotic therapy in major patient subgroups (eg, women), and (3) obtain the most precise estimate of the efficacy and risks of antithrombotic therapy in atrial fibrillation. For the warfarin-control comparison there were 1889 patient-years receiving warfarin and 1802 in the control group. For the aspirin-placebo comparison there were 1132 patient-years receiving aspirin and 1133 receiving placebo. The daily dose of aspirin was 75 mg in the Atrial Fibrillation, Aspirin, Anticoagulation Study and 325 mg in the Stroke Prevention in Atrial Fibrillation Study. To monitor warfarin dosage, three studies used prothrombin time ratios and two used international normalized ratios. The lowest target intensity was a prothrombin time ratio of 1.2 to 1.5 and the highest target intensity was an international normalized ratio of 2.8 to 4.2. The primary end points were ischemic stroke and major hemorrhage, as assessed by each study.. At the time of randomization the mean age was 69 years and the mean blood pressure was 142/82 mm Hg. Forty-six percent of the patients had a history of hypertension, 6% had a previous transient ischemic attack or stroke, and 14% had diabetes. Risk factors that predicted stroke on multivariate analyses in control patients were increasing age, history of hypertension, previous transient ischemic attack or stroke, and diabetes. Patients younger than 65 years who had none of the other predictive factors (15% of all patients) had an annual rate of stroke of 1.0%, 95% confidence interval (CI) 0.3% to 3.0%. The annual rate of stroke was 4.5% for the control group and 1.4% for the warfarin group (risk reduction, 68%; 95% CI, 50% to 79%). The efficacy of warfarin was consistent across all studies and subgroups of patients. In women, warfarin decreased the risk of stroke by 84% (95% CI, 55% to 95%) compared with 60% (95% CI, 35% to 76%) in men. The efficacy of aspirin was not as consistent. The risk reduction with 75 mg of aspirin in the Atrial Fibrillation, Aspirin, Anticoagulation Study was 18% (95% CI, 60% to 58%), and with 325 mg of aspirin in the Stroke Prevention in Atrial Fibrillation Study the risk reduction was 44% (95% CI, 7% to 66%). When both studies were combined the risk reduction was 36% (95% CI, 4% to 57%). The annual rate of major hemorrhage (intracranial bleeding or a bleed requiring hospitalization or 2 units of blood) was 1.0% for the control group, 1.0% for the aspirin group, and 1.3% for the warfarin group.. In these five randomized trials warfarin consistently decreased the risk of stroke in patients with atrial fibrillation (a 68% reduction in risk) with virtually no increase in the frequency of major bleeding. Patients with atrial fibrillation younger than 65 years without a history of hypertension, previous stroke or transient ischemic attack, or diabetes were at very low risk of stroke even when not treated. The efficacy of aspirin was less consistent. Further studies are needed to clarify the role of aspirin in atrial fibrillation.

Topics: Aged; Analysis of Variance; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Warfarin

Published and ongoing studies of drug therapy for preventing stroke in patients with nonrheumatic atrial fibrillation (AF) are discussed, and updated recommendations are provided. Stroke is the most common complication of nonrheumatic AF; there are more than 75,000 such strokes each year in North America. Nonrheumatic AF increases the risk of stroke almost sixfold. Emboli from clots that form in the left atrium because of ineffective atrial contraction and turbulent blood flow may cause most of these strokes. The results of six randomized trials of antithrombotic therapy in patients with nonrheumatic AF are now available. In almost all of these trials, warfarin therapy significantly reduced the risk of stroke. One trial showed that aspirin significantly reduced the risk of stroke, but another trial did not support that finding. Ongoing trials are addressing the efficacy and risks of aspirin plus low-dose warfarin and very low intensity anticoagulation. Overall, the data suggest that patients who are younger than 75 years of age and who lack risk factors can be adequately protected against stroke with aspirin. Patients younger than 75 years who have risk factors but no contraindications to warfarin should receive warfarin. Patients older than 75 years appear to benefit from anticoagulation therapy, but this benefit is offset by the higher risk of bleeding complications. Lone AF is best managed with aspirin. Warfarin is superior to aspirin as a secondary intervention in patients with a recent thromboembolic event. Strategies for preventing stroke in patients with nonrheumatic atrial fibrillation continue to be refined.

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors; Warfarin

Several recent randomized clinical trials of anticoagulation in atrial fibrillation have demonstrated significant reduction in stroke rates with a small incidence of bleeding complications. The objective of this study was to determine whether the recommendations resulting from these trials have been implemented into routine practice, and if the anticoagulation control, therapeutic efficacy, and low complication rates achieved in the trials have been matched in community practice.. We analyzed the anticoagulation practices and outcomes obtained for patients in atrial fibrillation at a large staff model health maintenance organization (HMO). We reviewed the medical records of all patients in atrial fibrillation as of April 1990. We compared demographic characteristics and clinical risk factors between HMO patients and those in the clinical trials. We also compared anticoagulation monitoring, adequacy of anticoagulation control, and clinical outcomes at the HMO with those achieved in the clinical trials.. Of 238 HMO patients in atrial fibrillation, 198 were without contraindications and therefore eligible for anticoagulation. Of these, 168 were offered anticoagulation (84.8%) and 156 were receiving anticoagulation therapy (78.8% of those eligible). The HMO patients had a greater prevalence of comorbidities than those in the clinical trials. The routine monitoring interval at the HMO was estimated at between 36.3 and 40.9 days (compared with 21 to 28 days reported in the clinical trials). The prothrombin time ratios at the HMO were in the target range on 50% of days compared with 68% of days in the clinical trials. The annual stroke and major bleeding rates in the HMO patients (1.3% and 0.6%, respectively) were not significantly different from the rates in the clinical trials (1.3% and 1.1%, respectively). The annual minor bleeding rate of 13.6% at the HMO was greater than the 7.8% to 8.4% rates in the two trials with better anticoagulation control (Boston Area Anticoagulation Trial for Atrial Fibrillation and Stroke Prevention in Atrial Fibrillation Study) but was not significantly different than the rates of 12.7% and 13.7% of the two trials with poorer anticoagulation control (Canadian Atrial Fibrillation Anticoagulation Study and Stroke Prevention in Nonrheumatic Atrial Fibrillation Study).. Anticoagulation practices in this community setting appear to be good in that a large majority of patients were receiving anticoagulation therapy, and there were few major adverse outcomes. However, this study illustrates two common problems in attempting to apply the results of randomized clinical trials to routine practice: (1) differences between community patient populations and those on which the conclusions of clinical trials are based, and (2) less successful application of therapeutic interventions in settings other than that of a controlled clinical trial. The greater prevalence of comorbidities in the HMO patient population appears to convey a greater overall risk of thromboembolism and bleeding complications than in the clinical trials. In addition, the suboptimal anticoagulation control achieved at the HMO may increase the risks and decrease the potential benefits compared with those achieved in the clinical trials. Thus, the efficacy demonstrated in the clinical trials of anticoagulation in atrial fibrillation may not be directly translated into effectiveness in practice.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Diabetes Mellitus; Female; Health Maintenance Organizations; Humans; Hypertension; Male; Practice Patterns, Physicians'; Prothrombin Time; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Warfarin

1. Atrial fibrillation is a common disorder in the elderly. 2. Atrial fibrillation increases the risk of stroke five times that of patients in sinus rhythm. 3. Warfarin reduces the risk of stroke by two-thirds in this population. Aspirin might reduce the risk of stroke but by a lesser amount. 4. In this sample, statewide use of Warfarin for primary prophylaxis in patients under 80 was 21% (95% C.I. 14-28%) and use of either Warfarin or aspirin was 42% (95% C.I. 34-50%). 5. Smaller hospitals and hospitals not in Central Arkansas use Warfarin less frequently than larger institutions for prophylaxis of stroke. Likewise, these hospitals are less likely to give any stroke prophylaxis to patients with this condition.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Middle Aged; Primary Prevention; Risk Factors; Societies, Medical; Warfarin

A resurgence of interest in atrial fibrillation has led to research in several avenues. Observations on the behavior of the atrium during atrial fibrillation demonstrate that electrical activity is not entirely random and that sinus node activity persists despite surrounding fibrillation. Anticoagulation therapy for chronic atrial fibrillation is now accepted as optimal treatment, but randomized trials have excluded the majority of patients screened and the risk-benefit ratio of therapy in the average patient therefore remains unclear. This is being addressed in comparative trials of warfarin and aspirin and in an analysis of risk factors for stroke derived from a major trial. Assessment of the efficacy of therapy for the control of ventricular rate in atrial fibrillation has underscored the slow action of digoxin and raised the issue of suboptimal dosing. With the recognition that improvement of exercise capacity following cardioversion may be postponed for weeks, several studies have evaluated serial changes in ventricular function and shown that in some patients sinus rhythm is associated with an improved ejection fraction. Transesophageal echocardiography is an area of intense interest for the identification of patients at high risk of thromboembolism following cardioversion, and the significance of left atrial spontaneous echo contrast as well as the left atrial appendage contractile function are being investigated. Finally, new methods of arrhythmia termination are being evaluated and developed, and surgical approaches to atrial fibrillation are being expanded and refined.

Topics: Animals; Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Electric Countershock; Electrocardiography; Heart Atria; Humans; Sinoatrial Node; Warfarin

Epidemiologic studies have shown that atrial fibrillation (AF) raises the risk of stroke approximately fivefold, and that because AF is so common among the stroke-prone elderly, it accounts for about 15% of all strokes. Five recently completed, randomized trials consistently found that the anticoagulant warfarin can prevent most of the additional stroke risk due to AF. This effect was seen at low doses. The trials have also demonstrated that warfarin therapy can be safe if careful patient selection and monitoring are implemented. Three of the trials provided inconsistent, and currently inconclusive evidence about the efficacy of aspirin. The trials have not settled the anticoagulation decision for all patients. Warfarin remains a demanding and risky therapy, which many patients and physicians do not find attractive. Future research should attempt to refine the risk of stroke, and of major hemorrhage during warfarin therapy among patients with AF, and should seek safer, less demanding, yet effective antithrombotic regimens.

Topics: Aged; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Warfarin

Atrial fibrillation (AF) is a risk factor for ischemic stroke. In randomized trials, AF raised the risk of stroke nearly sixfold, cumulating in a 35% risk over a lifetime. Anticoagulation with warfarin reduces the danger of ischemic stroke, but carries hemorrhagic risks, making this agent unsuitable for treating many patients. Platelet inhibitor therapy with aspirin was highly effective for patients younger than 75 years of age in one study, but the reason for lower efficacy in older individuals is perplexing. These trials support a thrombotic mechanism for most strokes in patients with AF, but leave physicians in a quandary as to selection of optimum prophylaxis. Secondary analysis of patients given placebo identified predictors of thromboembolism, including a history of hypertension, congestive heart failure, and prior stroke or transient ischemic attack, and echocardiographic findings of left ventricular dysfunction or left atrial enlargement. The absence of these risk factors selects a fairly large subgroup of AF patients at comparatively low risk of stroke, for whom the danger and inconvenience of chronic anticoagulation may not be warranted. It is becoming clear that specific clinical and echocardiographic features allow individualized antithrombotic approaches within the broad category of patients with AF, to enhance therapeutic benefit while minimizing hemorrhagic risk.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Humans; Randomized Controlled Trials as Topic; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Prospective Studies; Risk Factors; Warfarin

Aspirin in doses of 325 mg to 1,300 mg per day is the drug of choice for prophylactic therapy in cerebrovascular disease. Ticlopidine, a platelet antagonist, is available for use in patients who cannot tolerate aspirin or who have not had success with aspirin therapy. Although ticlopidine is more effective than aspirin in preventing stroke, its use may be somewhat limited due to cost and the uncommon but serious side effect of neutropenia. Low-dose warfarin remains the drug of choice for the prevention of cardioembolic stroke. The role of warfarin in ischemic cerebrovascular disease is unknown.

Topics: Aspirin; Cerebrovascular Disorders; Humans; 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

The roles of heparin and warfarin in reducing morbidity and mortality after acute myocardial infarction (AMI) are reviewed. Full-dose i.v. heparin, with or without thrombolytic therapy, is indicated for the prevention of reinfarction and thromboembolism after AMI. Heparin therapy consists of a bolus dose of 5,000-10,000 units, followed by a continuous infusion to maintain the activated partial thromboplastin time at 1.5-2.5 times the control value, and should be continued for 5-10 days in most patients. A longer course of heparin may be appropriate after non-Q-wave AMI. Patients being switched to warfarin should continue to receive heparin until a therapeutic International Normalized Ratio (INR) has been achieved. Warfarin is indicated for the prevention of thromboembolism in patients with anterior-wall AMI and should be given for three months in most cases. Longer-term warfarin therapy should be considered for patients with additional risk factors for thromboembolism. Patients with non-Q-wave infarction who are at high risk of reinfarction may also benefit from long-term warfarin therapy. Warfarin should be administered to maintain an INR of 2.0-3.0. Aspirin reduces mortality and reinfarction rates after AMI and should be given indefinitely to all patients who do not have contraindications. Some patients may benefit from the combination of aspirin and warfarin. Ongoing trials should more adequately define the safety and efficacy of heparin and warfarin, as well as aspirin, alone and in combination in post-AMI patients. New anti-thrombotic agents may also prove beneficial.

Topics: Aspirin; Cerebrovascular Disorders; Drug Therapy, Combination; Heparin; Humans; Injections, Intravenous; Myocardial Infarction; Thrombolytic Therapy; Warfarin

Topics: Aspirin; Cerebrovascular Disorders; Humans; Myocardial Infarction; Thrombosis; Warfarin

Several ongoing studies are evaluating the optimal management of patients with cerebrovascular disease. The Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin (CASANOVA) study has shown that carotid endarterectomy is not recommended for asymptomatic patients with less than 90% carotid stenosis. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgical Trial (ECST) have demonstrated that endarterectomy should be considered for patients who had recent carotid artery territory ischemic symptoms associated with angiographically defined stenosis of greater than 70%. These and other trials are expected to provide further data regarding management of cerebrovascular disease, including treatment of those patients with moderate (30 to 69%) carotid stenosis. Until that time, treatment decisions must be made on a case-to-case basis.

Topics: Adult; Aged; Angiography; Aspirin; Cerebrovascular Disorders; Endarterectomy; Evaluation Studies as Topic; Female; Geriatrics; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Thrombolytic Therapy; Tomography, X-Ray Computed; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Warfarin

The role of antithrombotic therapy in reducing thromboembolic complications in patients with chronic atrial fibrillation has been clarified by the results of four major randomized and placebo-controlled trials. Patients with rheumatic heart disease complicated by atrial fibrillation should receive long-term warfarin therapy to reduce the risk of stroke unless an absolute contraindication exists. Patients with nonrheumatic atrial fibrillation should also be treated with low-dose warfarin therapy, especially if high-risk features for thromboembolism exist. In patients who have contraindications to warfarin therapy and in young patients with lone atrial fibrillation or paroxysmal atrial fibrillation, therapy with 325 mg of aspirin a day is preferred. Ongoing trials directly comparing aspirin and warfarin will provide additional insight into the optimal role of these antithrombotic agents in patients with atrial fibrillation.

Topics: Acute Disease; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Electric Countershock; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Research Design; Rheumatic Heart Disease; Risk Factors; Warfarin

Cardiac disorders associated with cerebral embolism including cardiac surgery, myocardial infarction, endocarditis and non-valvular atrial fibrillation (NVAF) are reviewed along with methods to detect cardioembolic sources. Warfarin and aspirin are effective in the primary prevention of stroke in NVAF but the relative efficacy remains to be determined.

Topics: Cerebrovascular Disorders; Heart Diseases; Humans; Intracranial Embolism and Thrombosis; Postoperative Complications; Risk Factors; Warfarin

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Humans; Meta-Analysis as Topic; Research Design; Warfarin

There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Brain Ischemia; Cerebrovascular Disorders; Heparin; Humans; Intracranial Embolism and Thrombosis; Neurology; Warfarin

The long-term use of oral anticoagulants like warfarin in artery disease has long been controversial. Possible aims of treatment include the primary or secondary prevention of systemic embolism, preventing recurrence after myocardial infarction or the progression of transient cerebral ischemia to a complete stroke, and the prevention of artery graft occlusion. The value of long-term anticoagulation is generally accepted in the few situations where, as in patients with mechanical heart valve prostheses, mitral valve disease and atrial fibrillation, or idiopathic dilated cardiomyopathy, the risk of arterial thromboembolism without anticoagulation is known to be high and there is good evidence that anticoagulants are effective, so the benefit:risk balance strongly favours their use. In many settings, however, it is hard to justify long-term warfarin treatment as the benefit:risk balance remains unknown; either because the risk of thromboembolism without anticoagulation remains to be clearly defined (as in the case of patients with 'lone' atrial fibrillation), or because possible benefits have not been well documented (as after transient cerebral ischemia or peripheral vascular surgery). Finally, there is the difficult problem of estimating the benefit from long-term anticoagulation after myocardial infarction. It seems that warfarin can reduce the likelihood of non-fatal reinfarction with relative safety in highly selected patients, but whether it reduces mortality, and how its effect compares with that of other, more recent, therapies aimed at preventing reinfarction, remains unknown.

Topics: Cerebrovascular Disorders; Embolism; Humans; Myocardial Infarction; Vascular Diseases; Warfarin

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

Topics: Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Coronary Disease; Female; Fibrinolytic Agents; Heparin; Humans; Male; Myocardial Infarction; Phenindione; Pulmonary Embolism; Time Factors; United Kingdom; United States; United States Department of Veterans Affairs; 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

Topics: Adult; Angina Pectoris; Anticoagulants; Cerebrovascular Disorders; Coronary Disease; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vascular Diseases; Warfarin

Topics: Brain Ischemia; Cerebrovascular Disorders; Dicumarol; Ethyl Biscoumacetate; Geriatrics; Heparin; Phenindione; Warfarin

Topics: Acenocoumarol; Angina Pectoris; Anticoagulants; Cerebrovascular Disorders; Dicumarol; Heparin; Humans; Myocardial Infarction; Phlebitis; Rheumatic Heart Disease; Thromboembolism; Thrombophlebitis; Warfarin

To prospectively compare the efficacy and procedural safety of the radial versus femoral route for cardiac catheterization during uninterrupted warfarin therapy.. The optimal treatment strategy for cardiac catheterization in patients receiving long-term oral anticoagulation has not been defined. Increasing evidence suggests the feasibility and safety of catheterization without warfarin interruption. However, the relative safety and efficacy of the radial and femoral access in fully anticoagulated patients are unknown.. Fifty-six consecutive patients on chronic warfarin treatment with international normalized ratio (INR) between 1.8 and 3.5 were randomized to undergo coronary angiography, alone, or followed by percutaneous coronary intervention (PCI), via the femoral (n = 29) or radial route (n = 27). Procedural success, in-hospital major adverse cardiac and cerebrovascular events, access-site, and bleeding complications were recorded.. The two groups were well balanced with similar clinical characteristics at baseline. There were no significant differences in preprocedural antiplatelet therapy or in INR levels between the radial and femoral group (2.62 ± 0.7 vs. 2.48 ± 0.6, respectively, P = 0.63). Procedural success was achieved in all femoral patients, whereas one patient in the radial group (3.7%) required crossover to femoral access. Eight patients from the femoral and 10 patients from the radial group successfully underwent PCI. Access-site complications occurred only in patients who underwent PCI: three (37.5%) in the femoral versus none in the radial group (P = 0.034).. The radial access is as efficacious and safe as the femoral route for coronary angiography in fully anticoagulated patients, but is likely to result in fewer access-site complications in patients who also undergo PCI.

Topics: Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation; Cardiac Catheterization; Cerebrovascular Disorders; Chi-Square Distribution; Coronary Angiography; Female; Femoral Artery; Greece; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Prospective Studies; Radial Artery; Risk Assessment; Risk Factors; 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

There are limited data on the causes and severity of subsequent stroke in patients presenting initially with TIA or stroke attributed to intracranial arterial stenosis.. We evaluated the location, type (lacunar vs nonlacunar), cause, and severity of stroke in patients who had an ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial.. Of the 569 patients enrolled in the WASID trial, 106 patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years. Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106 patients. Among the 77 strokes in the territory, 70 (91%) were nonlacunar and 34 (44%) were disabling. Stroke out of the territory of the symptomatic artery occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were nonlacunar, 14 (48%) were attributed to previously asymptomatic intracranial stenosis, and 9 (31%) were disabling.. Most subsequent strokes in patients with symptomatic intracranial artery stenosis are in the same territory and nonlacunar, and nearly half of the strokes in the territory are disabling. The most commonly identified cause of stroke out of the territory was a previously asymptomatic intracranial stenosis. Penetrating artery disease was responsible for a low number of strokes.

Topics: Anticoagulants; Aspirin; Atherosclerosis; Brain Ischemia; Cerebral Arteries; Cerebrovascular Disorders; Constriction, Pathologic; Double-Blind Method; Embolism; Endpoint Determination; Humans; Platelet Aggregation Inhibitors; Recurrence; Stents; Stroke; Warfarin

atrial fibrillation (AF) is the commonest chronic arrhythmia with a prevalence of 9% in octogenarians and accounts for 24% of the stroke risk in this population. Although trials demonstrate reductions in stroke with warfarin, audit data show that it is still underused. However, anti-coagulation in the very elderly is not without risk.. randomised open labelled prospective study of primary thromboprophylaxis for AF. Patients aged >80 and <90 were randomised to receive dose-adjusted warfarin (INR 2.0-3.0) or aspirin 300 mg. All patients had permanent AF, were ambulant, had Folstein mini mental score >25 and had no contraindications to either treatment. Follow-up was for 1 year with 3 monthly visits. The primary outcome measure was a comparative frequency of combined endpoints comprising death, thromboembolism, serious bleeding and withdrawal from the study.. seventy-five patients (aspirin 39; warfarin 36) were entered (mean age 83.9, 47% male). There were significantly more adverse events with aspirin (13/39; 33%) than warfarin (2/36; 6%), P = 0.002. 10/13 aspirin adverse events were caused by side effects and serious bleeding; there were three deaths (two aspirin, one warfarin).. dose-adjusted warfarin was significantly better tolerated with fewer adverse events than aspirin 300 mg in this elderly population. Although aspirin 75 mg may have been better tolerated, there is no evidence for efficacy in AF at this dose.

