warfarin and Chronic-Disease

People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population.. To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm.. We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020. We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions.. Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month. We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party.. Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI).. We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect on all-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin may increase the risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxaban makes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR 0.67, 95% CI 0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR 1.65, 95% CI 1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence).. Based on the three RCTs, there is no evidence that oral anticoagulant therapy modifies mortality in people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events. There is no evidence of a difference in the effect of rivaroxaban on all-cause death compared to placebo. It probably reduces the risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.

Topics: Administration, Oral; Anticoagulants; Aspirin; Cardiomyopathy, Dilated; Chronic Disease; Heart Failure; Heart Rate; Hemorrhage; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thromboembolism; Warfarin

The decision to restart systemic anticoagulation after surgery requires a nuanced risk-benefit analysis. The potential for surgical site bleeding must be balanced against the risk of thromboembolic events. In the context of postoperative neurosurgical patients, the consequences of either hemorrhage or thromboembolism can be devastating. However, few studies to date have attempted to determine the optimal time to resume anticoagulation after craniotomy. As a result, the decision of when to restart anticoagulation remains largely subjective and highly variable between surgeons and institutions. In this study, we aim to develop an algorithm that incorporates existing metrics and expert opinion toward the goal of developing guidelines for restarting anticoagulation after elective craniotomy.

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Hemorrhage; Humans; Thromboembolism; Warfarin

Atrial fibrillation (AF) continues to impose a significant burden upon healthcare resources. A sustained increase in the ageing population and better survival from conditions such as ischaemic heart disease have ensured that both the incidence and prevalence of AF continue to increase significantly. AF can lead to complications such as embolism and heart failure and these acting in concert with its associated co-morbidities portend increased mortality risk. Whilst some studies suggest that the mortality risk from AF is due to the "bad company it keeps" i.e. the associated co-morbidities rather than AF itself; undoubtedly some of the mortality is also due to the side-effects of various therapeutic strategies (anti-arrhythmic drugs, bleeding side-effects due to anti-coagulants or invasive procedures). Despite several treatment advances including newer anti-arrhythmic drugs and developments in catheter ablation, anti-coagulation remains the only effective means to reduce the mortality due to AF. Warfarin has been used as the oral anticoagulant in the treatment of AF for many years but suffers from disadvantages such as unpredictable INR levels, bleeding risks and need for haematological monitoring. This has therefore spurred a renewed interest in research and clinical studies directed towards developing safer and more efficacious anti-coagulants. We shall review in this article the epidemiological features of AF-related mortality from several studies as well as the cardiovascular and non-cardiac mortality mechanisms. We shall also elucidate why a rhythm control strategy has appeared to be counter-productive and attempt to predict the likely future impact of novel anti-coagulants upon mortality reduction in AF.

Topics: Animals; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Chronic Disease; Humans; Warfarin

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and share a reciprocal relationship. The presence of AF increases the propensity to HF and can worsen its severity as well as escalating the risk of stroke. Despite the proven efficacy of vitamin K antagonists and warfarin for stroke prevention in AF, their use is beset by numerous problems. These include their slow onset and offset of action, unpredictability of response, the need for frequent coagulant monitoring and serious concerns around the increased risks of intracranial and major bleeding. Three recently approved novel anticoagulants (dabigatran, rivaroxaban and apixaban) are already challenging warfarin use in AF. They have a predictable therapeutic response and a wide therapeutic range and do not necessitate coagulation monitoring. In this article, the relationship between HF and AF and the mechanisms for their compounded stroke risk are reviewed. The evidence to support the use of these three NOACs amongst patients with AF and HF is further explored.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Chronic Disease; Dabigatran; Drug Monitoring; Heart Failure; Hemorrhage; Humans; Morpholines; Outcome Assessment, Health Care; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Warfarin

Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain patient groups, including patients with heart failure and atrial fibrillation, but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population.. To determine whether long-term oral anticoagulation reduces total deaths, cardiovascular deaths and major thromboembolic events in patients with heart failure.. We updated the searches in June 2030 in the electronic databases CENTRAL (Issue 6, 2013) in The Cochrane Library, MEDLINE (OVID, 1946 to June week 1 2013) and EMBASE (OVID, 1980 to 2013 week 23). Reference lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors were contacted to obtain further data. No language restrictions were applied.. Randomised controlled trials (RCTs) comparing oral anticoagulants with placebo in adults with heart failure, and with treatment duration at least one month. Non-randomised studies were also included for assessing side effects. Inclusion decisions were made in duplicate and any disagreement between review authors was resolved by discussion or a third party.. Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied by the 95% confidence intervals.. Two RCTs were identified. One compared warfarin, aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy. Three small prospective controlled studies of warfarin in heart failure were also identified, but they were over 50 years old with methods not considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there were no significant differences in the incidence of myocardial infarction, non-fatal stroke and death between patients taking oral anticoagulation and those taking placebo. Four retrospective non-randomised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results.. Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example those with atrial fibrillation), the available data does not support the routine use of anticoagulation in heart failure patients who remain in sinus rhythm.