Topics: Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Humans; Male; Platelet Aggregation Inhibitors; Warfarin

To investigate whether warfarin is more effective and superior to aspirin for the prevention of thromboembolism in nonvalvular atrial fibrillation in Chinese.. In a multicenter randomized trial, the patients diagnosed as nonvalvular atrial fibrillation were randomized to receive aspirin 150 mg - 160 mg once daily or adjusted-dose warfarin (international normalized ratio, 2.0 - 3.0). We compared the effect of the two therapy on the primary end point of ischemic stroke or death from any cause and on the combined end-point (stroke, death, peripheral arteries embolism, TIA, acute myocardial infarction, serious bleeding) during a median follow-up period of 19 months.. Of the 704 patients, 420 (59.7%) were male. The average patient age was (63.3 +/- 9.9) years. The median follow-up period is 19 months. The mean dose of warfarin was (3.2 +/- 0.7) mg. Compared with aspirin, the primary end point of death or ischemic stroke was reduced by warfarin (2.7% vs 6.0%, P = 0.03, OR 0.44, 95% CI 0.198 - 0.960) and the relative risk decreased by 56%. The thromboembolism event in the aspirin group was significantly higher than that in warfarin group (10.6% vs 5.4%, P = 0.01, OR 0.48, 95% CI 0.269 - 0.858). There was no significant differences of the mortality rate between the two groups (1.2% vs 2.2%, P > 0.05). The secondary end point was nonsignificantly reduced in warfarin group than that in aspirin group, while the combined end point is statistically decreased by adjusted-dose warfarin (8.4% vs 13.0%, P = 0.047). Warfarin treatment was associated with increased bleeding rate compared to aspirin (6.9% vs 2.4%, P < 0.05), although the major bleeding rate is rather low (1.5%). All the major bleeding events occurred with INR above 3.0.. Randomized control study demonstrated that anticoagulation with adjusted-dosed warfarin (INR 2.0 - 3.0) can significantly reduced the risk of thromboembolism event with slightly increased hemorrhage, compared to aspirin in Chinese population. Under intensive monitoring, warfarin is effective and safe for the moderate to high risk atrial fibrillation patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Warfarin

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Female; Humans; Male; Middle Aged; Multivariate Analysis; Primary Health Care; Scotland; Thromboembolism; Warfarin

Warfarin is effective in the treatment and prevention of many venous thromboembolic disorders, but it often leads to bleeding.. To develop a multicomponent program of management of warfarin therapy and to determine its effect on the frequency of warfarin-related major bleeding in older patients.. Randomized, controlled trial.. University hospital in Cleveland, Ohio.. 325 patients 65 years of age or older who started warfarin therapy during hospitalization.. Patients were stratified according to baseline risk for major bleeding and were randomly assigned to receive the intervention (n = 163) or usual care (n = 162) by their primary physicians for 6 months. The intervention consisted of patient education about warfarin, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of warfarin dosing.. Major bleeding, death, recurrent venous thromboembolism, and therapeutic control of anticoagulant therapy at 6 months.. In an intention-to-treat analysis, major bleeding was more common at 6 months in the usual care group than in the intervention group (cumulative incidence, 12% vs. 5.6%; P = 0.0498, log-rank test). The most frequent site of major bleeding in both groups was the gastrointestinal tract. Death and recurrent venous thromboembolism occurred with similar frequency in both groups at 6 months. Throughout 6 months, the proportion of total treatment time during which the international normalized ratio was within the therapeutic range was higher in the intervention group than in the usual care group (56% vs. 32%; P < 0.001). After 6 months, major bleeding occurred with similar frequencies in the intervention and usual care groups.. A multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients. Although the generalizability and cost-effectiveness of this program remain to be demonstrated, these findings support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin therapy in older patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Double-Blind Method; Drug Monitoring; Female; Hemorrhage; Humans; Male; Patient Care Planning; Patient Education as Topic; Prothrombin Time; Recurrence; Self Care; Venous Thrombosis; 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

Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin.. We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed.. Age (relative risk [RR]=1.8 per decade, P<0.001), female sex (RR=1.6, P=0.01), history of hypertension (RR=2.0, P<0.001), systolic blood pressure >160 mm Hg (RR=2.3, P<0.001), and prior stroke or transient ischemic attack (RR=2.9, P<0.001) were independently associated with increased stroke risk. Regular consumption of >/=14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4, P=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2, P=0.007). With the use of these variables, a risk stratification scheme for primary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants were less often disabling (P<0.001).. Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.

Topics: Aged; Alcohol Drinking; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Cohort Studies; Dose-Response Relationship, Drug; Drug Combinations; Estrogen Replacement Therapy; Female; Humans; Male; Multivariate Analysis; Regression Analysis; Risk Factors; Warfarin

Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients.. In the Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation (AFASAK 2) Study, we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; aspirin, 300 mg/d; or adjusted-dose warfarin therapy aiming at an international normalized ratio of the prothrombin time ratio (INR) of 2.0 to 3.0. The study was scheduled for 6 years from May 1, 1993, but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2, 1996. Minor and major bleeding events were recorded prospectively. The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model.. Of 677 included patients, 130 (median age, 77 years; range, 67-89 years) experienced bleeding. One woman and 12 men experienced major bleeding. Four had intracranial bleeding: 2 cases were fatal and 2 were nonfatal. During treatment with mini-dose warfarin, warfarin plus aspirin, aspirin, and adjusted-dose warfarin, the annual rate of major bleeding was 0.8%, 0.3%, 1.4%, and 1.1%, respectively (P = .20). After 3 years of treatment the cumulative rate of any bleeding was 24.7%, 24.4%, 30.0%, and 41.1% (P = .003), respectively. Increasing INRvalue (P<.001) and prior myocardial infarction (P = .001) were independent risk factors for bleeding, whereas increasing age was not.. Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding. The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy (INR, 2.0-3.0).

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Severity of Illness Index; Warfarin

Plasmin-alpha2-antiplasmin complex (PAP) is an index of recent fibrinolytic activity. We examined PAP levels in patients with atrial fibrillation (AF) to determine whether these levels are correlated with clinical characteristics associated with stroke risk. We obtained blood for measurement of PAP in a non-random sample of 586 patients with AF on entering the Stroke Prevention in Atrial Fibrillation III Study. PAP levels were measured with an ELISA assay. PAP values were transformed with a natural logarithm (PAPln) prior to all analyses. Older age, female gender, recent congestive heart failure, decreasing fractional shortening, recent onset of AF, and coronary artery disease were each univariately associated with higher levels of PAP (all p<0.05, two-sample t-test, simple linear regression). Older age, recent congestive heart failure, decreasing fractional shortening, and recent onset of AF were independently associated with higher PAP levels by multivariate analysis (linear regression). Among patients receiving warfarin, PAP levels were not correlated with INR levels (linear regression, p=0.60). Patients classified as high-risk for thromboembolism by our risk stratification criteria (systolic blood pressure > 160 mm Hg, prior thromboembolism, recent congestive heart failure, poor left ventricular function, and women over age 75) had higher PAP levels than low-risk patients (antilog mean PAPln 5.6 vs 4.9. p<0.001, two-sample t-test). PAP levels in patients with AF are associated with clinical characteristics predictive of thromboembolism. Elevated PAP levels are particularly associated with poor left ventricular function and are not affected by anticoagulation. PAP levels may be a marker of stroke risk in patients with AF.

Topics: Aged; alpha-2-Antiplasmin; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Cerebrovascular Disorders; Female; Fibrinolysin; Humans; Male; Middle Aged; Multivariate Analysis; Risk Factors; Warfarin

Decision aids are tools designed to help patients participate in the clinical decision-making process.. To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants.. Randomized controlled trial conducted from May 1997 to April 1998.. Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial.. A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years.. At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin.. Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured.. More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44).. For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Decision Making; Decision Support Techniques; Female; Fibrinolytic Agents; Humans; Logistic Models; Male; Patient Education as Topic; Patient Participation; Risk; Warfarin

Randomized trials have shown a beneficial effect of anticoagulation with warfarin to prevent stroke in atrial fibrillation. It is not known whether the same effect will be obtained in actual practice. The authors conducted a prospective observational study to evaluate the effect of preventive anticoagulation in patients with atrial fibrillation in 2 practice settings in Montreal.. Of the 1725 outpatients screened between October 1990 and September 1993 at a community hospital and a university-affiliated hospital, 221 with documented atrial fibrillation were enrolled and followed up for a mean of 27 months. Most (75%) of the patients excluded did not meet the inclusion criteria (because of, for example, an artificial heart valve, mitral stenosis, cardiac transplantation or transient atrial fibrillation); the remainder had not completed enrollment before the end of the study. Following the baseline visit, patients were interviewed by telephone every 6 months, and reported events were confirmed through review of the patients' charts. Hazards for stroke and for stroke and transient ischemic attack (TIA) combined were calculated for each of 4 treatment groups: ASA, warfarin, blended treatment and no treatment, based on the type of anticoagulation therapy patients received during the entire observation period. The blended-treatment group consisted of patients who started on one active therapy and switched to the other or who switched treatments more than once. Corresponding rate ratios (RRs) and 95% confidence intervals (CIs) were calculated with reference to the no-treatment group. Cox proportional hazards analysis was used to adjust for differences in patient characteristics. The rates of bleeding episodes were also analysed.. On average, the study patients were older (71.6 [standard deviation 9.3] years) and had a higher prevalence of underlying heart disease (52.0%) than those in the randomized trials. Nineteen patients had a first stroke: 4 in the ASA group, 4 in the warfarin group, 4 in the blended-treatment group and 7 in the no-treatment group, for rates of 5.2, 1.8, 5.3 and 5.9 per 100 person-years, respectively. Only warfarin was associated with a significantly lower risk of stroke compared with no anticoagulant therapy (RR 0.31, 95% CI 0.09-1.00). A similar protective effect of warfarin was found for stroke and TIA combined (2.3 v. 6.7 per 100 person-years; RR 0.34, 95% CI 0.12-0.99); the effect of ASA and blended treatment was not significantly different from no treatment. The rate per 100 person-years of any bleeding was not significantly higher for any treatment group (ASA 2.5, warfarin 3.4 and blended treatment 3.5) compared with the no-treatment group (1.9). Patients receiving warfarin had a significantly greater risk of any bleeding event than patients not receiving anticoagulant therapy (RR 1.79, 95% CI 1.07-3.00).. The relative effect of anticoagulant therapy with warfarin in preventing stroke in these practice settings was equivalent to that in the randomized trials, although these patients were older and sicker. This preventive treatment is likely to confer additional benefit as it is more widely prescribed.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Health Status; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Warfarin

We aimed to evaluate low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease (IHD).. 5499 men aged between 45 years and 69 years at high risk of IHD were recruited from 108 practices in the UK that belong to the Medical Research Council's General Practice Research Framework. Initially, warfarin or placebo was randomly allocated to 1427 men; 1013 of these men later moved to a factorial stage of the trial, retaining their warfarin or placebo warfarin allocation and adding randomly allocated active or placebo aspirin. Another 4072 men entered directly into the factorial stage making a total of 5085 men. The four factorial treatment groups were: active warfarin and active aspirin (WA, n = 1277), active warfarin and placebo aspirin (W, n = 1268), and placebo warfarin and active aspirin (A, n = 1268), and placebo warfarin and placebo aspirin (P, n = 1272). The primary end-point was all IHD defined as the sum of coronary death and fatal and non-fatal myocardial infarction (MI).. The mean International Normalised Ratio (INR) of those on active warfarin was 1.47. The mean warfarin dose was 4.1 mg a day (range 0.5 mg-12.5 mg). There were 410 IHD events (142 fatal, 268 non-fatal). The main effect of warfarin (i.e., WA and W vs A and P) was a reduction in all IHD of 21% (95% CI 4-35, p = 0.02) chiefly due to a 39% reduction (15-57, p = 0.003) in fatal events so that warfarin reduced the death rate from all causes by 17% (1-30, p = 0.04). The main effect of aspirin (i.e., WA and A vs W and P) was a reduction in all IHD of 20% (1-35, p = 0.04) almost entirely due to a 32% reduction (12-48, p = 0.004) in non-fatal events. Absolute reductions in all IHD due to warfarin or aspirin were 2.6 and 2.3 per 1000 person years, respectively. WA reduced all IHD by 34% (11-51, p = 0.006) compared with P. WA increased haemorrhagic and fatal strokes. Ruptured aortic or dissecting aneurysms occurred in 15 of those who were or had been on warfarin compared with three of those who had not (p = 0.01).. These results add to evidence that aspirin reduces non-fatal IHD. Warfarin reduced all IHD chiefly because of an effect on fatal events. Combined treatment with warfarin and aspirin is more effective in the reduction of IHD than either agent on its own.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Cerebrovascular Disorders; Double-Blind Method; Drug Therapy, Combination; Factor Analysis, Statistical; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Thrombosis; Warfarin

There are limited data on the prognosis of patients with angiographically proved symptomatic stenosis of the intracranial vertebral artery or basilar artery.. We studied 68 patients with 50% to 99% stenosis of one of the following arteries: intracranial vertebral (n = 31), basilar (n = 28), posterior cerebral (PCA) (n = 6), or posterior inferior cerebellar (PICA) (n = 3). All patients had previous transient ischemic attack or stroke in the territory of the stenotic artery and were treated with warfarin (n = 42) or aspirin (n = 26). Follow-up was by chart review and personal or telephone interview.. During a median follow-up of 13.8 months, 15 patients (22%) had an ischemic stroke (4 fatal), 3 patients (4.5%) had a fatal myocardial infarction (MI) or sudden death, and 6 patients (9%) had a nonfatal MI. Stroke rates in any vascular territory (per 100 patient-years of follow-up) were 15.0 in patients with basilar artery stenosis, 13.7 in patients with vertebral artery stenosis, and 6.0 in patients with PCA or PICA stenosis. Stroke rates in the same territory as the stenotic artery (per 100 patient-years of follow-up) were 10.7 in patients with basilar artery stenosis, 7.8 in patients with vertebral artery stenosis, and 6.0 in patients with PCA or PICA stenosis.. Patients with symptomatic intracranial vertebral artery or basilar stenosis are at high risk of stroke, MI, or sudden death. Further studies are needed to clarify optimal therapy for these patients.

Topics: Aged; Anticoagulants; Aspirin; Basilar Artery; Brain Ischemia; Cerebellum; Cerebral Arteries; Cerebrovascular Disorders; Constriction, Pathologic; Female; Humans; Male; Pilot Projects; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; Vertebral Artery; Warfarin

Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients.. The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996.. We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare.. Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Denmark; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Treatment Outcome; Warfarin

Five randomized trials of warfarin stroke prophylaxis in atrial fibrillation have undergone meta-analyses by the Atrial Fibrillation Investigators (AFI) and by the British Columbia Office of Health Technology Assessment (BCOHTA), with differing conclusions. The AFI, using the original data, applied a consistent definition of 'major' bleeding (intracranial, hospitalization or transfusion of at least 2 U of blood) and found an excess of six major bleeding events. The BCOHTA used the definitions used in the studies, including "any medical intervention", and counted an excess of 21 'major' bleeding events. They then compared these with only the most severe one-third of the strokes. The BCOHTA were concerned that lack of blinding may have influenced the diagnosis of mild stroke, but the data do not suggest diagnostic bias. The risk reduction in the BCOHTA analysis of the most severe one-third of strokes was almost identical to that in the remaining strokes. The value of treatment is best assessed by comparing good with bad events of similar impact, and eliminating strokes from analysis does not eliminate them from patients. The BCOHTA analysis confirms the risk reduction demonstrated by the AFI.

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Female; Humans; Male; Risk Factors; Warfarin

The prothrombin time (expressed as the international normalized ratio [INR]) is the standard method of monitoring warfarin therapy in patients with atrial fibrillation. Prothrombin activation fragment F1.2 provides an index of in vivo thrombin generation and might provide a better index of the effective intensity of anticoagulation. We examined the relationship between F1.2 and INR in patients with atrial fibrillation.. We measured INR and F1.2 levels in 846 patients with atrial fibrillation participating in the Stroke Prevention in Atrial Fibrillation III study. Two hundred nineteen (26%) were taking aspirin alone, 326 (39%) were taking adjusted-dose warfarin, and 301 (36%) were taking a low fixed dose of warfarin (1 to 3 mg) plus aspirin (combination therapy). F1.2 levels were measured with an enzyme-linked immunosorbent assay.. Patients receiving adjusted-dose warfarin or combination therapy had significantly higher INR and significantly lower F1.2 values than those on aspirin alone (P < or = .0001 for each of the four comparisons). F1.2 values (nanomolar) were inversely correlated with INR (F1.2 = -0.1 + 2.3[1/INR]; R2 = .37; P < .0001; simple linear regression). However, significant variability remained. Among patients receiving warfarin, older patients had higher F1.2 values than younger patients after adjustment for INR intensity (P < .001) in the model. There was no difference in the relationship between F1.2 and INR between men and women.. Increasing intensity of anticoagulation, as measured by the INR, is associated with decreasing thrombin generation as measured by the F1.2 level, but significant variability exists in this relationship. Older anticoagulated patients have higher F1.2 values than younger patients at equivalent INR values. The clinical significance of these differences is not clear. F1.2 measurement might provide information regarding anticoagulation intensity in addition to that reflected by the INR.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Coagulation; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Humans; Male; Peptide Fragments; Prothrombin; Prothrombin Time; Warfarin

The efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well-documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 + 2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1 + 2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1 + 2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in F1 + 2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1 + 2.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Prothrombin; Warfarin

The Stroke Prevention in Atrial Fibrillation II study compared the efficacy and safety of aspirin and warfarin in patients with atrial fibrillation. Three neurologists, blinded to patient therapy, categorized the pathophysiology of ischemic strokes that occurred in the trial based on predetermined clinical criteria. Upon analyzing the patients being treated with these two drugs, warfarin proved significantly more effective than aspirin in preventing cardioembolic strokes (p = 0.005) and strokes of uncertain pathophysiology (p = 0.01). There was no significant difference in the efficacy for prevention of noncardioembolic strokes.

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation. Bleeding complications importantly detracted from warfarin's net effectiveness, particularly among older patients.. To analyze bleeding complications according to assigned therapy. To identify risk factors for bleeding during anticoagulation.. Eleven hundred patients (mean age, 70 years) were randomized to 325 mg of aspirin daily (enteric coated) vs warfarin (target prothrombin time ratio, 1.3 to 1.8; approximate international normalized ratio, 2.0 to 4.5). Major hemorrhages were defined prospectively.. The rate of major bleeding while receiving warfarin was 2.3% per year (95% confidence interval [CI], 1.7 to 3.2) vs 1.1% per year (95% CI, 0.7 to 1.8) while receiving aspirin (relative risk, 2.1; 95% CI, 1.1 to 3.1; P = .02). Intracranial hemorrhage occurred at 0.9% per year (95% CI, 0.5 to 1.5) with warfarin and 0.3% per year (95% CI, 0.1 to 0.8) with aspirin (relative risk, 2.4; P = .08). Age (P = .006), increasing number of prescribed medications (P = .007), and intensity of anticoagulation (P = .02) were independent risks for bleeding at any site during anticoagulation. The rate of major hemorrhage was 1.7% per year in patients aged 75 years or younger who received anticoagulation vs 4.2% per year in older patients (relative risk, 2.6, P = .009); rates by age for intracranial bleeding were 0.6% per year and 1.8% per year, respectively (P = .05).. Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Risk Factors; Warfarin

To determine the effect of the results of clinical trials on the behaviour of patients and physicians, the authors ascertained the proportion of patients participating in the Canadian Atrial Fibrillation Anticoagulation (CAFA) study who started or continued warfarin therapy at the end of the study and identified factors affecting the decision to use or not use warfarin. The CAFA study was a double-blind, randomized, placebo-controlled, multicentre study to evaluate the efficacy of warfarin in preventing stroke among patients with nonrheumatic atrial fibrillation. Recruitment and follow-up were stopped early because two other similar studies had shown a decrease in the rate of stroke among patients treated with warfarin.. Mail survey 21 months after the end of the study.. The personal physicians of 336 patients who had participated in the CAFA study.. Type of antithrombotic therapy the patients had received since the CAFA study ended for patients who were not receiving warfarin, the reasons they were not.. Questionnaires concerning 254 (76%) of the patients who had participated in the study were returned. Since the end of the CAFA study, 153 (60%) of these patients had been treated continually with warfarin, 14 (6%) had been treated with warfarin but had subsequently stopped taking it, 59 (23%) had taken acetylsalicylic acid (ASA) continually, 5 (2%) had been taking ASA but had subsequently stopped taking it, and 23 (9%) had not taken either drug. The responding physicians stated that 58 (67%) of the patients who were not treated with warfarin did not wish to take the drug. The patients who had received warfarin during the CAFA trial were more likely to be treated with warfarin after the trial (75%) than were those who had received a placebo (56%) (p = 0.001). The probability of the patients' being treated with warfarin also depended on which study centre they had been treated in (p = 0.001).. Of the patients in the CAFA study for whom questionnaires were received, only 167 (66%) had been treated with warfarin after the end of the study. The patients were more likely to have been treated with warfarin after the study if they had received warfarin during the study. The positive results of clinical trials, on their own, are not enough to fully change the behaviour of patients and physicians.

Topics: Aged; Atrial Fibrillation; Cerebrovascular Disorders; Drug Utilization; Female; Follow-Up Studies; Humans; Male; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Risk Factors; Surveys and Questionnaires; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Peer Review; Treatment Outcome; Warfarin

Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism.. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled.. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups.. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Platelet Aggregation Inhibitors; Risk Factors; United States; Warfarin

Because most strokes cause neurological impairment rather than death, stroke prophylaxis may improve quality of life more than length of life. Thus, an understanding of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients.. We elicited quality-of-life estimates, known as utilities, for 3 degrees of severity of anticipated stroke-mild, moderate, and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy. We used the time tradeoff and standard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation.. Seventy patients completed the interview successfully. Their utilities for stroke ranged from worse than death (< 0) to as good as current health (1.0). The median utilities for mild, moderate, and major stroke were 0.94, 0.07, and 0.0, respectively. Although the median utilities decreased with increasing severity of stroke (P < .001), there was high interpatient variability within each degree of stroke severity. For example, 7 subjects (10%) rated a major stroke above 0.5, while 58 subjects (83%) rated it as equal to or worse than death. In contrast to the stroke utilities, the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0, respectively. However, the interpatient variability for warfarin therapy was also important: 11 patients (16%) with atrial fibrillation rated the utility of warfarin therapy so low that their quality-adjusted life expectancy would be greater with aspirin.. Patients' utilities for stroke prophylaxis and anticipated stroke vary substantially. Many patients view the quality of life with major stroke as tantamount to or worse than death. These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis.

Topics: Aged; Anticoagulants; Aspirin; Cerebrovascular Disorders; Female; Health Status; Humans; Male; Platelet Aggregation Inhibitors; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Warfarin

To determine the minimal clinically important difference (MCID) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods.. All patients completed 2 face-to-face interviews, which were 2 weeks apart. For each interview, they were randomized to receive 1 of 2 elicitation methods: ping-ponging or starting at the known efficacy.. The practices of 2 university-affiliated family medicine centers (8 physicians each), 14 community-based family physicians, and 2 cardiologists.. Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study.. During each interview, the patients' MCIDs were determined by using (1) a pictorial flip chart to describe atrial fibrillation; the consequences of a minor stroke, a major stroke, and a major bleeding episode; the chance of stroke if not taking warfarin; the chance of a major bleeding episode if taking warfarin; examples of the inconvenience, minor side effects, and costs of warfarin therapy; and then (2) 1 of the 2 elicitation methods to determine their MCIDs (the smallest reduction in stroke risk at which the patients were willing to take warfarin). Patients' knowledge of their stroke risk, acceptability of the interview process, and factors determining their preferences were also assessed.. Given a baseline risk of having a stroke in the next 2 years, if not taking warfarin, of 10 of 100, the mean MCID was 2.01 of 100 (95% confidence interval, 1.60-2.42). Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1% over 2 years. Before eliciting their MCIDs, patients showed poor knowledge of their stroke risk, which improved afterward. The interview process was well accepted by the patients. The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method (P = .01).. We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation. Their MCIDs were much smaller than those that have been implied by some experts and clinicians. The interview process, using the flip chart approach, appeared to improve the patients' knowledge of their disease and its consequences and treatment. The method used to elicit the patients' MCIDs can have a clinically important effect on patient responses. The method used in our study can be generalized to other conditions and, thus, could be helpful in 3 ways: (1) from a clinical decision-making perspective, it could facilitate patient-physician communication; (2) it could clarify the patient perspective when interpreting the results of previously completed trials; and (3) it could be used to derive more clinically relevant sample sizes for randomized treatment trials.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Middle Aged; Risk; Severity of Illness Index; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Risk Factors; 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: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Embolism; Female; Follow-Up Studies; Humans; Isoindoles; Italy; Male; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors; Risk Factors; Time Factors; Warfarin

We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspirin; Cerebral Angiography; Cerebral Hemorrhage; Cerebrovascular Disorders; Cohort Studies; Constriction, Pathologic; Female; Guinea Pigs; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Vascular Diseases; Warfarin

The comparative study of the efficacy of coumadin and aspirin in primary cardioembolic stroke prevention of chronic rheumatic heart disease (mitral stenosis) with atrial fibrillation was conducted at Siriraj Hospital, Mahidol University, Bangkok, Thailand. Seventy-nine patients were enrolled in the trial. Allocation of patients into coumadin or aspirin groups depended upon the patients' choice. Nineteen patients were given coumadin at the adjusted dosage to maintain the therapeutic range of International Normalised Ratio between 1.5-3. Sixty patients were given aspirin at the fixed dosage of 75 mg per day. Six patients were lost to follow-up over the 3 yr period; four in the aspirin group and 2 in the coumadin group. There were three patients with nonfatal cardioembolic stroke in the aspirin group but none in the coumadin group after three years of follow-up. Six patients had mitral valve replacement during the study (i.e. three patients in each group). There were complications in 12 patients, 10 in the aspirin (16.6 per cent) and 2 in the coumadin (10.5 per cent) group. The complications in coumadin group were minor bleeding over the thigh in one patient and generalised ecchymosis over the whole body in one other. In the aspirin group, the complication was gastrointestional symptoms, mainly epigastric pain, but no frank bleeding was observed. Primary prevention of cardioembolic stroke in chronic rheumatic heart disease was found to be more effective with coumadin than aspirin. Our study does not support the use of aspirin in primary prevention of cardiac embolism in chronic rheumatic heart disease.

Topics: Adolescent; Adult; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chi-Square Distribution; Chronic Disease; Female; Humans; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Survival Rate; Thromboembolism; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Isoindoles; Phenylbutyrates; Platelet Aggregation Inhibitors; Warfarin

Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation, but the value of this agent relative to aspirin in unclear. In the first Stroke Prevention in Atrial Fibrillation (SPAF-I) study, direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events. SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age. We compared warfarin (prothrombin time ratio 1.3-1.8, international normalised ratio 2.0-4.5) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism (primary events) in two parallel randomised trials involving 715 patients aged 75 years or less and 385 patients older than 75; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2% per year and 4% per year, respectively. In the younger patients, warfarin decreased the absolute rate of primary events by 0.7% per year (95% CI-0.4 to 1.7). The primary event rate per year was 1.3% with warfarin and 1.9% with aspirin (relative risk [RR] 0.67, p = 0.24). The absolute rate of primary events in low-risk younger patients (without hypertension, recent heart failure, or previous thromboembolism) on aspirin was 0.5% per year (95% CI 0.1 to 1.9). Among older patients, warfarin decreased the absolute rate of primary events by 1.2% per year (95% CI-1.7 to 4.1). The primary event rate per year was 3.6% with warfarin and 4.8% with aspirin (RR 0.73, p = 0.39). In this older group, the rate of all stroke with residual deficit (ischaemic or haemorrhagic) was 4.3% per year with aspirin and 4.6% per year with warfarin (RR 1.1). Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation, but the absolute reduction in stroke rate by warfarin is small. Younger patients without risk factors had a low rate of stroke when treated with aspirin. In older patients the rate of stroke (ischaemic and haemorrhagic) was substantial, irrespective of which agent was given. Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Follow-Up Studies; Humans; Risk Factors; Thromboembolism; Warfarin

The clinical effect of combined warfarin and antiplatelet therapy on the incidence of stroke and postoperative complications after mitral (plus aortic) valve replacement was studied and compared with that observed with warfarin therapy alone.. It has been reported that combined warfarin and antiplatelet therapy may be effective but may be associated with an increased hemorrhagic risk. Therefore, definite benefits of the treatment in patients with an implanted prosthetic valve have not been clearly documented.. Between January 1980 and December 1992, 195 patients with a St. Jude Medical valve at the mitral (plus aortic) position were assigned to receive treatment with either warfarin alone (125 patients) or warfarin plus antiplatelet agents (70 patients), such as dipyridamole (150 or 300 mg daily, 14 patients) or ticlopidine (200 or 400 mg daily, 56 patients). A minimal dose of aspirin (10 to 40 mg) was added (29 patients) if the maximal platelet aggregation rate by collagen was not reduced. The target thrombotest level was 10% to 20%.. The two treatment groups were similar with regard to gender and age distribution. The number of patients with atrial fibrillation, left atrial thrombus, history of previous stroke, simultaneous aortic valve operation and previously performed valve procedures were comparable in the two groups. Actuarial survival rate at 10 years was 98.3 +/- 1.7% (mean +/- SD) in the warfarin plus antiplatelet group and 90.3 +/- 3.2% in the warfarin group (p < 0.05 at 1 and 9 to 12 years). The actuarial stroke-free rate at 10 years was 95.3 +/- 3.4% and 84.3 +/- 3.8%, respectively (p < 0.05 by the generalized Wilcoxon test). The actuarial complication-free rate at 10 years was 89.4 +/- 4.3% and 67.9 +/- 4.8%, respectively (p < 0.05 by the generalized Wilcoxon test). No hemorrhagic complications were seen in the warfarin plus antiplatelet group.. The results strongly indicate the effectiveness and safety of combined warfarin plus antiplatelet treatment after St. Jude Medical valve replacement for mitral (plus aortic) valve disease.

Topics: Actuarial Analysis; Aortic Valve; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Stenosis; Platelet Aggregation Inhibitors; Postoperative Complications; Prosthesis Design; Warfarin

Non-valvular atrial fibrillation increases the risk of stroke by a factor of 5 and is present in about 15% of patients with acute stroke. Its prevalence in the general population increases from 0.5% at 50-59 years to > 10% at 80-99 years. In patients with non-valvular atrial fibrillation the risk of stroke increases with age, blood pressure and other evidence of cardiac disease. In addition, non-valvular atrial fibrillation is associated with a greater early mortality and a greater risk of recurrent stroke. The anticoagulant therapy to prevent early recurrent embolism is likewise controversial. Anticoagulant therapy appears to reduce this risk, but there is the danger of accentuating hemorrhagic infarction, especially in patients with large strokes. The effectiveness of antiplatelet drugs in patients with cardioembolic stroke is also not defined. The Studio Italiano Fibrillazione Atriale (SIFA) is a multicentric, randomized trial to assess the efficacy and safety of anticoagulant, warfarin, versus antiplatelet treatment, indobufen, a reversible inhibitor of platelet cyclo-oxygenase, in the prevention of recurrent cerebral ischemia and other systemic embolisms in non-valvular atrial fibrillation patients. Patients of both sexes, aged > 30 years with non-valvular atrial fibrillation, who have presented in the last 2 weeks an ischemic cerebral event (transitory ischemic attack or non-disabling stroke) and who have given their informed consent, were eligible. Patients with hemorrhagical diseases or contraindications to anticoagulant therapy were excluded. Patients were randomly given either indobufen (400 mg/die) or oral warfarin to an international normalized ratio of 2.0-3.5. The primary end-points were: recurrence of cerebral ischemia, systemic embolisms, intracranial or fatal hemorrhage, acute myocardial infarction, vascular death.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Isoindoles; Italy; Male; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors; Warfarin

The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization.. To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group).. The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1).. We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Hemostasis; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Peptide Fragments; Prothrombin; Warfarin

Although warfarin and perhaps aspirin may be effective in preventing thromboembolism in patients with nonvalvular atrial fibrillation, some patients develop cerebral infarction despite these therapies. The purpose of this study was to determine inhibition of platelet aggregation in patients on aspirin and platelet reactivity in those on warfarin in the Stroke Prevention in Atrial Fibrillation study.. Twenty-four patients in the Stroke Prevention in Atrial Fibrillation study at the University of Illinois at Chicago, 17 on enteric-coated aspirin 325 mg/d and 7 on warfarin to produce an International Normalized Ratio of 2.0 to 4.5, had platelet aggregation studies performed during a 10-month period and interpreted by an investigator blinded to therapy. Epinephrine, adenosine diphosphate, collagen, and arachidonic acid were used as aggregating agents. Compliance was determined by pill count for those patients on aspirin.. Seven patients taking aspirin had partial and 10 had complete inhibition of platelet aggregation. Three of seven patients on warfarin had hyperaggregable platelets. Compliance was 80% or greater for those patients taking aspirin. One patient on warfarin had partial inhibition of platelet aggregation.. Some patients in the Stroke Prevention in Atrial Fibrillation trial on aspirin 325 mg/d did not achieve complete inhibition of platelet aggregation. Others had hyperaggregable platelets. These findings suggest platelet-dependent mechanisms for aspirin and warfarin failure to prevent stroke in these patients.

Topics: Adenosine Diphosphate; Arachidonic Acid; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Collagen; Epinephrine; Humans; In Vitro Techniques; Kinetics; Platelet Aggregation; Warfarin

The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial.. The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II: Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL.kg-1 x min-1 in V-HeFT I and 13.7 mL.kg-1 x min-1 in V-HeFT II: Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p = 0.10 in V-HeFT I and p = 0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events.. The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified.

Topics: Cerebrovascular Disorders; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Hydralazine; Incidence; Isosorbide Dinitrate; Male; Middle Aged; Platelet Aggregation Inhibitors; Prazosin; Thromboembolism; Warfarin

High levels of fibrinogen and clotting factor VII are associated with an increased risk for subsequent death and cardiovascular disease in apparently healthy individuals. Furthermore, pathoanatomic studies and coronary angiography have confirmed a relationship between coronary thrombus formation and acute Q-wave infarction. Effective antithrombotic agents may prevent or limit thrombus formation and events related to thrombosis. The Warfarin Re-Infarction Study (WARIS) studied the effect of warfarin in survivors of acute myocardial infarction. Patients aged 75 years or less were randomized in a double-blind, placebo-controlled study to test whether long-term treatment with warfarin reduces the risk of death, reinfarction, and thromboembolic morbidity. A total of 1918 patients were screened for participation; 1214 were recruited. The mean follow-up was 37 months. Analyzed on an intention-to-treat basis, 123 (20%) in the placebo group died, versus 94 (15%) in the warfarin group, a risk reduction of 24% (P = 0.026). Considering patients on treatment or within 28 days after discontinuing the test medication, 92 in the placebo group died, as compared with 60 of the warfarin-treated patients, a risk reduction of 35% (P = 0.005). Relapsing myocardial infarction (fatal and nonfatal) was reduced by 43% (P = 0.0001). The incidence of cerebrovascular attacks was lower in the warfarin group (16 patients) than the placebo group (41 patients), a highly significant reduction of 61% (P = 0.0003). Serious bleeding occurred in 11 patients taking warfarin, an incidence of 0.6% per year. In conclusion, long-term anticoagulant therapy may be recommended after acute myocardial infarction.

Topics: Aged; Cerebrovascular Disorders; Double-Blind Method; Humans; Myocardial Infarction; Recurrence; Risk Factors; Survival Rate; Time Factors; Warfarin

Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk.. We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death.. Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history.. Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Topics: Aged; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Double-Blind Method; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Research Design; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Research Design; Warfarin

To assess the efficacy of immediate anticoagulation therapy on intracardiac thrombus formation in acute cardioembolic stroke, serial two-dimensional echocardiographic examinations were performed in 25 patients with acute cardioembolic stroke. Anticoagulation therapy was commenced within two days of onset in 7 patients (group A) but not in 18 patients (group B). Appearance or enlargement of intracardiac thrombi were not detected in group A but were noted in 7 patients (39%) of group B. Recurrence of systemic embolism was demonstrated in 3 patients (17%) of group B. There were no serious hemorrhagic complications in either group. Immediate anticoagulation could, therefore, be effective in preventing intracardiac thrombus formation and the consequent recurrence of systemic embolization in acute cardioembolic stroke. Because the study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anticoagulation therapy.

Topics: Cerebrovascular Disorders; Echocardiography; Female; Heart Diseases; Heparin; Humans; Male; Middle Aged; Recurrence; Thrombosis; Time Factors; Warfarin

Recent randomized trials have consistently demonstrated the marked efficacy of warfarin in reducing the risk of stroke caused by nonrheumatic atrial fibrillation. These trials have provided conflicting evidence on the effect of aspirin. We report the aspirin analysis from the BAATAF study, a trial in which control patients could choose to take aspirin. There we two strokes in 446 person-years with warfarin (annual rate of 0.45%); eight strokes in 206 person-years with aspirin, most at 325 mg per day (annual rate of 3.9%); and five strokes in 271 person-years among patients taking neither aspirin nor warfarin (annual rate of 1.8%). Simultaneously controlling for the other significant determinants of stroke in the BAATAF study (age, mitral annular calcification, and clinical heart disease), the relative rates (95% confidence interval) of stroke were: (1) warfarin/aspirin = 0.135 (0.029 to 0.64); (2) aspirin/(no aspirin and no warfarin) = 1.95 (0.64 to 5.97); and (3) warfarin/(no aspirin and no warfarin) = 0.263 (0.051 to 1.36). Our "treatment received" analysis argues that warfarin is strikingly more effective than aspirin in preventing stroke in nonrheumatic atrial fibrillation.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome; Warfarin

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Humans; Meta-Analysis as Topic; Research Design; Warfarin

The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Fibrillation; Canada; Cerebrovascular Disorders; Double-Blind Method; Female; Humans; Male; Risk Factors; Statistics as Topic; Thromboembolism; Warfarin

Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.. The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.. Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Warfarin

To determine the effect of long-term warfarin sodium therapy on quality of life, we surveyed 333 patients participating in a randomized, controlled trial of warfarin for the prevention of stroke in nonrheumatic atrial fibrillation. No significant differences between warfarin-treated and control patients were found on well-validated measures of functional status, well-being, and health perceptions. For example, the summary score for health perceptions was 68.8 in the warfarin-treated vs 66.6 in the control group (scale of 0 to 100; 95% confidence intervals for the difference, -1.6 to 6.0). In contrast, patients taking warfarin who had a bleeding episode had a significant decrease in health perceptions (-11.9; 95% confidence interval, -4.1 to -19.6). Warfarin therapy is not usually associated with a significant decrease in perceived health, unless a bleeding episode has occurred. Negative effects of warfarin treatment on health perceptions may be balanced by confidence in its protective effects.

Topics: Aged; Atrial Fibrillation; Attitude to Health; Cerebrovascular Disorders; Cross-Sectional Studies; Female; Follow-Up Studies; Health Status; Hemorrhage; Humans; Male; Prospective Studies; Quality of Life; Surveys and Questionnaires; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

Topics: Cardiomyopathy, Dilated; Cerebrovascular Disorders; Echocardiography, Doppler; Humans; Randomized Controlled Trials as Topic; Warfarin

Individuals with nonvalvular atrial fibrillation are at increased risk of stroke. The Stroke Prevention in Atrial Fibrillation Study is a 15-center randomized clinical trial examining the risks and benefits of low-intensity warfarin (prothrombin time of 1.3-1.8 times control) and aspirin (325 mg/day) in patients with constant or intermittent atrial fibrillation. Candidates for anticoagulation (group I) are randomized to receive warfarin in an open-label fashion, aspirin, or placebo; the last two treatments are given in a double-blind fashion. Warfarin-ineligible patients (group II) are randomized to receive aspirin or placebo in a double-blind fashion. Primary end points are ischemic stroke and systemic embolism. Secondary end points are death, transient ischemic attack, myocardial infarction, and unstable angina pectoris. Analysis is based on the intention-to-treat principle. The anticipated rate of primary end points in patients receiving placebo is 6%/yr. The sample size of 1,644 patients is based on a projected reduction in the rate of primary end points of 50% by warfarin and of 33% by aspirin (beta = 0.2, alpha = 0.05). Patient entry commenced in June 1987 and will continue for 3 years, with an additional year of follow-up. High-risk subsamples identified by clinical and echocardiographic criteria are sought prospectively.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Research Design; Statistics as Topic; Warfarin

The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infarction has been highly controversial. We therefore randomly assigned 1214 patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) to treatment with warfarin (607 patients) or placebo (607 patients) for an average of 37 months (range, 24 to 63).. At the end of the treatment period, there had been 123 deaths in the placebo group and 94 in the warfarin group--a reduction in risk of 24 percent (95 percent confidence interval, 4 to 44 percent; P = 0.027). A total of 124 patients in the placebo group had reinfarctions, as compared with 82 in the warfarin group--a reduction of 34 percent (95 percent confidence interval, 19 to 54 percent; P = 0.0007). Furthermore, we observed a reduction of 55 percent (95 percent confidence interval, 30 to 77 percent) in the number of total cerebrovascular accidents in the warfarin group as compared with the placebo group (44 vs. 20; P = 0.0015). Serious bleeding was noted in 0.6 percent of the warfarin-treated patients per year.. Long-term therapy with warfarin has an important beneficial effect after myocardial infarction and can be recommended in the treatment of patients who survive the acute phase.

Topics: Cerebrovascular Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Recurrence; Thromboembolism; Warfarin

Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke.. We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin.. A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients).. Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Prothrombin Time; Risk; Warfarin

The Stroke Prevention in Atrial Fibrillation Study recently found and reported (SPAF Investigators, N Engl J Med, 1990;322:863-868) a beneficial effect of both warfarin and aspirin compared with placebo in the primary prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Among warfarin-eligible patients, the event rates were 1.6%/yr for those receiving active antithrombotic therapy (warfarin or aspirin) and 8.3%/yr for those receiving placebo (p less than 0.00005) (risk reduction 81%, 95% confidence interval 56-91). Ironically, we did not find a beneficial effect of aspirin in warfarin-ineligible patients. On the basis of these results, the study has been reshaped to directly compare these two antithrombotic agents. Insight into the apparent aspirin unresponsiveness noted in some patients also is being sought. Interpretation of the preliminary results and the reshaping of the study have been made more complex by the continued blinding of the investigators to certain portions of the data. Presented is an account of the study from its inception through its recent redesign.

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Humans; Placebos; Warfarin

Atrial fibrillation, even in the absence of rheumatic valvular disease, predisposes patients to embolic complications, but the role of antithrombotic therapy in the prevention of such complications has not been fully clarified. We therefore performed a randomized, placebo-controlled trial to evaluate warfarin and aspirin individually as prophylaxis against ischemic stroke and systemic embolism (the primary events) in such patients. Patients eligible to receive warfarin (group 1) were assigned to warfarin (open label), aspirin (325 mg per day), or placebo (aspirin and placebo were given in a doubleblind fashion). Those who were not eligible for warfarin (group 2) received either aspirin or placebo in a double-blind fashion. The placebo arm of group 1 was recently terminated, when evidence emerged that each active agent was superior to placebo. In this paper we report preliminary data on active therapy (with either warfarin or aspirin) as compared with placebo in group 1, and on aspirin as compared with placebo in groups 1 and 2 combined. By November 1989, 1244 patients had been followed for a mean of 1.13 years. The event rates were 1.6 percent per year in the 393 patients who made up the two active treatment arms (warfarin and aspirin) of group 1, and 8.3 percent per year in the 195 patients who made up the placebo arm (P less than 0.00005) (risk reduction, 81 percent; 95 percent confidence interval, 56 to 91). In all 517 patients given aspirin, the rate of primary events (3.2 percent per year) was lower than that in the 528 patients given placebo (6.3 percent per year; P = 0.014) (risk reduction, 49 percent; 95 percent confidence interval, 15 to 69). However, we were unable to show a benefit of aspirin in patients over 75 years of age. These preliminary data indicate that antithrombotic therapy with warfarin or aspirin is effective in the short term in reducing the risk of stroke and systemic embolism in patients with atrial fibrillation due to causes other than rheumatic valvular disease. The relative benefits of aspirin and warfarin remain unclear, and the trial is continuing in order to address this issue.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Thromboembolism; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Randomized Controlled Trials as Topic; Warfarin

Topics: Aged; Aspirin; Canada; Cerebrovascular Disorders; Clinical Trials as Topic; Dipyridamole; Female; Heparin; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Placebos; Platelet Aggregation; Random Allocation; Risk; Sex Factors; Sulfinpyrazone; United States; Warfarin

Topics: Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Coronary Disease; Female; Fibrinolytic Agents; Heparin; Humans; Male; Myocardial Infarction; Phenindione; Pulmonary Embolism; Time Factors; United Kingdom; United States; United States Department of Veterans Affairs; Warfarin

Recent multicenter clinical trials using platelet-suppressive agents for the secondary prevention of myocardial infarction have yielded inconclusive results, although some of the data suggest possible benefits. For transient ischemic attacks, after carotid artery surgery has been eliminated as an option, aspirin is the drug of choice for men; for women, and for men in whom aspirin fails, warfarin sodium should be considered. Warfarin is indicated after insertion of cardiac prosthetic disk valves, and if systemic emboli occur, dipyridamole should be added. Patients with atrial fibrillation should be treated prophylactically with coumarin agents, but only if underlying organic heart disease is demonstrable.