Topics: Administration, Oral; Anticoagulants; Aspirin; Cardiomyopathy, Dilated; Chronic Disease; Heart Failure; Heart Rate; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Thromboembolism; Warfarin

Oral vitamin K antagonists are highly efficacious in the prevention and treatment of thromboembolic disease. Optimal use of these agents in clinical practice is challenged by their narrow therapeutic window. The proportion of time spent in the International Normalized Ratio (INR) range of 2.0-3.0 [time in the therapeutic range (TTR)] has been closely associated with adverse outcomes, i.e., stroke, hemorrhage, mortality. Although TTR is a validated marker, it has several limitations. TTR does not capture short-term risks associated with highly variable periods or periods characterized by extreme deviations in INR. Because TTR measurement is limited to consecutive periods of warfarin exposure, it does not inform the risks associated with gap periods of 56 days or greater as these time intervals are excluded from end-point rate calculations. Because individuals with gaps in monitoring represent a different patient population than those without gaps, e.g., less adherent, more acutely ill, more frequent transitions in health status, TTR analyses are likely most valid and informative for individuals with uninterrupted monitoring of the INR. Duration of warfarin therapy and patient-specific factors have also been shown to influence TTR. Younger age, female sex, lower income, black race, frequent hospitalizations, polypharmacy, active cancer, decompensated heart failure, substance abuse, psychiatric disorders, dementia, and chronic liver disease have all been associated with lower TTR. Targeted strategies to improve TTR are urgently needed.

Topics: Age Factors; Anticoagulants; Chronic Disease; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Liver Diseases; Male; Neoplasms; Sex Factors; Stroke; Substance-Related Disorders; Thromboembolism; Vitamin K; Warfarin

Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence rate. The highest incidence of recurrence is in the first 6 months. Active cancer significantly increases the hazard of early recurrence, and the proportions of time on standard heparin with an APTT ≥ 0.2 anti-X(a) U/mL, and on warfarin with an INR ≥ 2.0, significantly reduce the hazard. The acute treatment duration does not affect recurrence risk after treatment is stopped. Independent predictors of late recurrence include increasing patient age and body mass index, leg paresis, active cancer and other persistent VTE risk factors, idiopathic VTE, antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D-dimer. A recommendation for secondary prophylaxis should be individualized based on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding. The appropriateness of secondary prophylaxis should be continuously reevaluated, and the prophylaxis stopped if the benefit no longer exceeds the risk.

Topics: Age Factors; Anticoagulants; Antiphospholipid Syndrome; Body Mass Index; Chronic Disease; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Hyperhomocysteinemia; International Normalized Ratio; Neoplasms; Paresis; Protein C Deficiency; Protein S Deficiency; Recurrence; Risk Factors; Time Factors; Venous Thromboembolism; Warfarin

Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain groups, including patients with heart failure and atrial fibrillation, but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population.. To determine whether long-term oral anticoagulation reduces total deaths and/or major thromboembolic events in patients with heart failure.. We updated the searches in February 2010 on CENTRAL on The Cochrane Library (Issue 1, 2010), MEDLINE (2000 to February 2010) and EMBASE (1998 to February 2010). Reference lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors were contacted to obtain further data. No language restrictions were applied.. Randomised controlled trials (RCTs) comparing oral anticoagulants with placebo in adults with heart failure, and with treatment duration at least one month. Non-randomised studies were also included for assessing side-effects. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party.. Four review authors independently assessed trials for inclusion and assessed the risks and benefits from antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied with 95% confidence intervals.. Two RCTs were identified. One compared warfarin, aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy. Three small prospective controlled studies of warfarin in heart failure were also identified, but were over 50 years old with methods not considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there were no significant differences in the incidence of myocardial infarction, non-fatal stroke and death between patients taking oral anticoagulation and placebo. Four retrospective non-randomised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results.. Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example atrial fibrillation), the data available does not support its routine use in heart failure patients who remain in sinus rhythm. A large randomised trial of warfarin in heart failure patients in sinus rhythm is currently in progress and data from this trial will be a useful addition to this topic.