Topics: Aspirin; Blood Platelets; Cerebrovascular Disorders; Clinical Trials as Topic; Coumarins; Decision Making; Female; Hemorrhage; Heparin; Humans; Male; Myocardial Infarction; Pregnancy; Sex Factors; Thromboembolism; 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

Topics: Age Factors; Aged; Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Diabetes Complications; Dicumarol; Electrocardiography; Female; Heart Failure; Hemorrhage; Heparin; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Phenindione; Placebos; Pulmonary Embolism; Recurrence; Sex Factors; Thrombophlebitis; Time Factors; 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

Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin.. Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant–naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia.. Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular dementia and 3.30 per 100 person-years for Alzheimer dementia). Compared with warfarin, DOAC showed a comparable risks of dementia, vascular dementia, and Alzheimer dementia. In subgroup analyses, DOAC was associated with a lower risk of dementia than warfarin, particularly in patients aged 65 to 74 years (hazard ratio, 0.815 [95% CI, 0.709–0.936]) and in patients with prior stroke (hazard ratio, 0.891 [95% CI, 0.820–0.968]). When comparing individual DOACs with warfarin, edoxaban was associated with a lower risk of dementia (hazard ratio, 0.830 [95% CI, 0.740–0.931]).. In this large Asian population with atrial fibrillation, DOAC showed a comparable risk of dementia with warfarin overall. DOACs appeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cerebrovascular Disorders; Dementia; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Warfarin

The need for anticoagulation treatment following bioprosthetic aortic valve replacement remains controversial. We investigated the associations of warfarin treatment with the risks of major adverse cardiac and cerebrovascular events, including mortality, bleeding incidents, and reoperation requirement after bioprosthetic aortic valve replacement surgery.. We identified 1086 patients who received first bioprosthetic aortic valve replacement between 2001 and 2010 using Taiwan's National Health Insurance Database. Patients were excluded for prior use of warfarin, warfarin use for >3 months, dual valve procedures, prior valve surgeries, or concomitant surgeries. Enrolled patients were divided into 2 groups according to whether they were warfarin-naïve or received warfarin for <3 months postsurgery. After propensity score matching, 282 patients not receiving warfarin were matched to 282 patients receiving warfarin for <3 months. Patients were followed-up for minimum 36 months.. Patients receiving warfarin were younger and showed less frequent kidney disease than those who did not use warfarin. The warfarin group demonstrated a gross decrease in major adverse cardiac and cerebrovascular events. Patients receiving warfarin for <30 days were at an even lower risk for major adverse cardiac and cerebrovascular events than those treated for ≥30 days. No significant difference in bleeding or reoperation risk was observed between warfarin users and warfarin nonusers. Similar findings remained after propensity-score matching but the benefit of short-term warfarin use diminished in a younger population.. Short-term use of postoperative warfarin (especially <30 days) following bioprosthetic aortic valve replacement may be associated with a reduction in MACCE compared with nonuse.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Bioprosthesis; Cerebrovascular Disorders; Databases, Factual; Drug Administration Schedule; Female; Heart Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Middle Aged; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome; Warfarin; Young Adult

In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients.. This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately.. Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups.. Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Italy; Longitudinal Studies; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Warfarin

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antilymphocyte Serum; Cerebrovascular Disorders; Child; Child, Preschool; Cyclosporine; Erythrocyte Transfusion; Female; Hemoglobinuria, Paroxysmal; Hemolysis; Heparin; Humans; Infant; Infant, Newborn; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Infarction; Neutropenia; Neutrophils; Registries; Retrospective Studies; Thromboembolism; Warfarin

To describe a case of subtherapeutic international normalized ratio (INR) associated with concomitant use of warfarin and banana flakes in a patient with diarrhea.. A man in his 30s was hospitalized for an elective procedure, but his stay was complicated by cerebral venous thrombosis requiring intravenous infusion of unfractionated heparin, ventilator-associated pneumonia, bacteremia requiring broad-spectrum antimicrobials and percutaneous endoscopic gastrostomy tube placement, and diarrhea. Eventually, the heparin was transitioned to warfarin. After several days of therapeutic INR, the INR became subtherapeutic and remained so for 3 days. The decreased INR correlated temporally with initiation of consistent administration of dried banana flakes to treat diarrhea and the subsequent decrease in the rate and extent of diarrhea. Diarrhea decreases the amount and activity of vitamin K-producing intestinal flora and dietary vitamin K absorption, resulting in increased INR. Resolution of diarrhea secondary to banana flakes administration in this patient may have contributed to the decreased INR by causing a relative increase in vitamin K-producing flora and vitamin K absorption. A probability score of 5 was obtained upon applying the Drug Interaction Probability Scale modified to address interactions between warfarin and dietary supplements, indicating a probable interaction between warfarin and banana flakes.. Concomitant use of warfarin and banana flakes supplements may result in a reduced rate and extent of diarrhea and may be associated with subtherapeutic INR and decreased warfarin efficacy. Practitioners must be aware of this potential interaction and closely monitor INR and adjust warfarin doses accordingly.

Topics: Adult; Anticoagulants; Cerebrovascular Disorders; Diarrhea; Dietary Supplements; Drug Interactions; Humans; International Normalized Ratio; Male; Musa; Venous Thrombosis; Vitamin K; Warfarin

Few large studies have evaluated the adverse events associated with therapeutic colonoscopy for colorectal neoplasia, including bleeding and bowel perforation. Our aim was to investigate factors associated with these events, using a Japanese national inpatient database.. We extracted data from the nationwide Japan Diagnosis Procedure Combination database for patients who underwent therapeutic colonoscopy for colorectal neoplasia between 2013 and 2014. Therapeutic colonoscopy included endoscopic submucosal dissection (ESD), EMR, and polypectomy. Outcomes included bleeding, perforation, cerebro-cardiovascular events, and in-hospital death. A multivariable logistic regression model was used to evaluate factors associated with bleeding and bowel perforation.. We analyzed 345,546 patients, including 16,812 (4.9%) who underwent ESD, 219,848 (63.6%) who underwent EMR, and 108,886 (31.5%) who underwent polypectomy. The rates of bleeding, bowel perforation, cardiovascular events, cerebrovascular events, and death were 32.5, 0.47, 0.05, 0.88, and 1.32 per 1000 patients, respectively. In the multivariate analysis, a higher bleeding rate was associated with being male, comorbid diseases, ESD, tumor size ≥2 cm, and use of drugs including low-dose aspirin, thienopyridines, non-aspirin antiplatelet drugs, novel oral anticoagulants, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids. A higher bowel perforation rate was associated with being male, renal disease, ESD, tumor size ≥2 cm, and drugs including warfarin, NSAIDs, and steroids.. Although the incidence of adverse events after therapeutic colonoscopy was low, several patient-related factors were significantly associated with bleeding and bowel perforation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebrovascular Disorders; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Comorbidity; Endoscopic Mucosal Resection; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Incidence; Intestinal Perforation; Japan; Kidney Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Sex Factors; Steroids; Tumor Burden; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticlopidine; Warfarin

The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation.. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs.. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group.. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chi-Square Distribution; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Pyridines; Republic of Korea; Retrospective Studies; Risk Factors; Stents; Time Factors; Treatment Outcome; Warfarin

Factors associated with cerebrovascular events (CVEs) after radiofrequency catheter ablation (RFA) of atrial fibrillation (AF) have not been well defined in elderly patients (≥65 years). The purpose of this study was to determine the prevalence and predictors of CVEs after RFA in patients with AF ≥65 years old, in comparison to patients <65 years, and with or without AF.. This study included 508 consecutive patients ≥65 years old (mean age: 70 ± 4 years), who underwent RFA for paroxysmal (297) or persistent (211) AF. A stratified group of 508 patients < 65 years old who underwent RFA for AF served as a control group. All patients were anticoagulated with warfarin for ≥3 months after RFA. A perioperative CVE (≤4 weeks after RFA) occurred in 0.8% and 1% of patients ≥65 and <65 years old, respectively (P = 1). Among the patients ≥65 years old who remained in sinus rhythm after RFA, warfarin was discontinued in 60% and 56% of the patients with a CHADS(2) score of 0 and ≥1, respectively. Paroxysmal AF, no history of CVE, and successful RFA were independent predictors of discontinuing warfarin. During a mean follow-up of 3 ± 2 years, a late CVE (>4 weeks after the RFA) occurred in 15 of 508 (3%) of patients ≥65 years old (1% per year) and in 5 of 508 (1%) patients <65 years old (0.3% per year, P = 0.03). Among patients ≥65 years old, age >75 years old (OR = 4.9, ±95% CI: 3.3-148.5, P = 0.001) was the only independent predictor of a CVE. Among patients <65 years old, body mass index was the only independent predictor of a late CVE (OR = 1.2, ±95% CI: 1.03-1.33, P = 0.02).. The risk of a periprocedural CVE after RFA of AF is similar among patients ≥65 and <65 years old. Late CVEs after RFA are more prevalent in older than younger patients with AF, and age >75 years old is the only independent predictor of late CVEs regardless of the rhythm, anticoagulation status, or the CHADS(2) score (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus and prior Stroke or transient ischemic attack).

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Patient Selection; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Warfarin

The aim of the present study was to assess whether elevated B-type natriuretic peptide (BNP) levels, as an objective marker of heart failure, is a predictor of subsequent thromboembolic events in patients with atrial fibrillation (AF) during oral anticoagulant therapy. This was a post hoc analysis of a single-center, prospective, observational study. Consecutive patients with AF (261 patients, 74 ± 9 years old, 153 paroxysmal AF) treated with warfarin were included for the analysis. BNP level at baseline examination was measured to assess the relationship of this parameter with subsequent thromboembolic events. BNP levels at the time of entry were 161 ± 188 (5-1,500, median 105) pg/ml. During an average follow-up time of 762 ± 220 (median 742) days, nine (1.8%/year) thromboembolic events occurred. Receiver operating characteristic curve showed that an optimal cut-off value for BNP to predict thromboembolic events was 218 pg/ml. There were six thromboembolic events observed among patients with a baseline BNP levels ≥200 pg/ml (n = 73) as compared to three such events in those with baseline BNP levels <200 pg/ml (n = 188). Kaplan-Meier curves for BNP level showed that elevated BNP level (≥200 pg/ml) was significantly associated with thromboembolic events (p < 0.01). Cox-proportional hazard analysis also revealed that a high BNP level (≥200 pg/ml) was a significant predictor of subsequent thromboembolic events (hazard ratio 5.32, p = 0.018). Elevated BNP levels (≥200 pg/ml) could be a useful marker of subsequent thromboembolic events in patients with AF during oral anticoagulant therapy. However, the number of patients and events in this study was small and drawing a definite conclusion was not possible with this small sample size. Therefore, further larger-scale, multicenter studies are needed to confirm these findings.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cerebrovascular Disorders; Chi-Square Distribution; Heart Failure; Humans; Japan; Kaplan-Meier Estimate; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Up-Regulation; Warfarin

What's known on the subject? and What does the study add? There is controversy over the use of anti-platelet and anti-coagulant drugs in men undergoing TURP with contradictory evidence on the effect of the drugs on bleeding following the operation, particularly for aspirin. If anti-platelet or anti-coagulant drugs are not stopped for TURP, there is an unacceptable burden of bleeding. If the drugs are stopped there is an unacceptable rate of cardiovascular events.. • To determine the morbidity associated with perioperative management of antiplatelet (AP) or anticoagulant (AC) medication and transurethral prostatectomy.. • A retrospective review was performed on 163 consecutive patients undergoing transurethural prostatectomy. • Patients were grouped according to the perioperative management of AP and AC medications: control patients not prescribed any AP/AC drugs (group 1), those on AP/AC who had ceased them perioperatively (group 2) and those whose AP/AC were continued (group 3). • Warfarin was withheld perioperatively for all patients. • Morbidity associated with increased blood loss and cardiovascular or cerebrovascular events was recorded and differences were analysed with SPSS version 16 software.. • There was a statistically significant increase in bleeding-associated morbidity in group 2 (13/65) and group 3 (6/7) compared with the controls (9/91) (P < 0.01). • Cardiovascular and cerebrovascular events were only seen in group 2 (6/65), statistically significantly higher than the event rate in the other groups (P ≤ 0.01). • All cardiovascular or cerebrovascular events occurred in patients prescribed these medications for secondary prevention.. • Patients taking AP or AC medications have a higher rate of perioperative bleeding compared with those who are not taking any. • However, for patients prescribed AP or AC medication for secondary prevention, withholding these medications results in an increased rate of cardiovascular and cerebrovascular complications. • Careful consideration of the risks and other management options should be undertaken before performing transurethural prostatectomy in this high risk group of patients.

Topics: Aged; Anticoagulants; Aspirin; Blood Loss, Surgical; Cardiovascular Diseases; Case-Control Studies; Cerebrovascular Disorders; Humans; Male; Perioperative Care; Platelet Aggregation Inhibitors; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Transurethral Resection of Prostate; Warfarin

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation; Cardiac Catheterization; Cerebrovascular Disorders; Coronary Angiography; Femoral Artery; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Radial Artery; Risk Assessment; Risk Factors; Treatment Outcome; Warfarin

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

In pulmonary arterial hypertension (PAH), thrombosis and thromboembolism occurs as a consequence of pulmonary microvasculopathy with a change of pulmonary vascular microenviroment toward a procoagulant, prothrombotic and antifibrinolytic pattern. Circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and prothrombotic cytokines have been identified in PAH patients so far. Thrombogenic pulmonary vasculopathy has been documented in many patients with PAH. Furthermore, most patients will not be diagnosed until right heart enlargement and impaired right ventricular function has developed. Thus, there is clear rationale for a treatment with anticoagulation. In four uncontrolled studies Warfarin improved the prognosis of patients with idiopathic and other forms of PAH. However, so far there are no prospective randomised studies evaluating the role of anticoagulants in the treatment of PAH. This review summarizes the current data and guidelines concerning anticoagulation in PAH.

Topics: Anticoagulants; Blood Platelets; Cardiomegaly; Cerebrovascular Disorders; Fibrinolysis; Humans; Hypertension, Pulmonary; Warfarin

Oral anticoagulation treatment with dicumarol preparations (warfarin sodium) is the standard in patients with atrial fibrillation. The effect of treatment depends on many factors, especially in elderly patients. In the study, we assessed the effect of treatment in patients with atrial fibrillation hospitalized in our cardiology ward from 2004 to 2005, in the form of a telephone survey (who controlled the treatment--general practitioner or internist?, the last 2 INR results, complications). INR 2.0-3.5 is considered an efficient therapeutic range. The proportion of permanently correctly anticoagulated patients is approximately 47% across the whole age range, the hypothesis of lower efficiency of treatment in elderly patients does not apply (48% of efficiently anticoagulated patients younger than 75 years vs. 46% of older patients--however, the study does not include polymorbid patients who could not take warfarin at all!) The fact whether a patient is monitored by a general practitioner or an outpatient specialist does not make any difference (49% of anticoagulated patients monitored by a general practitioner vs. 52% of patients monitored by an internist). The percentage of severe complications is relatively low (3.4%).

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Dicumarol; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Fibrinolytic Agents; Humans; Middle Aged; Platelet Aggregation Inhibitors; Warfarin

To describe the clinical course of patients undergoing vitreoretinal procedures while receiving systemic anticoagulation with warfarin.. We reviewed patient demographics, ocular findings, and clinical courses for 25 patients receiving systemic anticoagulation with warfarin who subsequently underwent vitreoretinal surgery.. Patient ages ranged from 49 years to 81 years (median, 69 years). Indications for anticoagulation included atrial fibrillation, cerebrovascular disease, deep vein thrombosis, prosthetic heart valves, and hypercoagulable state. Follow-up ranged from 4 months to 36 months (median, 19.5 months). The international normalized ratio ranged from 1.5 to 3.1 (median, 2.0). Final vision after surgery ranged from 20/20 to 20/400 (median, 20/100). One patient who underwent scleral buckling and external drainage of subretinal fluid had an intraoperative subretinal hemorrhage associated with the drainage procedure. In all other patients, no intraoperative complications occurred.. Cessation of therapy with warfarin may not be necessary in patients receiving anticoagulation who are undergoing vitreoretinal procedures. Successful visual and anatomical results may be achieved after vitreoretinal surgery for patients receiving anticoagulation with warfarin. The management of anticoagulation should occur in conjunction with the patient's internist to allow a clear understanding of the potential systemic risks of cessation of warfarin treatment preoperatively.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cryotherapy; Eye Diseases; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retinal Diseases; Retrospective Studies; Scleral Buckling; Thrombophilia; Venous Thrombosis; Vitrectomy; Vitreous Body; Warfarin

To review the frequency of hemorrhagic complications with sub-Tenon's anesthesia in patients on aspirin, warfarin or clopidogrel.. St. James's University Hospital, Leeds, United Kingdom.. Data were collected prospectively for patients having elective phacoemulsification under sub-Tenon's anesthesia. Seventy-five patients were on aspirin, 65 were on warfarin, and 40 were on clopidogrel. Seventy-five patients on no anticoagulants were used as the control group. No changes in the anticoagulant regimen were made prior to surgery.. No sight-threatening hemorrhagic complications were noted, and no surgery was postponed or cancelled due to an anesthesic complication. Subconjunctival hemorrhage occurred in 19% in the control group, 40% in the clopidogrel group, 35% in the warfarin group, and 21% in the aspirin group. The warfarin and clopidogrel groups had the highest incidence of subconjunctival hemorrhage (P<.05). The incidence of hemorrhages involving more than 1 quadrant was highest in these 3 groups; however, this did not achieve statistical significance (P = .37, Fisher exact test).. Data from this study support the continued use of anticoagulant agents among routine users during cataract surgery using a sub-Tenon's block.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Local; Anticoagulants; Aspirin; Cardiovascular Diseases; Cerebrovascular Disorders; Clopidogrel; Conjunctival Diseases; Connective Tissue; Eye Hemorrhage; Female; Humans; Lens Implantation, Intraocular; Male; Medical Audit; Middle Aged; Phacoemulsification; Prospective Studies; Risk Factors; Ticlopidine; Warfarin

Susac's syndrome is a rare disease of unknown aetiology affecting the small vessels of the retina, brain, and cochlea. We present the case of a 55-year-old female, the oldest patient yet described with the condition, and highlight the syndrome's clinical features.

Topics: Anti-Inflammatory Agents; Anticoagulants; Cerebral Angiography; Cerebrovascular Disorders; Cochlear Diseases; Cognition Disorders; Female; Hearing Disorders; Humans; Methylprednisolone; Middle Aged; Retinal Diseases; Syndrome; Warfarin

Although drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40-84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (> 3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took > or = 1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used > 4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4-8.5) for the risk of serious bleeding in patients treated with warfarin and > or = 1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1-18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Cerebrovascular Disorders; Chronic Disease; Drug Interactions; Female; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Incidence; Male; Middle Aged; Risk Factors; Thrombolytic Therapy; United Kingdom; Warfarin

We reviewed 22 patients who had undergone either carpal tunnel decompression or release of Dupuytren's contractures while anticoagulated with warfarin. All patients continued with their usual anticoagulant regime over the period of operation, provided that the international normalized ratio (INR) was 3 or less. There was no abnormal intraoperative or postoperative bleeding in any patient. Journal of Hand Surgery (British and European volume, 2004).

Topics: Anticoagulants; Cardiovascular Diseases; Carpal Tunnel Syndrome; Cerebrovascular Disorders; Dupuytren Contracture; Heart Valve Prosthesis; Humans; International Normalized Ratio; Outcome Assessment, Health Care; Warfarin

The indications for warfarin treatment in primary health care are increasing. An undertreatment with warfarin is reported in the prevention of embolic stroke in patients with chronic atrial fibrillation, and can be suspected for other indications. Information on the prevalence and incidence of diseases treated with warfarin would reveal useful data for audits concerning management of anticoagulant treatment. We aimed to assess warfarin treatment in primary health care with regard to prevalence, incidence, treatment diagnosis and patient characteristics.. A one-year retrospective study of electronic patient records up to May 2000 in primary health care in Stockholm, Sweden. Five primary health care centres with a registered population of 75 146. Main outcome measures were prevalence, incidence and treatment diagnosis.. Five hundred and seven patients, mean age 71.9 years, were on warfarin treatment. The prevalence was 0.67% (age-adjusted 0.75%), and it was significantly higher for men (0.78%) than for women (0.58%) (p = 0.01). In the age group 75-84 years the prevalence was 4.54%. The most prevalent treatment diagnosis was chronic atrial fibrillation (0.28%), which was more predominant for males (p = 0.02), followed by cerebrovascular disease (0.13%) and deep venous thrombosis (0.13%). The yearly incidence of warfarin treatment was 0.17%, with chronic atrial fibrillation as the predominant treatment diagnosis.. Warfarin treatment in primary health care is prevalent among the elderly. Chronic atrial fibrillation is the main treatment diagnosis. There is a gender difference favouring men in general and chronic atrial fibrillation as the treatment diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Incidence; Male; Middle Aged; Prevalence; Primary Health Care; Retrospective Studies; Risk Factors; Stroke; Sweden; Venous Thrombosis; Warfarin

The management of patients anticoagulated with warfarin and referred for coronary angiography presents a substantial challenge to the physician who must minimize risks of periprocedural hemorrhage and thromboembolism. The aim of this study was to evaluate the feasibility and safety of performing diagnostic coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Patients treated with warfarin were prospectively identified and enrolled in the study. Nineteen diagnostic cardiac catheterizations and six percutaneous coronary interventions were performed in 23 patients. The mean international normalized ratio was 2.4 +/- 0.5 (range, 1.8-3.5). Hemostasis was achieved with AngioSeal following 21 procedures and with Perclose following 4 procedures. No patient experienced a predefined endpoint. Specifically, no patient experienced procedure-related myocardial infarction, major or minor bleeding. We conclude that cardiac catheterization and percutaneous coronary intervention may be considered in the setting of uninterrupted warfarin therapy.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Cerebrovascular Disorders; Clopidogrel; Coronary Angiography; Coronary Disease; Equipment Design; Feasibility Studies; Female; Follow-Up Studies; Heart Failure; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Ticlopidine; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Age Factors; Aged; Cerebrovascular Disorders; Humans; International Normalized Ratio; Warfarin

In clinical practice, warfarin is underused for the prevention of stroke in individuals with atrial fibrillation despite unequivocal evidence of benefit and acceptable safety.. To ascertain, from primary care physicians, their beliefs and preferences regarding the use of warfarin in patients with atrial fibrillation.. A questionnaire was mailed to a random sample of 1000 primary care physicians in Ontario. Physician prescribing preferences from among treatment options available (warfarin, acetylsalicylic acid, ticlopidine, no therapy and other) were recorded for four separate scenarios of atrial fibrillation with varying degrees of risk for stroke. Physician perception of the risks associated with warfarin use and their awareness of the evidence of benefit were assessed.. Three hundred twenty-four physicians returned completed questionnaires. Among the four scenarios, physicians choosing not to use warfarin were three to six times more likely than physicians choosing to use warfarin to believe that there was inadequate evidence of benefit of warfarin for stroke prophylaxis, and they were four to six times more likely to be concerned about the risks of hemorrhage. These beliefs did not change significantly with scenarios describing patients with a high risk of stroke.. Physician reluctance to use warfarin is associated with a false understanding of the benefit to risk ratio, which arises from a low appreciation of therapeutic benefits and a high concern regarding hemorrhage.

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Data Collection; Decision Making; Drug Utilization; Hemorrhage; Humans; Ontario; Physicians, Family; Practice Patterns, Physicians'; Risk Factors; Surveys and Questionnaires; Warfarin

Cataract extraction in the warfarinized patient poses special considerations. Warfarin will increase the haemorrhagic risk but, more importantly, cessation or reduction in anticoagulation may well lead to serious thromboembolic phenomena. The purpose of this study was to assess the impact that warfarinization has on cataract extraction.. One thousand consecutive cataract extractions performed at Christchurch Hospital between 1996 and 1998 were reviewed. Twenty-eight patients (29 eyes) were on warfarin. Reasons for anticoagulation, modification to treatment regimen and postoperative outcome measures were available for 23 eyes or 79% of the study population.. The preoperative international normalized ratio (INR) ranged from 1.00 to 2.40+/-0.37 with a mean of 1.52. No thromboembolic phenomena occurred and four minor perioperative haemorrhages were noted, none of which affected the final visual outcome.. If warfarin is required to counteract serious thromboembolic tendencies, then it should not be ceased perioperatively. The small numbers of perioperative haemorrhages that did occur were not visually significant.

Topics: Anesthesia, Local; Anticoagulants; Cataract Extraction; Cerebrovascular Disorders; Coronary Disease; Eye Hemorrhage; Female; Humans; Male; Retrospective Studies; Warfarin

Complication rates of medical therapy for secondary stroke prevention derived from clinical trials may or may not be applicable to patients with cerebrovascular disease in the general population.. To determine complication rates for aspirin, warfarin, and intravenous heparin administered for secondary stroke prevention after first episodes of ischemic stroke, transient ischemic attack, or amaurosis fugax in a community.. Population-based historical cohort study.. Rochester, Minnesota.. All residents of Rochester who, between 1985 and 1989, received aspirin (n = 339) or warfarin (n = 145) within 2 years after first ischemic stroke, transient ischemic attack, or amaurosis fugax or received intravenous heparin (n = 201) within 2 weeks after first ischemic stroke, transient ischemic attack, or amaurosis fugax.. Occurrence of major complications caused by therapy.. Twenty aspirin-associated complications (1 fatal) occurred during an average 1.7 years of treatment, 8 warfarin-associated complications occurred during an average 0.7 years of treatment, and 3 heparin-associated complications (1 fatal) occurred during an average 5.1 days of treatment. Complication rates were 3.5 per 100 person-years (95% CI, 2.1 to 5.4) for aspirin, 7.9 per 100 person-years (CI, 3.4 to 15.6) for warfarin, and 0.30 (CI, 0.06 to 0.86) per 100 person-days for heparin. Rates of fatal complications were 0.2 per 100 person-years (CI, 0 to 1.0) for aspirin, 0 per 100 person-years (CI, 0 to 3.6) for warfarin, and 0.10 per 100 person-days (0 to 0.55) for heparin.. Complication rates for warfarin and intravenous heparin given as therapy for secondary stroke prevention in Rochester, Minnesota, were lower than rates reported from earlier trials and observational studies. However, complication rates for warfarin were higher than in more recent referral-based studies and multicenter randomized trials. After adjustment for duration of therapy, complication rates for heparin were higher than those for aspirin or warfarin. These rates can be used to judge the applicability of complication rates derived from ongoing clinical trials.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Cohort Studies; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Infusions, Intravenous; Male; Warfarin

Antithrombotic agents are underutilized in elderly patients with atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural patients were given antithrombotic therapy less often than rural patients for unclear reasons.. The charts of 597 hospitalized Medicare patients discharged between October 1, 1993, and December 31, 1994, from urban and rural hospitals in Missouri were reviewed. In addition to antithrombotic therapy prescribed at the time of discharge, patient and physician information, relative contraindications to antithrombotic therapy, and risk factors for stroke were identified. Rural and urban patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 87% of rural patients and in 84% of urban patients. Urban patients were more likely to have a relative contraindication to antithrombotic therapy compared with rural patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58% vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly more often than noncardiologists (69% vs 52%, P =.003).. Elderly rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high-risk profile and fewer relative contraindications. Primary care physicians prescribe antithrombotic therapy less often than cardiologists, which is one of the reasons for this underutilization.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Drug Utilization; Female; Fibrinolytic Agents; Humans; Logistic Models; Male; Medicare; Missouri; Practice Patterns, Physicians'; Risk Factors; Rural Population; Thrombolytic Therapy; United States; Warfarin

We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed.. We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Cardiotonic Agents; Cerebrovascular Disorders; Chronic Disease; Coronary Artery Bypass; Coronary Disease; Creatinine; Diabetes Complications; Digoxin; Female; Fibrinolytic Agents; Forecasting; Hemoglobins; Hospital Mortality; Humans; Hypertension; Logistic Models; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Nitrates; Reoperation; Risk Factors; Sex Factors; Survival Rate; Ventricular Function, Left; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Patient Selection; Warfarin

Physicians managing patients with nonvalvular atrial fibrillation must consider the risks, benefits, and costs of treatments designed to restore and maintain sinus rhythm compared with those of rate control with antithrombotic prophylaxis.. To compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin.. A Markov decision-analytic model was designed to simulate long-term health and economic outcomes.. Published literature and hospital accounting information.. Hypothetical cohort of 70-year-old patients with different baseline risks for stroke.. 3 months.. Societal.. Therapeutic strategies using different combinations of cardioversion alone, cardioversion plus amiodarone or quinidine therapy, and rate control with antithrombotic treatment.. Expected costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.. Strategies involving cardioversion alone were more effective and less costly than those not involving this option. For patients at high risk for ischemic stroke (5.3% per year), cardioversion alone followed by repeated cardioversion plus amiodarone therapy on relapse was most cost-effective ($9300 per QALY) compared with cardioversion alone followed by warfarin therapy on relapse. This strategy was also preferred for the moderate-risk cohort (3.6% per year), but the benefit was more expensive ($18,900 per QALY). In the lowest-risk cohort (1.6% per year), cardioversion alone followed by aspirin therapy on relapse was optimal.. The choice of optimal strategy and incremental cost-effectiveness was substantially influenced by the baseline risk for stroke, rate of stroke in sinus rhythm, efficacy of warfarin, and costs and utilities for long-term warfarin and amiodarone therapy.. Cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation. On relapse of arrhythmia, repeated cardioversion plus low-dose amiodarone is cost-effective for patients at moderate to high risk for ischemic stroke.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Combined Modality Therapy; Cost-Benefit Analysis; Decision Support Techniques; Electric Countershock; Female; Humans; Male; Markov Chains; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Recurrence; Risk Factors; Warfarin

To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation.. This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995.. In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0).. Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cross-Sectional Studies; Female; Humans; Logistic Models; Male; Odds Ratio; Practice Guidelines as Topic; Prospective Studies; Risk; Risk Factors; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Warfarin

Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF).. A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated.. The mean+/-SD age of 234 patients was 67.1+/-11.8 years, and 122 (52%) were women. Clinical risk factors were present in 74 of 80 patients (92%) aged >75 years compared with 99 of 154 patients (64%) 75 years of age, and was associated with clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72 of 154 (47%) to 105 of 154 (68%) patients aged 75 years, regardless of criteria used (P<0.01). Warfarin was being used in 55 of 105 patients (51%) 75 years (P<0.001). Anticoagulation was being undertaken in 7 of 49 patients (14%)

Topics: Aged; Aging; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Echocardiography; Female; Humans; Male; Middle Aged; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Utilization; Geriatrics; Hemorrhage; Humans; United States; Warfarin

To investigate the influence of dementia status on treatment for the secondary prevention of stroke in older patients.. Based on patient examinations and medical record review, we investigated the frequency of aspirin and/or warfarin use at hospital discharge for the prevention of recurrent stroke in older patients hospitalized with acute ischemic stroke.. A large academic medical center.. A cohort of 272 patients, mean age 72.1 +/- 8.5 years.. We performed neurologic examinations and reviewed medical records to investigate the effects of a clinical diagnosis of dementia and other potentially relevant factors on treatment with aspirin or warfarin at hospital discharge.. Thirty-one patients (11.4%) were not prescribed aspirin or warfarin at hospital discharge. Logistic regression determined that dementia (odds ratio (OR) = 2.57, 95% confidence interval (CI), 1.04-6.30) was a significant independent determinant of nontreatment with aspirin or warfarin, adjusting for abnormal gait (OR = 2.01, CI, .88-4.59); discharge to a nursing home or other institutional residence (OR = 2.55, CI, .83-7.81); cardiac disease (OR = .39, CI, .16-.95); cortical infarct location (OR = .45, CI, .18-1.10); male sex (OR = .47, CI, .20-1.15); age 80+ (OR = 1.14, CI, .46-2.82) and age 70-79 (OR = .96, CI, .32-2.88) versus age 60-69.. Our results suggest that dementia is a significant independent determinant of nontreatment with aspirin or warfarin when otherwise indicated for the prevention of recurrent stroke. The underutilization of aspirin and warfarin in older stroke patients with dementia may be a modifiable basis for their increased risk of recurrence and death.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Cerebrovascular Disorders; Dementia; Drug Utilization; Female; Geriatric Assessment; Humans; Logistic Models; Male; Middle Aged; Neurologic Examination; Patient Discharge; Patient Selection; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Warfarin

Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.. We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.. The use of warfarin increased 4-fold from 13% in 1990 to 50% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.. Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Therapy; Electrocardiography; Female; Humans; Incidence; Male; Prevalence; Treatment Outcome; Warfarin

Topics: Accidental Falls; Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Decision Support Techniques; Fibrinolytic Agents; Hematoma, Subdural; Humans; Life Expectancy; Markov Chains; Risk Factors; Treatment Outcome; Warfarin

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Contraindications; Depression; Drug Utilization; Female; Humans; Male; Malpractice; Platelet Aggregation Inhibitors; Residence Characteristics; Retrospective Studies; Risk Factors; Serum Albumin; Sex Factors; Warfarin

To study how many elderly inpatients with previously diagnosed atrial fibrillation were not receiving anticoagulant prophylaxis, and the prevalence of additional risk factors in these patients.. All new admissions to a department of medicine for the elderly were screened for atrial fibrillation. Additional risk factors were analysed in those with established atrial fibrillation who were not receiving warfarin. Previous hospital admissions, documentation of why prophylaxis was not being used and use of aspirin as an alternative agent were also examined.. 56 patients had previously diagnosed atrial fibrillation; 82% were not taking warfarin and 71% of these were not on aspirin either. All patients not taking warfarin had one additional risk factor for stroke and 95% had two or more. Fifty-two percent had attended hospital when atrial fibrillation was present within the previous 3 years and there was nothing documented in their records to explain why anticoagulation had not been used.. Most elderly inpatients with established atrial fibrillation were not taking warfarin. All had additional risk factors for stroke, which increase the absolute benefit of anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Therapy; Female; Humans; Male; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Warfarin

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cerebrovascular Disorders; Combined Modality Therapy; Electric Countershock; Humans; Treatment Outcome; Warfarin

To describe an unusual hemorrhagic complication associated with pupillary dilation in a patient with exfoliation glaucoma taking anticoagulation therapy.. A 78-year-old woman with bilateral exfoliation glaucoma who was receiving warfarin, 2 mg daily, for systemic anticoagulation developed acute visual loss in the right eye several hours after pupillary dilation.. Examination disclosed bilateral advanced exfoliation glaucoma, localized vascularized iridolenticular adhesions in the right eye, and a 4-mm layered hyphema in the right eye.. Patients with exfoliation glaucoma and vascularized posterior synechiae who are receiving anticoagulation therapy are at increased risk for visually significant spontaneous hyphema after pupillary dilation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Carbachol; Cerebrovascular Disorders; Drug Therapy, Combination; Exfoliation Syndrome; Female; Glaucoma; Humans; Hyphema; Latanoprost; Propranolol; Prostaglandins F, Synthetic; Pupil; Warfarin

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

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Fibrinolytic Agents; Humans; Risk Factors; Warfarin

Topics: Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Cerebrovascular Disorders; Heart Diseases; Humans; Risk; Thrombolytic Therapy; Thrombosis; Warfarin

We sought to determine the influence of plaque morphology and warfarin anticoagulation on the risk of recurrent emboli in patients with mobile aortic atheroma.. An epidemiologic link between aortic atheroma and systemic emboli has been described both in pathologic and transesophageal studies. Likewise, a few studies have found an increased incidence of recurrent emboli in these patients. The therapeutic implications of these findings has not been studied.. Thirty-one patients presenting with a systemic embolic event and found to have mobile aortic atheroma were studied. The height, width and area of both immobile and mobile portions of atheroma were quantitated. The dimensions of the mobile component was used to define three groups: small, intermediate and large mobile atheroma. The patients were followed up by means of telephone interview and clinical records, with emphasis on anticoagulant use and recurrent embolic or vascular events.. Patients not receiving warfarin had a higher incidence of vascular events (45% vs. 5%, p = 0.006). Stroke occurred in 27% of these patients and in none of those treated with warfarin. The annual incidence of stroke in patients not taking warfarin was 0.32. Myocardial infarction occurred in 18% of patients also in this group. Taken together, the risk of myocardial infarction or stroke was significantly increased in this group (p = 0.001). Forty-seven percent of patients with small, mobile atheroma did not receive warfarin. Recurrent stroke occurred in 38% of these patients, representing an annual incidence of 0.61. There were no strokes in patients with small, mobile atheroma treated with warfarin (p = 0.04). Likewise, none of the patients with intermediate or large mobile atheroma had a stroke during follow-up. Only three of these patients had not been taking warfarin.. Patients presenting with systemic emboli and found to have mobile aortic atheroma on transesophageal echocardiography have a high incidence of recurrent vascular events. Warfarin is efficacious in preventing stroke in this population. The dimension of the mobile component of atheroma should not be used to determine the need for anticoagulation.

Topics: Aged; Anticoagulants; Aortic Diseases; Arteriosclerosis; Cerebrovascular Disorders; Coronary Thrombosis; Echocardiography, Transesophageal; Female; Humans; Male; Middle Aged; Recurrence; Treatment Outcome; Warfarin

A 50-year-old man presented spontaneous internal carotid artery dissection with ischemic stroke. He had a history of deep venous thrombosis, and an activated protein C resistance due to factor V Leiden mutation was documented. He showed no other vascular risk factor. This unusual case puts the question whether this coagulation defect may be related to the stroke occurrence.

Topics: Anticoagulants; Aortic Dissection; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebrovascular Disorders; Factor V; Follow-Up Studies; Heparin; Humans; Male; Middle Aged; Point Mutation; Protein C; Thrombophlebitis; Warfarin

Large multicenter trials have evaluated the benefit of different medical and surgical therapies to prevent stroke. However, the application of trial results to clinical practice remains uncertain for some areas of stroke prevention and has been discussed passionately among international experts. As part of a worldwide survey, the purpose of this analysis was to provide an informative and comparative view of the current practice of leading experts in North America (NA) and Western Europe (WE), where most of the large prevention trials have been performed.. The survey was performed worldwide among 185 neurologists who are currently leading the discussions of stroke prevention practices. It contained questions on the use of antiplatelet agents, oral anticoagulation, and surgery for the prevention of ischemic stroke. The population of this present analysis is the two groups of experts from WE (n=73) and NA (n=48) exclusively.. Of each group, >90% responded to the survey. Nearly all respondents reported prescribing aspirin in patients at risk of atherothrombotic stroke, but significant differences between NA and WE are shown by the recommended doses (P<.0001): aspirin doses of >500 mg daily are given exclusively by American participants (36%), whereas doses <200 mg are recommended only in Europe (51%). Eighty-six percent of American versus 59% of European respondents reported using ticlopidine as their second choice (P<.005), and 23% of respondents from WE used warfarin compared with 5% from NA (P<.05). The reported use of anticoagulants in patients with atrial fibrillation increased in accordance with the patient's individual risk of stroke, but respondents from WE were more reluctant to use anticoagulants in patients older than 75 years. Relatively higher target international normalized ratio values were reported by European respondents. Nearly all participants recommend carotid endarterectomy in patients with symptomatic carotid stenosis. The use of carotid endarterectomy in asymptomatic patients was significantly more common among responding experts from NA (48% versus 28%; P<.05), particularly in patients with >95% stenosis (89% versus 53%; P<.0005).. This analysis shows significant differences in several areas of stroke prevention practices between leading experts from NA and WE. These differences may be explained partly by divergent results of trials from the two continents, but in some areas of controversy currently available trial data are not sufficient to form an international consensus to guide daily clinical practice.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Endarterectomy, Carotid; Europe; Fibrinolytic Agents; Humans; Middle Aged; North America; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biological Availability; Cerebrovascular Disorders; Chemistry, Pharmaceutical; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Costs; Drugs, Generic; Humans; Patient Selection; Therapeutic Equivalency; Thromboembolism; Warfarin

Stroke is a catastrophic, but largely preventable, consequence of AF. ASHP supports recommendations established by the American College of Chest Physicians (Table 1) for the use of antithrombotic therapy in appropriate patients to reduce the morbidity and mortality associated with stroke. The selection of warfarin versus aspirin should be based on the presence of clinical risk factors for stroke and the patient's ability to safely undergo anticoagulation therapy. Adequate patient education and monitoring are keys to the successful use of antithrombotic therapy, and ASHP believes that pharmacists can play an important role in providing these services.

Topics: Adult; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Cost-Benefit Analysis; Humans; Middle Aged; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Thrombosis; Warfarin

To investigate a population of elderly people for atrial fibrillation and to determine how many of the cases identified might benefit from treatment with anticoagulants.. From a practice of four primary care physicians, 1422 patients aged 65 years and over were identified, of whom 1207 (85% of the total population) underwent electrocardiographic screening to detect the presence of atrial fibrillation. Patients with the arrhythmia were further evaluated by echocardiography and interview, to stratify their risk of stroke based on echocardiographic and clinical risk factors, their perceived risk from anticoagulation, and their attitude towards this treatment. Their primary care physician was also interviewed to determine the factors influencing the prescription of anticoagulants.. The arrhythmia occurred in 65 patients (5.4% overall), its prevalence increasing markedly with age (2.3% in 65 to 69 years age group; 8.1% in those over 85). Warfarin was being prescribed to 21.4% of these patients, although the findings of the study indicate that a further 20% were eligible for this treatment. Symptoms suggestive of cardiac failure were common (32.1%) and coexisting pathology was often identified by cardiac ultrasound in these patients (left ventricular hypertrophy, 32.1%; impaired left ventricular contractility, 21.4%; left atrial dilation, 80.4%; mitral annular calcification, 42.9%; mitral stenosis, 7.1%; mitral regurgitation, 48.2%; aortic stenosis, 8.9%). In all but one case, the decision to anticoagulate was based on the clinical rather than the echocardiographic findings.. Individual risk-benefit assessment in elderly patients with atrial fibrillation suggests that almost half (41.4%) are eligible for full anticoagulation with warfarin, whereas presently only one fifth are receiving this treatment. The decision to anticoagulate can be made on clinical grounds in most cases. If these results are confirmed, a doubling of the current number of patients taking anticoagulants can be anticipated.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Echocardiography; Electrocardiography; Family Practice; Humans; Mass Screening; Patient Selection; Prevalence; Risk Assessment; Warfarin

Topics: Anticoagulants; Cerebrovascular Disorders; Guidelines as Topic; Humans; Thrombosis; Warfarin

Studies of selected populations suggest that anticoagulation in atrial fibrillation is underused and that nonclinical factors influence the use of this stroke-preventing therapy. We wished to examine recent national trends and predictors of warfarin sodium use in atrial fibrillation.. A nationally representative sample of office visits from the 1989 to 1996 National Ambulatory Medical Care Surveys was used. We selected 1125 visits by patients with atrial fibrillation, including 877 visits to cardiologists and primary care physicians in which apparent contraindications for anticoagulation were absent. The principal outcome measure was the proportion of visits with warfarin reported. We analyzed trends in warfarin use and statistically evaluated the predictors of warfarin use. Warfarin use increased from 13% of atrial fibrillation visits in 1989 to 40% in 1993 (P for trend <.001) in patients without contraindications. Between 1993 and 1996, however, there was no change in warfarin use. Independent of other factors, warfarin was significantly more likely to be reported in patients with a history of stroke and in patients residing outside of the South.. Warfarin use in atrial fibrillation has not increased recently, indicating inadequate implementation of this highly effective therapy. Barriers to anticoagulation in real-world clinical practice need to be identified and addressed.

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Health Care Surveys; Humans; Practice Patterns, Physicians'; United States; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Middle Aged; Warfarin

Recent atrial fibrillation guidelines recommend the incorporation of patient preferences into the selection of antithrombotic therapy. However, no trial has examined how incorporating such preferences would affect quality-adjusted survival or medical expenditure. We compared 10-year projections of quality-adjusted survival and medical expenditure associated with two atrial fibrillation treatment strategies: warfarin-for-all therapy versus preference-based therapy. The preference-based strategy prescribed whichever antithrombotic therapy, warfarin or aspirin, had the greater projected quality-adjusted survival.. We used decision analysis stratified by the number of stroke risk factors (history of stroke, transient ischemic attack, hypertension, diabetes, or heart disease). The base case focused on compliant 65-year-old patients who had nonvalvular atrial fibrillation and no contraindications to antithrombotic therapy.. In patients whose only risk factor for stroke was atrial fibrillation, preference-based therapy improved projected quality-adjusted survival by 0.05 quality-adjusted life year (QALY) and saved $670. For patients who had atrial fibrillation and one additional risk factor for stroke, preference-based therapy improved quality-adjusted survival by 0.02 QALY and saved $90. In patients who had atrial fibrillation and multiple additional risk factors for stroke, preference-based therapy increased medical expenditures and did not improve quality-adjusted survival substantially. The benefits of preference-flexible therapy arose from the minority of patients who would have had a longer quality-adjusted survival if they had been prescribed aspirin rather than warfarin.. As do risks of stroke and of hemorrhage, patients' preferences help to determine which antithrombotic therapy is optimal. Preference-based treatment should improve quality-adjusted survival and reduce medical expenditure in patients who have nonvalvular atrial fibrillation and not more than one additional risk factor for stroke.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Cohort Studies; Cost-Benefit Analysis; Decision Trees; Embolism; Female; Health Care Costs; Humans; Male; Middle Aged; Patient Satisfaction; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Thrombolytic Therapy; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cerebrovascular Disorders; Chronic Disease; Decision Making; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cerebrovascular Disorders; Chronic Disease; Dose-Response Relationship, Drug; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Risk Factors; Warfarin

Several large prospective randomized trials have demonstrated that anticoagulation with warfarin reduces the risk of thromboembolic stroke in high risk patients with chronic AF by approximately 70%. Large numbers of patients with permanent pacemakers have AF, and anticoagulation rates in this population have not been described. In a prospective analysis of 110 consecutive patients attending the pacemaker clinic of a large university hospital we assessed the number of patients with AF and the proportion of these patients who were receiving anticoagulation to prevent thromboembolic stroke. Where necessary, temporary pacemaker reprogramming to low ventricular rates was utilized to facilitate the diagnosis of AF. Fifty-three of the 110 patients (48%) were diagnosed with AF, all of whom (100%) had accepted high risk factors for thromboembolic stroke. Only eight of the 53 (15%) had been anticoagulated with warfarin. Thirty-six of the 53 patients (68%) diagnosed with AF had no prior documented diagnosis of chronic AF, and the majority had no symptoms suggesting AF. A single lead II ECG was insufficient in 67 of the 110 patients (61%) to diagnose the underlying atrial rhythm; the remainder required 12-lead ECGs or temporary pacemaker reprogramming to low ventricular rates to diagnose the underlying atrial rhythm. AF is common in patients with permanent pacemakers. It is commonly asymptomatic, and anticoagulation is markedly underutilized in reducing stroke risk in these patients. Attention to the possibility of AF in paced patients should allow prompt diagnosis and allow both the initiation of anticoagulation in order to reduce thromboembolic stroke risk and consideration for cardioversion of AF to sinus rhythm.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Electrocardiography; Female; Humans; Male; Pacemaker, Artificial; Prevalence; Prospective Studies; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Cerebrovascular Disorders; Humans; Long-Term Care; Risk Factors; Warfarin

Topics: Accidental Falls; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Utilization; Hemorrhage; Homes for the Aged; Humans; Nursing Homes; 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

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Cohort Studies; Dose-Response Relationship, Drug; Family Practice; Female; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Prospective Studies; Risk; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation.. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature.. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring.. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Disorders; Cost-Benefit Analysis; Humans; Longevity; Risk Assessment; Sensitivity and Specificity; Thrombosis; Warfarin

Topics: Aged; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Female; Humans; Male; Middle Aged; Risk Factors; Warfarin

To determine the incidence and nature of hemorrhagic complications in patients having phacoemulsification and foldable intraocular lens (IOL) implantation while taking aspirin or warfarin.. The Jules Stein Eye Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.. This retrospective study reviewed the charts from the practice of 1 ophthalmic surgeon. The type of medication, dosage, indication for anticoagulant therapy, type of incision, type of anesthesia, and intraoperative and postoperative hemorrhagic complications were recorded.. Sixty-two patients (82 eyes) taking aspirin and 25 patients (31 eyes) taking warfarin were identified. Seven eyes in the aspirin group (8.5%) and 3 in the warfarin group (9.7%) experienced subconjunctival hemorrhages. Eight of the 10 subconjunctival hemorrhages occurred in eyes with scleral incisions. The remaining 2 occurred in eyes with corneal incisions. No eye developed lid ecchymosis, retrobulbar hemorrhage, hyphema, or suprachoroidal hemorrhage.. Phacoemulsification with foldable IOL implantation was performed safely in patients taking aspirin or warfarin. Subconjunctival hemorrhage was the most common hemorrhagic complication.