Topics: Administration, Oral; Anticoagulants; Aspirin; Chronic Disease; Heart Failure; Heart Rate; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Thromboembolism; Warfarin

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.

Topics: Administration, Oral; Aged; Anticoagulants; Cardiovascular Diseases; Chronic Disease; Female; Humans; Male; Middle Aged; Perioperative Care; Prognosis; Thromboembolism; Warfarin

The optimal antithrombotic strategy for patients with chronic oral anticoagulation undergoing coronary stenting is unknown. Our study conducted a meta-analysis of 9 previous trials comparing the safety and efficacy of triple antithrombotic regimen (including warfarin, aspirin and clopidogrel) to non-triple antithrombotic regimens in those patients.. Two investigators independently searched Pubmed, Ovid and Elsevier databases for all reported studies, and yielded 9 (of 242 potentially relevant) articles, published before July 2009, enrolling 5181 patients, follow-up period ranging from 1 month to 18 months. Two coauthors independently recorded the data regarding interventions and the occurrence of major bleeding, stroke, myocardial infarction and death.. Patients with triple antithrombotic regimen had significant reduction in ischemic stroke (odds ratio [OR] is 0.29, 95% confidence interval [CI] is from 0.15 to 0.58; and P=0.0004) as compared with dual antiplatelet therapy. While there was a two-fold increased risk of major bleeding associated with triple antithrombotic regime (OR 2.00, 95% CI 1.41 to 2.83; and P<0.0001). The overall incidence of death (OR 1.20, 95% CI 0.63 to 2.27, and P=0.56) and myocardial infarction (OR 0.84, 95% CI 0.57 to 1.23; and P=0.38) was comparable between the two regimens.. Our study confirmed the cardiovascular benefits of triple antithrombotic regimen by reducing ischemic stroke risk, but also demonstrated its increased risk of major bleeding. It poses imperative demands for future prospective randomized studies to define the optimal antithrombotic regimen in patients requiring chronic anticoagulation undergoing coronary stenting.

Topics: Administration, Oral; Anticoagulants; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Stents; Ticlopidine; Treatment Outcome; Warfarin

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

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

Warfarin is commonly used to prevent stroke in patients with atrial fibrillation; however, patients on haemodialysis may not derive the same benefit from warfarin as the general population. There are no randomized controlled studies in dialysis patients which demonstrate the efficacy of warfarin in preventing stroke. In fact, warfarin places the dialysis patient at increased risk for haemorrhagic stroke and possibly ischaemic stroke. Additionally, warfarin increases the risk of major bleeding and has been associated with vascular calcification. Routine use of warfarin in dialysis for stroke prevention should be discouraged, and therapy should only be reserved for dialysis patients at high risk for thrombo-embolic stroke and carefully monitored if implemented.

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Renal Dialysis; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Chronic Disease; Dabigatran; Humans; Pyrazoles; Pyridones; Recurrence; Risk Assessment; Venous Thromboembolism; Warfarin

Topics: Animals; Anticoagulants; Calcinosis; Chronic Disease; Humans; Renal Dialysis; Renal Insufficiency; Vascular Diseases; Vitamin K; Vitamin K Deficiency; Warfarin

This is a review of stroke mechanisms and management. The concept of stroke and transient ischemic attack and the recently proposed revision in definitions and controversies are discussed. We also discuss the use of antiplatelet and anticoagulant drugs for stroke due to carotid and cardiac disease.

Topics: Anticoagulants; Chronic Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Kidney Diseases; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Warfarin

Heart failure is commonly associated with vascular diseases and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. The incidence of thromboembolism in heart failure patients (which may include stroke, peripheral embolism, pulmonary embolism) seems to be around 2%, based on the data available from several small studies. However, the incidence of thromboembolism should greatly depend upon what is being looked at in each of these studies, as it will (generally) not be individually categorised. There is very little true epidemiological data to base this figure. The pathophysiology of heart failure is complex. There are many well- recognised factors, which are associated with thrombosis in heart failure patients, such as vascular abnormalities, increased coagulability and impaired blood flow. In the past 50 years, many studies have been performed to find out if oral anticoagulation is of benefit for the prevention of thromboembolism in patients with heart failure. Expert therapeutic guidelines in the Europe and North America agree that there is insufficient evidence to recommend that antithrombotic therapy should be given to patients with heart failure, unless they have atrial fibrillation or, perhaps, a previous thrombo-embolic episode. There is a lack of evidence for any antithrombotic agent that is effective in patients with heart failure; therefore, randomised clinical trials need to be designed to test the hypothesis that patients with chronic heart failure would have benefit from anticoagulant therapy. This review summarises the incidence, potential mechanism and therapeutic approaches for the management of thromboembolism in heart failure.