Topics: Anticoagulants; Aspirin; Cardiovascular Diseases; Cerebrovascular Disorders; Conjunctival Diseases; Eye Hemorrhage; Humans; Lens Implantation, Intraocular; Phacoemulsification; Retrospective Studies; Warfarin

Elderly patients with ischemic stroke and atrial fibrillation are at especially increased risk for recurrent stroke. Warfarin sodium is highly effective in reducing this risk.. To determine the use of warfarin among a population sample of elderly patients with atrial fibrillation hospitalized for ischemic stroke.. The Connecticut Peer Review Organization conducted a chart review of Medicare patients, aged 65 years or older, hospitalized in 1994 with a diagnosis of atrial fibrillation. Patients with a principal diagnosis of acute myocardial infarction or another indication for anticoagulation were excluded.. Among 635 patients (402 women; 585 white; 218 > or =85 years old; 147 with a new diagnosis of atrial fibrillation), 334 had stroke as a principal diagnosis. Among those discharged alive after a stroke, only 147 (53%) of 278 were prescribed warfarin at discharge. Furthermore, among 130 (47%) of 278 patients not prescribed warfarin at discharge, 81 (62%) of 130 were also not prescribed aspirin. Increased potential benefit (additional vascular risk factors) was not associated with a higher rate of warfarin use. Low risk for anticoagulation (lack of risk factors for bleeding) was associated with a slightly higher rate of warfarin use. Among those with an increased risk of stroke and a low risk for bleeding (ideal candidates), 124 (62%) of 278 were discharged on a regimen of warfarin.. Anticoagulation of elderly stroke patients with atrial fibrillation, even among ideal candidates, is underused. The increased use of warfarin among these patients represents an excellent opportunity for reducing the risk of recurrent stroke in this high-risk population.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Drug Utilization; Female; Humans; Male; Medical Records; Medicare; Recurrence; Retrospective Studies; Risk; United States; Warfarin

To investigate the prevalence of the use of warfarin to maintain an international normalized ratio (INR) between 2.0 and 3.0 in older persons with chronic nonvalvular atrial fibrillation (AF), and without contraindications to warfarin, who are at high risk for developing new thromboembolic (TE) stroke.. A retrospective analysis of charts from all older persons seen during 1997 at an academic hospital-based geriatrics practice.. An academic hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians.. Three hundred eighty men and 1183 women, mean age 80+/-8 years (range 59 to 103 years), were included in the study.. Of 1563 persons studied, 141 (9%) had chronic nonvalvular AF. Of 141 persons with AF, 127 (90%) were at high risk for developing TE stroke because they had either a previous thromboembolism, congestive heart failure, or echocardiographic evidence of abnormal left ventricular systolic function; a systolic blood pressure >160 mm Hg; or they were women older than 75 years of age. Of the 127 persons with AF at high risk for developing TE stroke, three (2%) had contraindications to warfarin. Of the 124 persons with AF at high risk for developing TE stroke and no contraindications to warfarin, 61 (49%) were treated with warfarin to maintain an INR between 2.0 and 3.0, and 45 (36%) were treated with 325 mg aspirin daily. Of 14 persons with AF at low risk for developing TE stroke, one (7%) was treated with warfarin to maintain an INR between 2.0 and 3.0, and six (43%) were treated with 325 mg aspirin daily.. Warfarin is underutilized as a treatment to maintain an INR between 2.0 and 3.0 in older persons with chronic nonvalvular AF at high risk for developing TE stroke.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Drug Utilization; Female; Geriatrics; Humans; International Normalized Ratio; Male; Medical Audit; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Comorbidity; England; Humans; Prevalence; Warfarin

Topics: Anticoagulants; Cardiac Surgical Procedures; Cerebrovascular Disorders; Child; Cognition; Female; Heart Septal Defects, Atrial; Humans; Intracranial Embolism and Thrombosis; Postoperative Complications; Protein C Deficiency; Warfarin

Using a decision-analytic model, we sought to examine the cost-effectiveness of three strategies for cardioversion of patients admitted to the hospital with atrial fibrillation.. Transesophageal echocardiographic (TEE)-guided cardioversion has been proposed as a method for early cardioversion of patients with atrial fibrillation. The cost-effectiveness of this approach, relative to conventional therapy, has not been studied.. We ascertained the cost per quality-adjusted life-year (QALY) of three strategies: 1) conventional therapy--transthoracic echocardiography (TTE) and warfarin therapy for 1 month before cardioversion; 2) initial TTE, followed by TEE and early cardioversion if no thrombus is detected; 3) initial TEE, with early cardioversion if no thrombus is detected. With strategies 2 and 3, if a thrombus is seen, follow-up TEE is performed. If no thrombus is seen, cardioversion is then performed. All strategies utilized anticoagulation before and extending for 1 month after cardioversion. Life expectancy, utilities (quality-of-life weights) and event probabilities were ascertained from published reports. Cost estimates were based on published data and hospital accounting information.. Transesophageal echocardiographic-guided early cardioversion (strategy 3: cost $2,774, QALY 8.49) dominates TTE/TEE-guided cardioversion (strategy 2: cost $3,106, QALY 8.48) and conventional therapy (strategy 1: cost $3,070, QALY 8.48) because it is the least costly with similar effectiveness. Sensitivity analyses demonstrated that TEE-guided cardioversion (strategy 3) dominates conventional therapy if the risk of stroke after TEE negative for atrial thrombus is slightly less than that after conventional therapy (baseline estimate 0.8%). The results also depend on the risk of major hemorrhage but are less sensitive to baseline estimates of morbidity from TEE, cost of TTE, cost of hospital admission for cardioversion and utilities for health states.. On the basis of a decision-analytic model, TEE-guided early cardioversion, without TTE, is a reasonable cost-saving alternative to conventional therapy for patients admitted to the hospital with atrial fibrillation. Such a strategy appears particularly beneficial for patients with an increased risk of hemorrhagic complications. Future clinical studies examining the TEE strategy should consider eliminating initial TTE and carefully assess both the thromboembolic and hemorrhagic risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Support Techniques; Echocardiography; Echocardiography, Transesophageal; Electric Countershock; Female; Heart Diseases; Hemorrhage; Humans; Male; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Thrombosis; Time Factors; Warfarin

By 1992, several prospective trials established the efficacy of anticoagulation (AC) and to some extent antiplatelet (AP) agents in the prevention of stroke in the setting of atrial fibrillation (AF). The objective of this study was to determine whether practice patterns in AF stroke prophylaxis reflect the findings of clinical trials and whether stroke prophylaxis in AF differs between community hospitals and tertiary teaching hospitals.. Retrospectively, 1250 hospital charts were reviewed. After patients who had undergone recent surgery, received treatment for malignancy, or were not in chronic AF on discharge were eliminated, 651 remaining records were analyzed for the presence of 26 clinical factors influencing the selection of thromboembolism prophylaxis. Descriptive statistics and logistic regression were used to analyze the association between clinical and demographic factors and the decision to treat with AC, AP, or no specific antiembolic therapy.. Of the 651 patients in AF, 273 (42%) received noemboli prophylaxis while 219 (34%) were treated with AC (warfarin), 146 (22%) were treated with AP, and 13 (2%) received both agents. Patients discharged in AF from community hospitals were significantly less likely to be treated with either AC or AP agents than patients discharged from tertiary centers. A strong bias against thromboembolism prophylaxis with either AC or AP agents in AF existed with age over 45 years. Multivariate logistic regression indicated that the decision to treat was associated only with the presence of prosthetic valve, history of prior stroke, mitral disease, and absence of a recent gastrointestinal bleed or occult blood in stool. Even after adjustment for these factors, a significant bias against treatment with either AC or AP agents with advancing age and discharge from community hospitals remained.. Thromboembolism prophylaxis with either AC or AP agents is underutilized in the setting of AF. Furthermore, factors known to increase the risk of embolization in AF such as age, hypertension, diabetes, and heart disease were not associated with decisions to treat with either AP or AC agents. This study suggests that the use of clinical guidelines suggested by trials of thromboembolism prophylaxis in AF could reduce the incidence of stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hospitals, Community; Hospitals, Teaching; Humans; Intracranial Embolism and Thrombosis; Medical Records; Middle Aged; Mitral Valve Stenosis; Multivariate Analysis; New York; Occult Blood; Platelet Aggregation Inhibitors; Regression Analysis; Retrospective Studies; Warfarin

Warfarin can strikingly prevent stroke in patients with NRAF with or without a history of stroke or TIA. The target degree of anticoagulation is an INR between 2.0 and 3.0. Any degree of anticoagulation with less than an INR of 2.0 will not provide full protection, any greater anticoagulation is no more effective, and an INR greater than 4.0 increases the risk of hemorrhage. Patients 65 years or younger without any risk factor do no better with warfarin than with aspirin or placebo, and should not be anticoagulated. All older patients or those with risk factors but without contraindications gain significant stroke prevention with warfarin anticoagulation as recommended above.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Incidence; Risk Factors; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Foundations; Humans; Male; Middle Aged; Mississippi; Patient Education as Topic; Risk Factors; Warfarin

Patients with left atrial thrombus are considered at high risk for thromboembolic events. The actual prognosis of these patients and the features most predictive of future events are unclear. We performed transesophageal echocardiograms in 2,894 patients over a 6 1/2-year period; 94 (age 69 +/- 11 years, 59 men, 83 in atrial fibrillation) were found to have left atrial thrombus. The thrombi were considered mobile in 45 patients and 33 patients had thrombus with a maximum dimension > or = 1.5 cm. Seven of the 94 patients with prosthetic valves were excluded from follow-up analysis. Over a follow-up period of 25.3 +/- 19.2 months, 17 patients had suffered a stroke or embolic event (event rate 10.4% per year) and 27 had died (mortality 15.8% per year). Cox proportional hazard regression analysis identified a maximum thrombus dimension > or = 1.5 cm (RR 19, p = 0.002), history of thromboembolism (RR 4.2, p = 0.038), and mobile thrombus (RR 5.3, p = 0.02) as predictors of subsequent thromboembolism. Moderate or severe left ventricular dysfunction was the only significant predictor of death (RR 2.9, p = 0.04). Gender, age, warfarin therapy at follow-up, atrial fibrillation, location (cavity vs appendage) of thrombus, and spontaneous echocardiographic contrast were not significant. Aggressive antithrombotic therapy may be indicated in these high-risk patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Echocardiography, Transesophageal; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Forecasting; Heart Atria; Heart Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prognosis; Proportional Hazards Models; Risk Factors; Sex Factors; Survival Rate; Thromboembolism; Thrombosis; Ventricular Dysfunction, Left; Warfarin

Topics: Anticoagulants; Aortic Arch Syndromes; Cerebrovascular Disorders; Diabetes Complications; Diabetic Angiopathies; Female; Hemiplegia; Humans; Ischemia; Leg; Middle Aged; Postoperative Complications; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

Stroke is uncommon after orthotopic liver transplantation. We offer the first report, to our knowledge, of two posttransplant patients with stroke associated with elevated anticardiolipin antibodies, and we discuss their management, including the use of immunosuppression and antithrombotic therapy. We suggest that anticoagulation is the treatment of choice for such patients.

Topics: Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Cerebrovascular Disorders; Female; Humans; Immunoglobulin G; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Warfarin

While the benefits of warfarin sodium therapy for stroke prevention in patients with atrial fibrillation (AF) have been extensively documented, generalizing clinical trial results to the majority of elderly persons with AF, especially to those who reside in the long-term care setting, remains challenging.. To determine the prevalence of AF in the institutionalized elderly population and the proportion receiving anticoagulation therapy with warfarin: to identify the clinical and functional characteristics of institutionalized elderly persons with AF that are associated with the use of warfarin; and to assess the quality of prescribing and monitoring of warfarin therapy in institutionalized elderly persons with AF.. This study involved 30 long-term care facilities (total No. of beds, 6437) located in New England, Quebec, and Ontario. The proportion of patients with AF who were receiving treatment with warfarin was determined. The association between clinical and functional characteristics and the use of warfarin was examined with crude and multivariable-adjusted analyses. For study subjects with at least 2 weeks of warfarin therapy during the 12-month period preceding the date of medical record abstraction, we assessed the quality of warfarin prescribing based on all international normalized ratio or prothrombin time ratio values during this period.. An electrocardiogram indicating AF was present in the records of 413 of 5500 long-term care residents (7.5%); 32% of such patients were being treated with warfarin. Only a history of stroke was found to be positively associated with the use of warfarin in this setting. Patients with a diagnosis of dementia and those in the oldest age group (> or = 85 years) were less likely to receive warfarin therapy. Warfarin was commonly prescribed to patients with a history of bleeding, substantial comorbidity and functional impairment, a history of falls, or concomitant potentiating drug therapy. Patients were maintained above or below the recommended therapeutic range 60% of the time.. Atrial fibrillation is common in patients residing in long-term care facilities, but its management with warfarin is highly variable. A more systematic approach to decision making regarding the use of warfarin for stroke prevention in these patients is required. Among patients receiving warfarin, the quality of anticoagulation care warrants improvement.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Homes for the Aged; Humans; Male; Nursing Homes; Prevalence; Treatment Outcome; Warfarin

Topics: Cerebrovascular Disorders; Follow-Up Studies; Health Status Indicators; Humans; Medicare; Mississippi; Thrombophlebitis; Tomography, X-Ray Computed; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Risk Factors; Warfarin

The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial.. Medical records of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation.. Mean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy.. Antithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Echocardiography; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hospitals, University; Humans; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Thromboembolism; United States; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Malpractice; Office Visits; Warfarin

We describe a case of pulmonary embolism and ischemic stroke due to paradoxical embolism in a healthy young woman taking oral contraceptives to treat an ovarian cyst. It was not possible to identify the site of the thromboembolus. Ultrasound techniques played an important role in identifying the peripheral arterial obstructions and in diagnosing acute pulmonary hypertension. Transesophageal echocardiography provided detailed information on both the morphology and the evolution of the atrial thrombus straddling the foramen ovale within the aneurysmal interatrial septum. The patient was given anticoagulant treatment, initially with heparin and subsequently with warfarin over a period of six months. Repeated ultrasound controls showed no thrombus, regression of the signs of pulmonary hypertension and, lastly unchanged systemic arterial obstruction.

Topics: Adult; Anticoagulants; Cerebrovascular Disorders; Contraceptives, Oral, Hormonal; Female; Heparin; Humans; Ovarian Cysts; Pulmonary Embolism; Thromboembolism; Ultrasonography; Warfarin

The prevalence of atrial fibrillation (AF) increases dramatically with advancing patient age, and, as a result, this condition is common in persons residing in the long-term care setting.. To assess the knowledge and attitudes of physicians regarding the use of warfarin for stroke prevention in patients with atrial fibrillation in long-term care facilities.. We surveyed physicians actively providing primary care to older patients in 30 long-term care facilities located in New England, Quebec, and Ontario. Physicians were requested to complete a structured questionnaire about use of warfarin therapy for stroke prevention in patients with AF residing in long-term care facilities. The questionnaire included two clinical scenarios designed to provide substantial contrasts in patient characteristics including underlying comorbidity, functional status, bleeding risk, and stroke risk.. A total of 269 physicians were asked to participate in the survey, and 182 (67.7%) completed the questionnaire between February 1, 1995, and July 31, 1995. Only 47% of respondents indicated that the benefits of warfarin therapy "greatly outweigh the risks" in this setting; the remainder of physicians indicated that benefits only "slightly outweigh the risks" (34%) or that risks "outweigh benefits" (19%). The most frequently cited contraindications to warfarin use were: excessive risk of falls (71%), history of gastrointestinal bleeding (71%), history of other non-central nervous system bleeding (36%), and history of cerebrovascular hemorrhage (25%). Among the 164 physicians who reported using the international normalized ratio to monitor warfarin therapy, 27% indicated a target range with a lower limit less than 2, 71% indicated a target range between 2 and 3, and 2% indicated an upper limit greater than 3. Among respondents who answered questions about the two clinical scenarios, estimates of the risk of a stroke without warfarin therapy and the risk of an intracranial hemorrhage with therapy varied widely.. Our findings suggest that many uncertainties surround the decision to prescribe warfarin to patients with AF in the long-term care setting, as well as questions about the appropriate intensity of this treatment when it is prescribed. Concerns about the risks of bleeding appear to prevail over stroke prevention when physicians make such prescribing decisions.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Health Knowledge, Attitudes, Practice; Humans; Long-Term Care; Male; New England; Ontario; Physicians; Quebec; Skilled Nursing Facilities; Surveys and Questionnaires; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cerebrovascular Disorders; Humans; Middle Aged; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Quality Control; United States; 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

Warfarin reduces the rate of stroke among patients with atrial fibrillation. We sought to determine warfarin use within a population sample of elderly patients with atrial fibrillation.. The Connecticut Peer Review Organization conducted a chart review of Medicare patients aged > or = 65 years with a history of atrial fibrillation before a hospitalization during the first 6 months of 1994.. Among 488 patients (308 women; 457 white; 173 aged > or = 85 years), 38% (184/488) had a relative contraindication to anticoagulation (history of bleeding, dementia, alcohol use, falls, cancer, or the need for nonsteroidal anti-inflammatory drugs). Among the remaining patients (with known atrial fibrillation, but without a contraindication), only 38% (117/304) had been prescribed warfarin. Of those not prescribed warfarin, 63% (117/187) were also not taking aspirin. There were 272 patients with at least one additional vascular risk factor and no contraindication to anticoagulation. Among these patients at moderate to high risk for stroke, anticoagulation had been prescribed in 40% (109/272). Overal, among those not prescribed warfarin, 58% (95/163) were not taking aspirin. Patients admitted with a stroke were more likely to be significantly underanticoagulated (with international normalized ratio < 1.5) (43.5% versus 20.9% for those without stroke; P < .005). Anticoagulation was most effective for those with an international normalized ratio > or = 2.0.. Warfarin anticoagulation with atrial fibrillation, even among "ideal" candidates, appears dramatically underutilized. In addition, among those prescribed warfarin, patients are often undertreated. Increased warfarin use among patients with atrial fibrillation represents an excellent opportunity for stroke prevention in the elderly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cohort Studies; Drug Utilization; Female; Humans; Male; Medical Records; Risk Factors; 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

Stroke is one of the most significant potential complications in patients who are undergoing cardioversion for atrial fibrillation. To minimize the risk of stroke, the American College of Chest Physicians' (ACCP's) Third Consensus Conference on Antithrombotic Therapy developed specific recommendations regarding anticoagulation before and following elective cardioversion of patients with atrial fibrillation.. To determine if patients undergoing cardioversion for atrial fibrillation are administered anticoagulants according to the ACCP's Third Consensus Conference on Antithrombotic Therapy recommendations.. A retrospective review of cases of atrial fibrillation at a tertiary care teaching hospital to determine if physicians are routinely following these recommendations.. Data were collected for the year 1994 for all patients admitted to a tertiary care teaching hospital with a diagnosis of atrial fibrillation (n = 111). The ACCP's recommendations that were evaluated included the following: patients undergoing elective cardioversion for atrial fibrillation should receive anticoagulation for 3 weeks before and 4 weeks following cardioversion except in cases of new-onset atrial fibrillation, and warfarin and heparin should be administered jointly for several days before discontinuation of heparin therapy.. Of the 111 patients who presented with a diagnosis of atrial fibrillation, 51 underwent elective cardioversion. In 18 (35%) of 51 cases, physicians failed to follow at least one of ACCP's recommendations regarding anticoagulation. These included failing to (1) administer anticoagulants to patients for 3 weeks before elective cardioversion (n = 14); (2) administer anticoagulants to patients for 4 weeks following cardioversion (n = 6); and (3) overlap heparin and/or warfarin therapies for 72 hours (n = 4). Six cases failed to meet more than one of these recommendations.. Physicians are not routinely following the ACCP's Third Consensus Conference on Antithrombotic Therapy recommendations regarding anticoagulation in elective cardioversion of atrial fibrillation, thus increasing patients' risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Echocardiography, Transesophageal; Electric Countershock; Female; Heparin; Humans; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Cost-Benefit Analysis; Humans; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Platelet Aggregation Inhibitors; Risk Factors; Warfarin

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Intracranial Embolism and Thrombosis; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Cerebrovascular Disorders; Embolism, Cholesterol; Humans; Male; Warfarin

To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case-control study.. We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin. For each patient with stroke, three controls with nonrheumatic atrial fibrillation who were treated as outpatients were randomly selected from the 1994 registry of the anticoagulant-therapy unit (222 controls). We used the international normalized ratio (INR) to measure the intensity of anticoagulation. For the patients with stroke, we used INR at admission; for the controls, we selected the INR that was measured closest to the month and day of the matched case patient's hospital admission.. The risk of stroke rose steeply at INRs below 2.0. At an INR of 1.7, the adjusted odds ratio for stroke, as compared with the risk at an INR of 2.0, was 2.0 (95 percent confidence interval, 1.6 to 2.4); at an INR of 1.5, it was 3.3 (95 percent confidence interval, 2.4 to 4.6); and at an INR of 1.3, it was 6.0 (95 percent confidence interval, 3.6 to 9.8). Other independent risk factors were previous stroke (odds ratio, 10.4; 95 percent confidence interval, 4.4 to 24.5), diabetes mellitus (odds ratio, 2.95; 95 percent confidence interval, 1.3 to 6.5), hypertension (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 5.7), and current smoking (odds ratio, 5.7; 95 percent confidence interval, 1.4 to 24.0).. Among patients with atrial fibrillation, anticoagulant prophylaxis is effective at INRs of 2.0 or greater. Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0, tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower, less effective levels of anticoagulation.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Odds Ratio; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Humans; Warfarin

A subject with dissection of the internal carotid artery (ICA) may present with a variety of symptoms, from headache to stroke. Thus far, it has not been possible to identify the subset of patients at risk for cerebral ischemia. Because the majority of these ischemic events are secondary to embolic phenomena, we used transcranial Doppler (TCD) evaluation with emboli monitoring to study 17 consecutive patients with ICA dissection treated at Harborview Medical Center, Seattle, Wash, during a 2-year period from 1992 until 1994.. Ten patients with ICA dissection secondary to trauma and seven with spontaneous ICA dissection were diagnosed by carotid angiography and studied by TCD from the time of diagnosis through initiation of therapy. Emboli monitoring was performed in the middle cerebral artery (MCA) ipsilateral to the dissection at the initial evaluation and intermittently thereafter to ensure that the emboli stopped with treatment.. Emboli were detected in the MCA distal to the dissection in 10 of 17 patients (59%). Patients with microemboli detected by TCD presented with a stroke (70%) much more frequently than those without emboli (14%) (P=.0498). The presence of a pseudoaneurysm did not increase the risk of either microemboli or stroke.. We have demonstrated a high incidence of intracranial microemboli in the MCA distal to carotid dissections and a significant correlation between the presence of emboli and stroke. TCD can therefore be used as an adjunctive tool to manage patients with suspected carotid dissection and may prove useful in evaluating the efficacy of treatment in reducing microemboli and subsequent stroke.