Topics: Anticoagulants; Chronic Disease; Heart Failure; Heparin; Humans; Molecular Weight; Survival Rate; Thromboembolism; Thrombosis; Warfarin

The chronic idiopathic urticaria treatment is a difficult and often frustrating problem for physicians. Due to the lack of definitive medical therapeutic programs to relieve the symptoms and prevent from their recurrence, several pharmacologic approaches to the management of chronic idiopathic urticaria are proposed. The chronic urticaria pharmacologic therapy is therefore fit to abrogate effects of histamine and other mediators on cutaneous vasculature and inflammatory cells that participate in the pathogenesis of the urticaria. The most common approach is to avoid all aggravating factors and to block histamine. The mainstay therapy is the H1 antihistamines. A significant number of patients may remain unresponsive even after an increase in the dose or a change in the type of H1 antihistaminic drug. In these cases, several therapies can be associated: combinations of H1 antihistamines, nonsedating one tablet (morning) and one sedating (evening), this approach is very usual but no study has confirmed it rational; addition an H2 antagonist to the previous treatment for some patients may improve control of their symptoms; alternatively, the tricyclic antidepressant, Doxepin is usually prescribed. The results of other drugs reported in the literature is unpredictable, to include them in a strategy therapy. The results with Badrenergic agents, nifedipine, ketotifen, leukotriene antagonists and tranexamic acid are variable and don't appear better than those with H1 antagonists. The efficiency of danazol has to be confirmed by other controlled studies. Warfarin, sulfasalazine and ultraviolet radiation have been used apparently successfully, but no controlled study has been published. Only when the above treatments have failed then immunosuppresive therapies, intravenous immunoglobulin and plasmapheresis can be proposed for chronic idiopathic urticaria.

Topics: Adrenergic beta-Agonists; Androgens; Anti-Allergic Agents; Antidepressive Agents, Tricyclic; Calcium Channel Blockers; Chronic Disease; Drug Resistance; Histamine H1 Antagonists; Histamine Release; Humans; Immunosuppressive Agents; Leukotriene Antagonists; Plasmapheresis; Ultraviolet Therapy; Urticaria; Warfarin

Topics: Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Echocardiography, Transesophageal; Embolism; Humans; Middle Aged; Practice Guidelines as Topic; 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

In the absence of randomized, controlled trials of low-dose amiodarone in atrial fibrillation or a randomized, controlled trial of ventricular rate control versus antifibrillatory therapy, a Markov decision analysis is useful in comparing different therapeutic strategies for atrial fibrillation. The decision analysis described compared warfarin, quinidine, and low-dose amiodarone in patients with asymptomatic or minimally symptomatic chronic, persistent atrial fibrillation. This model suggests that electrical cardioversion followed by low-dose amiodarone is a relatively safe, effective alternative to long-term warfarin therapy.

Topics: Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Decision Support Techniques; Electric Countershock; Humans; Markov Chains; Quinidine; Randomized Controlled Trials as Topic; Warfarin

To compare the relative risks and benefits of several clinical strategies for managing patients with chronic atrial fibrillation.. Five recent randomized controlled trials of warfarin in atrial fibrillation, 6 randomized controlled trials of quinidine, and 13 longitudinal studies of low-dose amiodarone were used. A MEDLINE search was also done (1966 to present).. A Markov decision analysis model was used to assess outcomes in large, hypothetical cohorts of patients with atrial fibrillation followed from 65 to 70 years of age within four clinical strategies: 1) no treatment; 2) warfarin; 3) electrical cardioversion followed by quinidine to maintain normal sinus rhythm; and 4) electrical cardioversion followed by low-dose amiodarone.. IN this hypothetical cohort, fewer patients had disabling events with amiodarone (1.4%) than with quinidine (1.8%), warfarin (2.6%), or no treatment (7.4%). Amiodarone appeared to be associated with the lowest 5-year mortality (13.6%) when compared with warfarin (14.4%), quinidine (15.2%), and no treatment (18.2%). In terms of quality-adjusted life-years, amiodarone had the highest expected value (4.75 years), followed by warfarin (4.72 years), quinidine (4.68 years), and no treatment (4.55 years). Amiodarone remained the preferred strategy using the most plausible scenarios of risks associated with atrial fibrillation. Choices among warfarin, quinidine, and no treatment depended on estimates of bleeding rates with warfarin, stroke rates after discontinuing warfarin, quinidine-related mortality, and the quality of life with warfarin.. Cardioversion followed by low-dose amiodarone to maintain normal sinus rhythm appears to be a relatively safe and effective treatment for patients with chronic atrial fibrillation.

Topics: Aged; Amiodarone; Atrial Fibrillation; Chronic Disease; Decision Support Techniques; Humans; Markov Chains; Quality of Life; Quinidine; Risk Factors; Warfarin

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Cerebral Infarction; Chronic Disease; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Humans; Middle Aged; 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

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery.. The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery.. There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups.. Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Topics: Anticoagulants; Chronic Disease; Endarterectomy; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

The objective of this study was to characterize the effects of risankizumab on the in vivo activity of cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in psoriasis patients using a cocktail approach.. Patients with moderate to severe chronic plaque psoriasis (n = 21) received single oral doses of sensitive probe substrates for CYP1A2 (caffeine 100 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), CYP2D6 (metoprolol 50 mg), and CYP3A (midazolam 2 mg) on day 1, followed by 12 weeks of subcutaneous risankizumab treatment of 150 mg once every 4 weeks from day 8 to day 92, and again the same cocktail of substrates on day 98. Serial blood samples were collected for determination of the CYP probe drugs and metabolites with and without risankizumab. Trough samples were collected for risankizumab.. The 90% confidence intervals (CIs) for the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC. Risankizumab did not affect the in vivo activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A enzymes in patients with moderate or severe plaque psoriasis and therefore has no potential for drug interactions through these enzymes.. ClinicalTrials.gov Identifier: NCT02772601.

Topics: Antibodies, Monoclonal; Area Under Curve; Caffeine; Chronic Disease; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Injections, Subcutaneous; Male; Midazolam; Omeprazole; Psoriasis; Severity of Illness Index; Substrate Specificity; Warfarin

Topics: Anticoagulants; Blood Loss, Surgical; Chronic Disease; Endoscopy; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Rhinitis; Sinusitis; Warfarin

The primary objective of this study was to evaluate the safety of early warfarin resumption following burr hole drainage for warfarin-associated subdural hemorrhage (SDH). This prospective, single-arm, single-center trial was conducted from February 2008 to April 2010. Inclusion criteria were premorbid warfarin therapy, subacute or chronic SDH requiring burr hole drainage, and an International Normalized Ratio (INR) of >1.5 at presentation. Three days after surgery, warfarin was re-administered to reach the target INR range of 1.7-2.5. Patients were followed by regular INR monitoring and serial brain CT scans, which were performed at 1 week, and at 1, 3, and 6 months after surgery. The primary outcome was recurrent SDH incidence. Twenty patients were enrolled and CT scans performed at 1 week revealed no new intracranial hemorrhage in any patient. Subsequent scans were performed at 1 month on 19 patients, and recurrent SDH was observed in three. However, this recurrence rate (15.8%; 95% CI 0,34) did not exceed that of ordinary SDHs, and all recurrent SDHs were successfully managed by repeated burr hole drainage. The other 16 patients completed their 6-month follow-ups uneventfully. SDH recurrence was found to be associated with older age (≥ 75 years), and a thicker SDH (≥ 25 mm), but not with post-operative anticoagulation status. None of the study subjects experienced a thromboembolic event during the study period. Restarting warfarin therapy does not need to be withheld for more than 3 days after burr hole drainage, particularly in patients with a high thromboembolic risk.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Decompression, Surgical; Drug Administration Schedule; Female; Hematoma, Subdural; Humans; Male; Middle Aged; Postoperative Hemorrhage; Prospective Studies; Suction; Time Factors; Trephining; Warfarin