Topics: Adolescent; Adult; Anticoagulants; Aortic Dissection; Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Angiography; Cerebral Arteries; Cerebrovascular Disorders; Child; Female; Heparin; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Ultrasonography, Doppler, Transcranial; Warfarin; Washington

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

The incident Monitoring in General Practice Project began as an initiative of the Professional Indemnity Review. Anonymous data from general practitioners about unintended, and possibly adverse events were collected in order to develop preventive strategies that might ultimately increase patient safety and therefore reduce litigation. Feedback and sharing of experiences and ideas about these events, possible management strategies or the project as a whole are invited from the readers.

Topics: Anticoagulants; Australia; Cerebrovascular Disorders; Communication; Family Practice; Humans; Malpractice; Patient Education as Topic; Physician-Patient Relations; Referral and Consultation; 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

Atrial fibrillation (AF) is an important and independent risk factor for stroke, particularly in elderly people. The efficacy of treatment with warfarin and aspirin in primary and secondary stroke prevention in AF has been demonstrated in randomized clinical trials. In a demographic study, we examined the prevalence of AF in patients registered with a general practice in the North East of England; 91 patients with known AF were identified, 69 with chronic AF and 22 with paroxysmal AF. The mean duration of the arrhythmia was 6.43 years and the prevalence of AF increased with age. There was a high prevalence of cerebrovascular disease in AF patients. The majority of AF patients were not receiving therapy with aspirin or warfarin as primary or secondary stroke prevention. If strategies for stroke prevention in AF are to be applied to the community, general practitioners will need to play a more active part.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Cross-Sectional Studies; England; Female; Geriatric Assessment; Humans; Incidence; Male; Platelet Aggregation Inhibitors; Primary Health Care; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Peer Review; Pennsylvania; Quality Assurance, Health Care; Warfarin

The risk of stroke in patients with atrial fibrillation can be significantly reduced with antithrombotic therapy. Despite this, many physicians remain hesitant to prescribe warfarin sodium or aspirin therapy for patients with atrial fibrillation.. To assess the use of antithrombotic therapy in patients with atrial fibrillation at 6 academic hospitals in the United States.. Records were reviewed from consecutive hospital admissions of 309 patients with atrial fibrillation at 6 members of the University Health System Consortium, Oak Brook, III, which is a member driven alliance of 70 academic health centers in the United States. Risk factors for stroke, contraindications to anticoagulant therapy, and use of antithrombotic therapy at admission and discharge were recorded.. The mean age of patients was 71.6 years, 54% had chronic, 22% paroxysmal, and 24% new-onset atrial fibrillation. Eighty-two percent of the patients had cardiovascular risk factors that have been associated with increased risk of stroke. At least 1 relative contraindication to anticoagulant therapy was present in 44%. At the time of admission. 32% of the patients with previously diagnosed atrial fibrillation (n = 235) were receiving warfarin (or warfarin plus aspirin), 31% were receiving aspirin alone, and 36% were receiving no antithrombotic therapy. At discharge (n = 230), 41% of these patients were taking warfarin (or warfarin plus aspirin) and 36% were taking aspirin. Forty-four percent of the patients with risk factors for stroke and no contraindications to anticoagulation (n = 134) were discharged on a regimen of warfarin (or warfarin plus aspirin), 34% were discharged on a regimen of aspirin, and 22% received no antithrombotic therapy.. About half of the patients with atrial fibrillation admitted to these academic hospitals had clinical risk factors that are associated with increased risk of stroke and no contraindications to anticoagulation. Antithrombotic therapy was underused in these patients.

Topics: Academic Medical Centers; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Utilization Review; Female; Fibrinolytic Agents; Humans; Male; Medical Audit; Middle Aged; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Risk Factors; United States; Warfarin

Common indices for the quantal assessment of treatment efficacy are reviewed. The absolute risk reduction is a practical index for public health considerations. Its reciprocal has been termed the 'Number Needed to Treat' (NNT), representing the health effort that must on average be expended to accomplish one tangible treatment target. We extend the NNT to evaluate outcome combinations of treatment benefits versus treatment harms.. We describe the mathematical context of the NNT, and extend it to evaluate outcome combinations (treatment success/failure with/without treatment-induced adverse effects) in a treated population. These extensions are carried out assuming either independence or positive association between treatment benefit and treatment harm. A method is provided for calculating the standard errors of these extended NNT values. Applications to cost-effectiveness analysis are discussed.. We calculate NNT in three recent therapeutic studies. The results of a trial of the prevention of strokes with warfarin in patients with non-valvular atrial fibrillation are analysed to evaluate treatment success (stroke prevention) against treatment-induced bleeds. An NNT-related cost-benefit analysis is also carried out. We also analyse the results of a study of two modalities of chemotherapeutic treatment in small-cell lung cancer, and of two modalities of surgical intervention in the treatment of cholelithiasis.. The NNT are useful in direct evaluation of outcome-specific treatment benefits versus treatment-induced harms. They may also be used in cost-effectiveness analyses and are helpful in guiding public health programmes towards the identification of optimal treatment strategies.

Topics: Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Carcinoma, Small Cell; Cerebral Hemorrhage; Cerebrovascular Disorders; Cholecystectomy; Clinical Protocols; Cost-Benefit Analysis; Decision Support Techniques; Evaluation Studies as Topic; Health Care Costs; Humans; Models, Theoretical; Postoperative Complications; Quality-Adjusted Life Years; Sweden; Therapeutics; Treatment Failure; Treatment Outcome; Warfarin

To determine how often warfarin was prescribed to patients with nonrheumatic atrial fibrillation in our community in 1992 when randomized trials had demonstrated that warfarin could prevent stroke with little increase in the rate of hemorrhage, and to determine whether warfarin was prescribed less frequently to older patients-the patients at highest risk of stroke but of most concern to physicians in terms of the safety of warfarin.. Cross-sectional study. Appropriateness of warfarin was classified for each patient based on the independent judgments of three physicians applying relevant evidence and guidelines.. Two teaching hospitals and five community-based practices.. Consecutive patients with nonrheumatic atrial fibrillation (n = 189).. Warfarin was prescribed to 44 (23%) of the 189 patients. Warfarin was judged appropriate in 98 patients (52%), of whom 36 (37%) were prescribed warfarin. Warfarin was prescribed to 11 (14%) of 76 patients aged 75 years or older with hypertension, diabetes mellitus, or past stroke, the group at highest risk of stroke. In a multivariable logistic regression model controlling for appropriateness of warfarin and other patient characteristics, patients aged 75 years or older were less likely than younger patients to be treated with warfarin (odds ratio 0.25; 95% confidence interval 0.10, 0.65).. Warfarin was prescribed infrequently to these patients with nonrheumatic atrial fibrillation, especially the older patients and even the patients for whom warfarin was judged appropriate. These findings indicate a substantial opportunity to prevent stroke.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cross-Sectional Studies; Drug Utilization; Drug Utilization Review; Female; Humans; Logistic Models; Male; Middle Aged; Ohio; Peer Review, Health Care; Practice Patterns, Physicians'; Quality of Health Care; Risk Factors; Warfarin

To determine the opinions of selected physicians in our community about use of warfarin for patients with nonrheumatic atrial fibrillation, and to determine the relation of the physicians' opinions to their practices.. Survey of physicians, using eight hypothetical clinical vignettes to characterize physicians' opinions about use of warfarin in patients with nonrheumatic atrial fibrillation, according to patient age, risk of bleeding, and risk of stroke.. Two teaching hospitals and five community-based practices.. Eighty physicians who cared for 189 consecutive patients with nonrheumatic atrial fibrillation.. The survey response rate was 73%. Nearly all responding physicians (90%) recommended warfarin for at least one vignette. However, physicians recommended warfarin less often for vignettes depicting 85-year-old patients than for matched vignettes depicting 65-year-old patients (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.01, 0.08), and less often for cases with specified risk factors for bleeding than for matched cases without the risk factors (OR 0.01; 95% CI 0.004, 0.03); warfarin was recommended more often for cases with a recent stroke than for matched cases without this history (OR 8.2; 95% CI 3.6, 18). In practice, warfarin was prescribed more often (p < or = .05) by physicians reporting good personal experience and by those who had favorable opinions about its use. However, even physicians with good experience and favorable opinions did not prescribe warfarin to half of their patents for whom warfarin was independently judged appropriate.. Physicians' opinions frequently opposed warfarin for older patients with nonrheumatic atrial fibrillation, and for those with bleeding risk factors. Physicians' opinions, as well as other barriers to warfarin therapy, most likely contribute to its infrequent prescription.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Attitude of Health Personnel; Cerebrovascular Disorders; Cross-Sectional Studies; Drug Utilization Review; Female; Health Care Surveys; Health Knowledge, Attitudes, Practice; Humans; Logistic Models; Male; Middle Aged; Practice Patterns, Physicians'; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Attitude of Health Personnel; Cerebrovascular Disorders; Drug Utilization; Health Knowledge, Attitudes, Practice; Humans; Practice Patterns, Physicians'; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Humans; Middle Aged; Risk Factors; Warfarin

To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation (NVAF) with or without additional stroke risk factors (a prior stroke or transient ischemic attack, diabetes, hypertension, or heart disease).. Decision and cost-effectiveness analyses. The probabilities for stroke, hemorrhage, and death were obtained from published randomized controlled trials. The quality-of-life estimates were obtained by interviewing 74 patients with atrial fibrillation. Costs were estimated from literature review, phone survey, and Medicare reimbursement.. In the base case, the patients were 65 years of age and good candidates for warfarin therapy.. Treatment with warfarin, aspirin, or no therapy in the decision analytic model.. Quality-adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy.. For patients with NVAF and additional risk factors for stroke, warfarin therapy led to a greater quality-adjusted survival and to cost savings. For patients with NVAF and one additional risk factor, warfarin therapy cost $8000 per quality-adjusted life-year saved. For 65-year-old patients with NVAF alone, warfarin cost about $370,000 per quality-adjusted life-year saved, as compared with aspirin therapy. However, for 75-year-old patients with NVAF alone, prescribing warfarin cost $110,000 per quality-adjusted life-year saved. For patients who were not prescribed warfarin, aspirin was preferred to no therapy on the basis of both quality-adjusted survival and cost in all patients, regardless of the number of risk factors present.. Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke. In 65-year-old patients with NVAF but no other risk factors for stroke, prescribing warfarin instead of aspirin would affect quality-adjusted survival minimally but increase costs significantly.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; California; Cerebrovascular Disorders; Cost-Benefit Analysis; Decision Support Techniques; Hemorrhage; Humans; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Treatment Outcome; Warfarin

Topics: Aged; Cerebrovascular Disorders; Humans; Middle Aged; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Cerebrovascular Disorders; Humans; Thrombolytic Therapy; Warfarin

Topics: Aspirin; Cerebrovascular Disorders; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Societies, Medical; Ticlopidine; United States; 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

Stroke is largely a preventable disease. However, there are little data available concerning the use of stroke prevention diagnostic and treatment modalities by practicing physicians. These data are critical for the rational allocation of resources and targeting of educational efforts. The purposes of this national survey were to gather information about physicians' stroke prevention practice patterns and their attitudes and beliefs regarding secondary and tertiary stroke prevention strategies.. We conducted a national survey of stroke prevention practices among a stratified random sample of 2000 physicians drawn from the American Medical Association's Physician Masterfile. The survey focused on the availability of services and the use of diagnostic and preventive strategies for patients at elevated risk of stroke.. Sixty-seven percent (n = 1006) of eligible physicians completed the survey. Diagnostic studies considered readily available by at least 90% of physicians included carotid ultrasonography, transthoracic echocardiography, Holter monitoring, and brain CT and MRI scans. MR angiography was perceived as being readily available by 68% and transesophageal echocardiography by 74% of respondents. Twelve percent of physicians reported cerebral arteriography and 10% reported carotid endarterectomy as not being readily available. Multiple logistic regression analyses showed that the availability of services varied with physician specialty (noninternist primary care, internal medicine, neurology, surgery), practice setting (nonmetropolitan versus small metropolitan or large metropolitan areas), and for carotid endarterectomy, region of the country (South, Central, Northeast, and West). The odds of carotid endarterectomy being reported as readily available were approximately 2.5 to 3.5 times greater for physicians practicing in the central, northeastern, and western regions compared with those practicing in the South, independent of practice setting and specialty. With regard to stroke prevention practices, 61% of physicians reported prescribing 325 mg of aspirin for stroke prevention, while 33% recommend less than 325 mg and 4% use doses of 650 mg or more. Seventy-one percent of physicians using warfarin reported monitoring anticoagulation with international normalized ratios, and 78% reported monitoring anticoagulated patients at least once a month. Fewer than 20% of physicians reported knowing the perioperative carotid endarterectomy complication rates at the hospital where they perform the operation themselves or refer patients to have the procedure done.. Although all routine and most specialized services for secondary and tertiary stroke prevention are readily available to most physicians, variation in availability exists. The use of international normalized ratios for monitoring warfarin therapy has not yet become universal. Physician knowledge of carotid endarterectomy complication rates is generally lacking. Depending on their causes, these problems may be addressed through targeted physician education efforts and systematic changes in the way in which services are provided.

Topics: Aspirin; Attitude of Health Personnel; Brain Ischemia; Carotid Arteries; Cerebral Angiography; Cerebrovascular Disorders; Echocardiography; Echocardiography, Transesophageal; Education, Medical, Continuing; Electrocardiography, Ambulatory; Endarterectomy, Carotid; Health Care Rationing; Health Services Accessibility; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Middle Aged; Physicians; Practice Patterns, Physicians'; Professional Practice; Risk Factors; Tomography, X-Ray Computed; United States; Warfarin

Several studies have demonstrated an association between mitral annular calcification and stroke; however, the pathophysiological explanation remains speculative.. We describe two patients with cerebral embolism in whom mitral valve calcification was demonstrated by transthoracic echocardiography. In both patients, transesophageal echocardiography identified a mass that appeared to be thrombus on the calcified portion of the mitral apparatus. There was no evidence of a hypercoagulable state or endocarditis in either case. Repeated transesophageal echocardiography after anticoagulation demonstrated resolution of the masses in both patients.. These cases support the hypothesis that thrombus formation may be a pathophysiological link between ischemic cerebral events and mitral annular calcification in some patients.

Topics: Aged; Brain Ischemia; Calcinosis; Cerebral Infarction; Cerebrovascular Disorders; Echocardiography; Echocardiography, Transesophageal; Female; Heart Valve Diseases; Humans; Intracranial Embolism and Thrombosis; Middle Aged; Mitral Valve; Thrombosis; Warfarin

Several large trials have shown that the risk of stroke in patients with non-valvar atrial fibrillation is reduced by treatment with warfarin. Implementing this research evidence requires not only an understanding of the trials' results and of the changes that they imply for clinicians' treatment decisions but also an appreciation of the organisation, quantity, and quality of services required to support these changes. Understanding of these implications is crucial for developing services that allow changes in practice to produce reductions in stroke incidence while minimising the risks of treatment. This article considers the developments in service provision that will probably be required to support the changes in clinical practice suggested by the trials' results. These services will be provided largely by doctors, and their development has implications for doctors in both primary and secondary care.

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Cost-Benefit Analysis; Health Services Needs and Demand; Humans; Patient Selection; Practice Patterns, Physicians'; Quality of Health Care; United Kingdom; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Hemorrhage; Humans; Warfarin

Topics: Cerebrovascular Disorders; Heart Aneurysm; Humans; Male; Middle Aged; Neurologic Examination; Thromboembolism; Tomography, X-Ray Computed; Warfarin

We aimed to examine the effect of age upon the control of anticoagulation with warfarin in ordinary clinical practice, using a retrospective examination of routine anticoagulation clinic records from the University Hospital, Nottingham. Considerable over-anticoagulation (international normalisation ratio (INR) > 6.0) during induction occurred in 54 (11%) of 495 patients and was more likely in older patients (p < 0.05). Lesser degrees of over-anticoagulation during induction (INR > 4.0) were also more common in older patients, occurring in 58% of those aged 75 or above. Loading doses of warfarin were not reduced in older patients. INR in the maintenance phase rose with age (p < 0.001) despite lower maintenance doses of warfarin (p < 0.001). An INR > 6.0 in the maintenance phase was noted in 24 (3%) of 739 patients and again was more likely in older patients (p < 0.05). Patients using ambulance transport to the clinic were older than those who did not (p < 0.01) and those aged over 75 had shorter intervals between clinic visits (p < 0.01). We conclude that doctors using warfarin therapy do not take sufficient account of the increased sensitivity of older people to warfarin. Hospital anticoagulant policies need implementation and evaluation.

Topics: Age Factors; Aged; Cerebrovascular Disorders; Cross-Sectional Studies; Drug Administration Schedule; Humans; Longitudinal Studies; Middle Aged; Outpatient Clinics, Hospital; Warfarin

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

Thromboembolic phenomena involving the caval veins, right atrium, and pulmonary artery are recognised complications after the Fontan operation and other forms of total cavopulmonary connection. A rare case of systemic thromboembolism is reported in a 3 year old girl who had repeated coronary and cerebral thromboembolic events after a fenestrated total cavopulmonary shunt operation. A survey of the 18 paediatric cardiac units in the United Kingdom and Ireland showed a wide discrepancy in anticoagulation policies after Fontan-type operations. Prevention of thrombotic complications by lifelong postoperative anticoagulation may outweigh the risk of haemorrhage.

Topics: Aspirin; Cerebrovascular Disorders; Child, Preschool; Drug Administration Schedule; Female; Fontan Procedure; Humans; Myocardial Infarction; Postoperative Complications; Thromboembolism; Warfarin

Cardioversion of atrial fibrillation carries a serious risk of major thromboembolism and stroke. To determine whether or not the procedure alters plasma levels of fibrin D-dimer (a marker of intravascular fibrin turnover and thrombus formation) and plasma fibrinogen (associated with stroke and thromboembolism), we performed a prospective study in 19 patients with atrial fibrillation in whom cardioversion was attempted: seven patients without prior oral anticoagulant therapy (but with intravenous heparin for 24 h) (Group I), and 12 patients with full oral anticoagulation pre- and post-cardioversion (Group II). Plasma fibrinogen and fibrin D-dimer were measured pre-cardioversion, and at Days 3, 7 and 14 post-cardioversion. In Group I, there was a significant reduction in median plasma fibrin D-dimer levels by 14 days following cardioversion (200 vs. 52 ng/ml; paired Wilcoxon test, P = 0.02). In Group II, there was no change in median plasma fibrin D-dimer levels over the 14 days following cardioversion. There were no significant changes in plasma fibrinogen with cardioversion in either group of patients. The reduction of plasma fibrin D-dimer in Group I suggests a beneficial reduction of intravascular fibrin turnover and thrombogenesis by the cardioversion of patients with atrial fibrillation to sinus rhythm. Furthermore, it strongly suggests that it is atrial fibrillation itself which is the major risk of thromboembolism and that the risk continues for up to 14 days post-cardioversion. In Group II, the low pre-cardioversion fibrin D-dimer levels and lack of change with cardioversion is consistent with the prophylactic effect of warfarin therapy against thromboembolism during the cardioversion of atrial fibrillation.

Topics: Adult; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Cerebrovascular Disorders; Electric Countershock; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Follow-Up Studies; Heart Rate; Heparin; Humans; Male; Middle Aged; Prospective Studies; Thromboembolism; Warfarin

All patients (285) undergoing mitral valve replacement (MVR) with a Carpentier-Edwards (C-E) bioprosthesis +/- coronary bypass grafts (CABG) were reviewed (109 men and 176 women with a median age of 70 years). Overall, the 5-year survival rate was 58.9%, 62.7% for MVR (199 patients) and 50.1% for MVR+CABG (86 patients). Late survival was adversely affected by the operative time variables of NYHA class IV, older (> or = 70 years) age, low (> or = 56%) ejection fraction (EF), and the additional performance of associated procedures+CABG with MVR (P < or = 0.001). The 5-year freedom from stroke rate was 89.2%, 89.1% for MVR and 90.2% for MVR +/- CABG. Advanced heart class was the only significant variable associated with a greater risk of late stroke (P < or = 0.01). Neither chronic preoperative atrial fibrillation nor operative obliteration of the left atrial appendage increased or decreased the late risk of stroke in patients following MVR. Hazard function for stroke occurring in the first postoperative year (first 48 h excluded to discount intraoperative events) demonstrated the highest rate within the first month (40%), rapidly diminishing thereafter. This pattern was reproduced in the 12-year hazard function in that the rate of stroke occurrence was greatest in the first year (6.7%) following implantation. The mean stroke rate over 12 years was 2.5%. Strokes following MVR +/- CABG are more likely to occur in older and more compromised patients, and the higher early rate is not reflected in the mean rate. A more aggressive approach to early anticoagulation with IV heparin, Coumadin, and possibly antiplatelet therapy is advocated to reduce this complication rate.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Cerebrovascular Disorders; Child; Child, Preschool; Chronic Disease; Cohort Studies; Coronary Artery Bypass; Disease-Free Survival; Female; Follow-Up Studies; Heart Diseases; Heart Valve Prosthesis; Heparin; Humans; Intraoperative Complications; Male; Middle Aged; Mitral Valve; Platelet Aggregation Inhibitors; Postoperative Complications; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke Volume; Survival Rate; 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

A simplified method for direct determination of warfarin enantiomers by high-pressure liquid chromatography with fluorescence detection has been developed. This method involves solid phase extraction of warfarin in plasma, precolumn derivatization to form diastereoisomeric esters, and post-column reaction to discriminate each enantiomer separately. Ultrafiltration was employed in the separation of unbound warfarin enantiomers. Twelve plasma samples from six stroke patients taking warfarin regularly were analyzed. The average concentration of total warfarin was 0.47 +/- 0.17 mg/L for the S-isomer and 0.69 +/- 0.18 mg/L for the R-isomer. The average protein binding was 99.67 +/- 0.33% for S-warfarin and 99.44 +/- 0.33% for R-warfarin. This methodology provides a quick and reliable technique for determining enantiomeric protein binding of warfarin in clinical settings.

Topics: Aged; Blood Proteins; Calibration; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Fluorescence; Humans; Male; Middle Aged; Protein Binding; Stereoisomerism; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Warfarin

Topics: Aged; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Incidence; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Prothrombin Time; Risk Factors; Warfarin

Topics: Administration, Oral; American Heart Association; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Drug Interactions; Female; Heart Valve Diseases; Humans; Male; Myocardial Infarction; Pregnancy; Thromboembolism; Warfarin

Paradoxical embolism through a patent foramen ovale is a recognized cause of stroke, but clinical predictors, recurrence rate, and prevention of brain infarcts in patients with patent foramen ovale have not been determined. We reviewed transesophageal echocardiographic records to ascertain echocardiographic predictors and optimal prophylaxis for patent foramen ovale-related infarcts.. A patent foramen ovale was identified in 74 patients during 615 transesophageal echocardiograms by color Doppler or saline contrast during a 60-month period. On the basis of final clinical situation, the patients were divided into the following groups: group 1, infarct with patent foramen ovale a likely cause (n = 16); group 2, infarct with patent foramen ovale an unlikely cause (n = 23); and group 3, no infarct (n = 35). Transesophageal echocardiograms were reviewed to assess patent foramen ovale characteristics and associated cardio-embolic sources without knowledge of clinical details or group assignment. Follow-up after a patent foramen ovale-related infarct was obtained by telephone or written correspondence in 15 of 16 group 1 patients.. Atrial septal aneurysms were more common in group 1 (38%) compared with group 2 (10%) and group 3 (8%) (P = .02). Contrast right-to-left shunting occurred in 88% of group 1 (P = .06) and 86% of group 2 (P = .07) compared with 60% of group 3. Prevention of recurrence in subjects with presumed patent foramen ovale-related brain infarcts varied. Aspirin was usually chosen after initial brain ischemia. Warfarin and patent foramen ovale closure were usually reserved for subjects with symptoms of brain ischemia while taking aspirin or those who required warfarin or cardiac surgery for other indications. No recurrent infarcts occurred in 15 patients during a mean follow-up period of 28 months.. Atrial septal aneurysm and right-to-left shunt may be predictive of a patent foramen ovale that predisposes a patient to stroke. Aspirin may provide sufficient infarct prophylaxis after initial ischemia. Warfarin and surgical correction should likely be reserved for those in whom aspirin is not effective or those who require warfarin or cardiac surgery for other reasons until prospective studies are available.

Topics: Adult; Aged; Aspirin; Cerebral Infarction; Cerebrovascular Disorders; Echocardiography, Transesophageal; Embolism; Female; Heart Aneurysm; Heart Diseases; Heart Septal Defects, Atrial; Heart Septum; Humans; Male; Middle Aged; Recurrence; 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

To report a case of suboptimal warfarin monitoring.. A patient with a history of rheumatic heart disease and a mechanical mitral valve was admitted to the local hospital complaining of left-sided weakness. At the time, she was receiving warfarin 5 mg/d. Upon admission her prothrombin time (PT) was 15 s. An initial computed tomography (CT) scan of the head was negative. On the basis of the initial findings, it was unclear whether the symptoms were caused by a cerebrovascular accident (CVA). The patient was transferred to the University Medical Center for a more thorough evaluation. The diagnosis of CVA was confirmed by a repeat CT scan seven days after the event. On the basis of the information obtained from the local hospital, it was determined that the initial PT of 15 s converted to an International Normalized Ratio (INR) of 1.5, which is below the recommended range for patients with mechanical heart valves. Prior to discharge, the warfarin dosage was increased to obtain an INR in the recommended range of 2.5-3.5.. This case illustrates the problems that exist with the current system of PT reporting and the potential advantages of using the INR. Variations in the sensitivity of the thromboplastin reagents used to perform the PT may result in misinterpretation of the level of anticoagulation and errors in warfarin dosage adjustments. The potential for suboptimal anticoagulation is greatly increased in patients, such as the one reported here, who are having PTs performed by multiple laboratories.. To maximize efficacy and minimized the risk of bleeding complications, warfarin therapy must be individualized and closely monitored. Standardization of PT monitoring through the use of the INR would significantly reduce the potential for suboptimal anticoagulation associated with the traditional system of reporting.

Topics: Cerebrovascular Disorders; Drug Monitoring; Female; Heart Valve Prosthesis; Humans; Middle Aged; Prothrombin Time; Warfarin

Strokes are responsible for significant morbidity and mortality. Persons who have chronic atrial fibrillation are at higher risk of having a stroke. Previously, anticoagulation with warfarin was instituted only in persons with atrial fibrillation associated with valvular problems. More recently, five studies have shown a clear benefit to using warfarin in persons with atrial fibrillation related to nonvalvular conditions, such as hypertension, coronary artery disease, and heart failure. Patients who were given warfarin in therapeutic dosages, as measured by prothrombin time ratios and International Normalized Ratios (INRs), had a significant reduction in stroke risk ranging from 37 to 79% in the five studies. The outcomes of these five studies have changed the way persons with chronic, nonvalvular atrial fibrillation are managed. Health care providers play a key role in the counseling of patients who are considering the use of warfarin, the patient education regarding potential complications and drug interactions, and the ongoing monitoring and laboratory testing needed for dosage adjustments.

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Drug Interactions; Drug Monitoring; Humans; Patient Compliance; Patient Education as Topic; Primary Prevention; Prothrombin Time; Risk Factors; Treatment Outcome; 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

Patients with non-rheumatic atrial fibrillation have a fivefold increased risk of stroke. Warfarin reduces this risk by approximately two thirds, but evidence for benefit from aspirin is less compelling. We assessed whether our current practice reflects the message of the trials. In a retrospective case record study we reviewed notes of 131 patients with atrial fibrillation (AF), mean age 79 (range 53-95) years, admitted to a medical unit (72) or geriatric assessment unit (59). Thirty-two patients had paroxysmal AF. Of 115 patients with nonrheumatic AF, 36 (31%) had one or more recorded contraindication to anti-coagulation. Although 79 patients (69%) had no recorded contraindication to warfarin, only 2 took warfarin and 15 aspirin prior to admission. Ten patients commenced warfarin and 8 aspirin before discharge. Thirty-nine patients (53%) without contraindication, were discharged without antithrombotic therapy. Despite evidence to support anticoagulating patients with non-rheumatic AF, this rarely occurs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Patient Discharge; Retrospective Studies; Scotland; Thrombolytic Therapy; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

Atrial fibrillation is the most common sustained cardiac arrhythmia encountered in clinical practice. Atrial fibrillation increases with age and is relatively common (> 5%) in patients > 69 years old. Despite this, our understanding of the underlying electrophysiologic mechanisms and the optimal management remains incomplete. This arrhythmia is seen most frequently in association with coronary disease or hypertension, but it is also frequently a consequence of rheumatic heart disease. The mechanism of atrial fibrillation requires further elucidation, but the most widely accepted hypothesis is a multiple reentrant wavelet mechanism. The treatment of atrial fibrillation is undertaken to reduce the risk of stroke or systemic embolus, to control palpitation or other symptoms or to improve exercise tolerance or treat pulmonary congestion. This report is a discussion of the epidemiology of atrial fibrillation and of the etiology, mechanism, management and future research directions in the study of this arrhythmia.

Topics: Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Heart Conduction System; Humans; Incidence; Intracranial Embolism and Thrombosis; National Institutes of Health (U.S.); United States; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chronic Disease; Humans; Thromboembolism; Warfarin

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Family Practice; Humans; Warfarin

Topics: Aged; Atrial Fibrillation; Attitude of Health Personnel; Cerebrovascular Disorders; Consultants; Humans; Physicians; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Female; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; 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

Topics: Aged; Carotid Arteries; Cerebrovascular Disorders; Endarterectomy; Epidemiologic Methods; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Risk Factors; Smoking; Survival Analysis; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Fibrinolytic Agents; Humans; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Risk Factors; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Family Practice; Health Promotion; Humans; Randomized Controlled Trials as Topic; Warfarin

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cerebrovascular Disorders; Contraindications; Humans; Risk Factors; Treatment Refusal; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

After reviewing these published studies, I think one can conclude that in the patient population with chronic and/or paroxysmal atrial fibrillation, warfarin is beneficial and the benefits outweigh the risks. However, it is important to point out that patients at high risk for embolic disease, for example, dilated cardiomyopathy patients, were rarely included in these trials. The five trials mentioned above do not address this patient population. Current opinion is that these individuals should receive anticoagulation despite the lack of objective evidence that anticoagulation is beneficial if the risk of bleeding is not excessive. The five trials also do not address the population of patients categorized as having "lone atrial fibrillation," that is, atrial fibrillation occurring in patients with no structural heart disease. The general consensus in the low embolic risk patient, (i.e., the patient < 60 years of age who has lone atrial fibrillation) is that the risk of anticoagulation is greater than the benefit. My final thought on the subject concerns the risk of pulmonary emboli in this patient population. My guess is that this group of patients is at high risk for small pulmonary emboli, which in many instances may be subclinical--for example, clots too small to result in persistent tachypnea or tachycardia. As far as I can tell, there are no randomized trials on the prevention of pulmonary emboli in patients with chronic or paroxysmal atrial fibrillation using anticoagulation or aspirin. I guess the systemic emboli trial data are sufficient to indicate a protective effect on the lungs as well as on the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Randomized Controlled Trials as Topic; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Randomized Controlled Trials as Topic; Therapeutic Human Experimentation; Warfarin

Ischemic strokes occurring in patients with nonrheumatic atrial fibrillation are due to a variety of mechanisms, not exclusively to cardiogenic embolism. Without knowledge of antithrombotic therapy assignment, we categorized strokes in the Stroke Prevention in Atrial Fibrillation Study as presumed cardioembolic or noncardioembolic. We then compared patient clinical and echocardiographic variables, as well as the efficacy of aspirin prophylaxis, for each stroke type. Of 71 ischemic strokes, we categorized 46 (65%) as cardioembolic, 13 (18%) as noncardioembolic, and 12 (17%) as of uncertain cause. Patients developing noncardioembolic strokes, relative to cardioembolic strokes, were more commonly men (p = 0.005) and were more likely to have left ventricular wall motion abnormalities by two-dimensional echocardiography (p = 0.002). Aspirin reduced the occurrence of strokes categorized as noncardioembolic significantly more than it did those categorized as cardioembolic (p = 0.01). These results emphasize the value of considering stroke mechanisms in therapeutic trials of antithrombotic agents and suggest a differential effect of aspirin according to mechanism.

Topics: Aged; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Male; Risk Factors; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Male; Sex Factors; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Humans; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Prothrombin Time; Warfarin

Topics: Age Factors; Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Humans; Risk Factors; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Humans; Risk Factors; Warfarin

Topics: Atrial Fibrillation; Cerebrovascular Disorders; Endarterectomy, Carotid; Humans; 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

To report two cases demonstrating an interaction between danazol and warfarin, resulting in the potentiation of warfarin's effect and bleeding complications.. Case reports, review articles, and studies identified by MEDLINE.. All published English-language reports involving danazol and warfarin interactions were reviewed.. Danazol, a synthetic testosterone derivative, is used in the treatment of endometriosis, fibrocystic breast disease, menorrhagia protein C deficiency, and hemophilia. We describe two cases including an interaction between danazol and warfarin, resulting in bleeding complications. There are at least two other reported cases of this interaction. This interaction may be attributable to several mechanisms. Danazol may inhibit the metabolism of warfarin and/or it may have a direct effect on the coagulation and fibrinolytic systems.. Based on this report and other published cases, clinicians must be aware that danazol may increase the anticoagulant effect of warfarin. Patients receiving warfarin who are prescribed danazol must be monitored closely to prevent excessive anticoagulation and subsequent bleeding. Studies are needed to determine the frequency of this interaction and its underlying mechanisms.

Topics: Adult; Cerebrovascular Disorders; Danazol; Drug Synergism; Female; Humans; Middle Aged; Prothrombin Time; Warfarin

Topics: Atrial Fibrillation; Case-Control Studies; Cerebrovascular Disorders; Humans; Risk Factors; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Middle Aged; Randomized Controlled Trials as Topic; Warfarin

Topics: Acute Disease; Acyclovir; Administration, Oral; Antibodies, Viral; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Embolism; Humans; Immunoassay; Infectious Mononucleosis; National Institutes of Health (U.S.); Simplexvirus; United States; Warfarin

Topics: Aged; Aspirin; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Recurrence; Warfarin

Topics: Aspirin; Cerebrovascular Disorders; Humans; Recurrence; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Humans; Research Design; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Dipyridamole; Embolism; Humans; Warfarin

The use of oral anticoagulants and antiplatelet agents for the prevention of strokes in elderly patients with atrial fibrillation is controversial. Recent studies suggest that warfarin and aspirin can be safe and effective in selected patients. To determine attitudes toward this subject, we sent a questionnaire to 480 attending physicians at two major university-affiliated medical centers. Among the 251 responses (52.3%), 46 respondents (18.3%) used warfarin in atrial fibrillation of any cause, 175 (69.7%) used it in atrial fibrillation with transient ischemic attacks, 161 (64.1%) used it in patients with cerebrovascular accidents, and 196 (78.0%) used it in patients with mitral valve disease. One hundred twenty-nine (51.4%) believed that the risk of hemorrhage associated with warfarin outweighs the benefit, 61 (24.3%) were not convinced that warfarin prevents strokes in atrial fibrillation, and 42 (16.7%) believed it was difficult to monitor prothrombin time in the elderly because of poor compliance. Aspirin was used by 91 physicians (36.2%) in atrial fibrillation of any cause, 161 (64.1%) in patients with transient ischemic attacks, 140 (55.7%) in patients with cerebrovascular accidents, and 48 (19.1%) when patients were in sinus rhythm. We concluded that physicians are still hesitant to use oral anticoagulants and antiplatelet agents for the prevention of strokes in their elderly patients with atrial fibrillation. These agents are used most frequently after an ischemic episode (transient ischemic attack or cerebrovascular accident) has occurred or in patients with mitral valve disease.

Topics: Administration, Oral; Aged; Aspirin; Atrial Fibrillation; Attitude of Health Personnel; Cerebrovascular Disorders; Dipyridamole; Drug Administration Schedule; Follow-Up Studies; Hemorrhage; Humans; Physicians; Platelet Aggregation Inhibitors; Surveys and Questionnaires; Warfarin

In order to determine optimum anticoagulation levels for the Medtronic Hall valve, the effect of low anticoagulation (mean International Normalized Ratio [INR] 2.5, 1979-1984) and moderate anticoagulation (mean INR 3.0, 1985-1989) was determined in 345 patients (183 low, 162 moderate) undergoing isolated mitral valve replacement (MVR) and 241 patients (91 low, 150 moderate) undergoing isolated aortic valve replacement (AVR). There were no cases of valve thrombosis. Embolic events and bleeding events were graded in severity and multiple decrement event-free survival calculated according to valve site and anticoagulation level: MVR low, MVR moderate, AVR low, and AVR moderate. In the MVR low group, 80% were free of all events and 93% free of serious events at 3 years compared with 89% and 98%, respectively, in the MVR moderate group. The AVR low group experienced a very small incidence of embolic events (one only) and no bleeding events. The AVR moderate group suffered more bleeding and more embolic events and at 3 years only 87% were event-free compared with 99% in the AVR low group. In both AVR groups, all embolic events were associated with one or more known stroke risk factors. Patients under 70, in sinus rhythm who were normotensive and were nonsmokers suffered no embolic events irrespective of their anticoagulation level. We conclude that the optimum INR for the average Medtronic Hall patient is 3.0 after MVR and 2.5 after AVR but some adjustments may be required in relation to stroke risk factor analysis.

Topics: Aortic Valve; Cerebrovascular Disorders; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Risk Factors; Thrombosis; Warfarin

Topics: Aged; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Middle Aged; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; 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

Topics: Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Humans; Warfarin

We studied platelet function in whole blood, a situation that better reflects the in vivo state, from 85 patients with acute ischemic stroke and from 19 healthy controls. Patients receiving no antithrombotic drugs demonstrated increased platelet dense body secretion without an associated increase in platelet aggregation, thus raising the possibility that dense body secretion may be of separate importance in cerebral infarction. Our results also suggest that dense body secretion may occur independently of aggregation. Heparin and heparin plus warfarin were ineffective in reducing the high level of dense body secretion seen in acute cerebral infarction, whereas treatment with aspirin plus dipyridamole inhibited both dense body secretion and platelet aggregation. It seems worthwhile to investigate the usefulness of antiplatelet drugs in the treatment of acute ischemic stroke wherein clinical outcome is correlated with the extent of suppression of platelet dense body secretion.

Topics: Acute Disease; Adult; Aspirin; Blood Platelets; Brain Ischemia; Cerebrovascular Disorders; Dipyridamole; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Platelet Function Tests; Warfarin

Topics: Aspirin; Cerebrovascular Disorders; Humans; Warfarin

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cerebrovascular Disorders; Female; Humans; Intracranial Embolism and Thrombosis; Recurrence; Tomography, X-Ray Computed; 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

Despite the widespread use of oral anticoagulants derived from 4-hydroxycoumarin, there have been only a small number of well-defined cases of hepatotoxicity. We report a well-defined case of cholestasis following exposure to warfarin sodium (Coumadin). Inadvertent rechallenge reproduced the syndrome. Cholestasis may occur in response to exposure to derivations of 4-hydroxycoumarin.

Topics: Aged; Cerebrovascular Disorders; Cholestasis; Humans; Male; Warfarin

Topics: Cerebrovascular Disorders; Drug Interactions; Female; Hemorrhage; Heparin; Humans; Infusions, Parenteral; Monitoring, Physiologic; Myocardial Infarction; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Surgical Procedures, Operative; Thromboembolism; Warfarin

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

The experience acquired in an anticoagulation clinic during 4 1/2 years is reviewed to demonstrate the effectiveness of such a clinic and to provide the practicing physician with guidelines for managing outpatient oral anticoagulation therapy. The experience is based on anticoagulant therapy in 141 patients during 1,264 patient-months. The patient population is characterized and aspects of management are explored, such as the incidence of major and minor complications (5% and 18% per treatment course, respectively), failure rate, and adequacy of therapy control. Guidelines concerning patient education, prothrombin time control, and other management suggestions are also given. This study, which compares favorably with others, is intended to aid the practicing physician and improve management of outpatient anticoagulation therapy.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Anticoagulants; Cerebrovascular Disorders; Female; Humans; Long-Term Care; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis; 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

"Purple toes" syndrome and a generalized skin eruption developed in a 73-year-old woman who was taking warfarin sodium (Coumadin) as well as antiarrhythmic agents after a stroke. Both the rash and the discoloration of her feet were apparently related to use of warfarin and gradually resolved after discontinuation of the drug.

Topics: Aged; Cerebrovascular Disorders; Female; Foot Dermatoses; Humans; Syndrome; Toes; 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

14 prospective, randomized trials dealing with non-operated patients were analyzed. In all of them the presence of deep vein thrombosis was measured by the radioactive iodine fibrinogen uptake test. Various prophylactic regimens were tested. 13 studies concern patients after myocardial infarction and one a cerebral hemorrhage patient. Only 2 trials confirm the value of oral couramin administration for the reduction of deep vein thrombosis after myocardial infarction. Two studies show that prophylactic anticoagulation with a full dose of heparin reduces the incidence of deep vein thrombosis after myocardial infarction. In 3 studies, again after myocardial infarction, a statistically significant reduction in the incidence of deep vein thrombosis is found when small doses of heparin are given. In 1 study investigating a few patients no effect could be shown. Low doses of heparin reduce the incidence of deep vein thrombosis after acute cerebral hemorrhage. Early mobilization has reduced the incidence of deep vein thrombosis in 21 patients after myocardial infarction, as compared to 8 patients treated with bed rest. Heavy smokers suffering myocardial infarction show a statistically significant lower incidence of deep vein thrombosis than non-smokers, as 3 papers confirm.

Topics: Cerebrovascular Disorders; Dose-Response Relationship, Drug; Early Ambulation; Heparin; Humans; Leg; Myocardial Infarction; Smoking; Thrombophlebitis; 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: Administration, Oral; Anticoagulants; Cerebrovascular Disorders; Drug Interactions; Hemorrhage; Humans; Postoperative Complications; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Warfarin

Topics: Aspirin; Brain; Cerebrovascular Disorders; Dipyridamole; Fibrinolytic Agents; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemia; Sulfinpyrazone; Warfarin

Four patients ages 20 to 38 years had repeated cerebrovascular occlusions. Three of the four patients had vascular headaches (classical migraine in two) for some years before their first occlusive event occurred. When first seen at the time of their major cerebrovascular occlusion, all had evidence of plasma hyper-coagulability, and two of the women were receiving birth control pills. Many months later, while off the "pill" and on warfarin sodium (Coumadin) therapy, two women and one man continued to have new cerebrovascular symptoms. For the first time, their platelet aggregability was tested to several biological substances known to come in contact with platelets in vivo. At this time, all four patients were found to have platelet hyperaggregability. The three symptomatic patients also had a shortened platelet survival time. Long-term management of these patients with chronic platelet aggregability and chronic plasma hyper-coagulability is described.

Topics: Adult; Aspirin; Blood Coagulation Tests; Blood Platelet Disorders; Cell Survival; Cerebrovascular Disorders; Contraceptives, Oral; Drug Therapy, Combination; Female; Humans; Male; Platelet Adhesiveness; Platelet Aggregation; Pregnancy; Pyridinolcarbamate; Recurrence; Sulfinpyrazone; 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: Abnormalities, Drug-Induced; Alcoholism; Cerebrovascular Disorders; Chondrodysplasia Punctata; Contraceptives, Oral; Diazepam; Female; Fetus; Furosemide; Humans; Hypertension; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Radiography; Rheumatic Heart Disease; Stress, Psychological; Warfarin

Topics: Aerospace Medicine; Cerebrovascular Disorders; Hematologic Diseases; Humans; Licensure; Pulmonary Embolism; Pulmonary Heart Disease; Thrombosis; Warfarin

Topics: Adult; Basilar Artery; Brain Stem; Cerebral Angiography; Cerebrovascular Disorders; Cervical Vertebrae; Chiropractic; Humans; Ischemic Attack, Transient; Male; Vertebral Artery; 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: Abdomen, Acute; Barium Sulfate; Blood Pressure; Blood Transfusion; Cerebrovascular Disorders; Duodenum; Female; Hematemesis; Hematuria; Hemoperitoneum; Humans; Intestinal Obstruction; Jejunum; Laparotomy; Male; Melena; Middle Aged; Myocardial Infarction; Prothrombin Time; Radiography; Vitamin K 1; Warfarin

Topics: Anticoagulants; Cerebral Angiography; Cerebrovascular Disorders; Heart Diseases; Hematoma; Hematuria; Hemorrhage; Humans; Pulmonary Embolism; Retroperitoneal Space; Toxicology; Warfarin

Topics: Arteriosclerosis; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Disease; Dicumarol; Diet; Diet Therapy; Family Practice; General Practice; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Myocardial Infarction; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Arrhythmias, Cardiac; Blood Cell Count; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Dicumarol; Heart Failure; Heparin; Humans; Hypertension; Kidney Diseases; Liver Diseases; Myocardial Infarction; Peptic Ulcer; Pulmonary Embolism; Shock; Thromboembolism; Thrombophlebitis; Thrombosis; Varicose Veins; Warfarin

Topics: Anticoagulants; Australia; Biomedical Research; Cerebrovascular Disorders; Drug Therapy; Nursing Homes; Phenindione; Toxicology; Warfarin

Topics: Acenocoumarol; Aged; Anticoagulants; Cerebrovascular Disorders; Coronary Disease; Dicumarol; Drug Therapy; Ethyl Biscoumacetate; Geriatrics; Humans; Incidence; Middle Aged; Mortality; Neoplasm Metastasis; Neoplasms; Pathology; Phenindione; Thromboembolism; Warfarin

Topics: Blood Coagulation Tests; Cerebrovascular Disorders; Coronary Disease; Crystallization; Dosage Forms; Drug Therapy; Toxicology; Vascular Diseases; Warfarin

Topics: Anticoagulants; Biomedical Research; Blood Coagulation Tests; Cerebrovascular Disorders; Coronary Disease; Drug Therapy; Factor VII; Hemorrhage; Humans; Phenindione; Prothrombin; Prothrombin Time; Rheumatic Heart Disease; Thromboembolism; Thrombophlebitis; Toxicology; Warfarin

Topics: Arteriosclerosis; Biomedical Research; Blood Chemical Analysis; Brain Diseases; Cerebrovascular Disorders; Coronary Disease; Enzyme Inhibitors; Fats; Hydrocortisone; Hypertension; Myocardial Infarction; Pharmacology; Physiology; Rabbits; Research; Thrombin; Warfarin