In this study, our aim was to evaluate the effect of a higher dose of atorvastatin on the recurrence rate of atrial fibrillation (AF) after electrical cardioversion (EC) in addition to antiarrhythmic therapy.. 48 patients with persistent AF were included in this study. The patients were randomized to an atorvastatin 40-mg treatment group and a control group. Atorvastatin was started 3 weeks before EC and was continued for 2 months after EC. EC was performed using biphasic shocks after 3 weeks of treatment with the orally administered anticoagulant warfarin. Lipid and inflammatory parameters (high-sensitivity C-reactive protein, white blood cell count and fibrinogen level) were evaluated at the baseline and before EC. The endpoint of this study was electrocardiographically confirmed recurrence of AF of >10 min.. There were no significant differences in baseline characteristics and lipid and inflammatory marker levels between the treatment and control groups. Total cholesterol and low-density lipoprotein levels were significantly decreased in patients taking atorvastatin for 2 months compared with baseline values (174 ± 31 vs. 129 ± 25 mg/dl, p = 0.001, and 112 ± 23 vs. 62 ± 20 mg/dl, p = 0.001, respectively), while no significant change occurred in control patients (168 ± 26 vs. 182 ± 29 mg/dl, p = 0.07, and 99 ± 18 vs. 108 ± 26 mg/dl, p = 0.1, respectively). At the end of the 2-month follow-up period, 9 patients (20.5%) experienced AF recurrence, and there was no significant difference in AF recurrence rate between the treatment and control groups (26 vs. 13%; p = 0.2).. Atorvastatin therapy prior to EC does not prevent the recurrence of arrhythmia in patients with persistent AF who are receiving antiarrhythmic therapy.

Topics: Analysis of Variance; Anti-Arrhythmia Agents; Anticholesteremic Agents; Anticoagulants; Atorvastatin; Atrial Fibrillation; C-Reactive Protein; Chronic Disease; Electric Countershock; Female; Fibrinogen; Health Status Indicators; Heptanoic Acids; Humans; Leukocyte Count; Male; Middle Aged; Pyrroles; Secondary Prevention; Time Factors; Warfarin

The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown.. Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%).. Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively).. Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Coagulation; Canada; Chi-Square Distribution; Chronic Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.. This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women >/=18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Chronic Disease; Clopidogrel; Death; Double-Blind Method; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Stroke; Stroke Volume; Ticlopidine; Warfarin

Previous reparative valvular surgical options directed at reconstructing damaged common femoral vein (CFV) valves associated with pathological chronic venous insufficiency (CVI) have not succeeded in reliably managing CVI. In consequence, venous valvuloplasty is rare and most patients are managed conservatively. As a result, monocusp surgery was identified as an optional surgical solution for this large underserved patient group.. Ulcer patients appear at wound clinics and often experience disappointing results. Monocusp valves were constructed utilizing viable vein wall in 14 operations on 11 patients. These patients were observed for four years to see if such an autogenous vein wall valve might control aggressive symptomatic CVI when faced with unusable valves.. Long-term follow-up showed that the monocusp valves remained competent at four years. Symptomatic failures have not appeared at this time. Pain, swelling, ulcers and leg congestion were reliably reversed. VEnous INsufficiency Epidemiologic and Economic Study (VEINES) classification (see Abenhaim L, Krux X, VIENES Study collaborators. Angiology 1997;48:59 and Kurz X, Kahn SR, Abenhaim L, et al. Int Angiol 1999;18:83-102) improved over four years from 2.7 +/- 0.9 to 0 (P < 0.001); CEAP classifications (see Kistner RL, Eklof B, Masuda EM. Mayo Clin Proc 1996;71:338-45) improved from grade 4-6 to 0-1 (CEAP is not generally a postoperative grading system, but it can be used to develop some form of qualitative analyses as to intervention effectiveness, i.e. what existed preoperatively no longer exists postoperatively. Its postsurgery use is limited by (C5) classification - history of ulcer, which by definition cannot go below that with a history of ulcer even if the ulcer has been cured). Mean venous reflux scores decreased from 3.8 +/- 0.4 to 0.3 +/- 0.5 (P < 0.001).. Monocusp implantation reliably resolved patient symptoms when unusable CFV valves were encountered. Postoperative CFV reflux is usually undetectable. The monocusp valve exhibits minimal thrombogenicity related to its viability with attendant antithrombotic hormone production capacity and has markedly improved the patient's quality of life. Full thickness monocusp surgery could become widespread with the difficult dysplastic/aplastic CVI patient subset because of its simplicity, repeatability, durability, low complication rate, effectiveness, persistent availability and viability providing nitric oxide synthase and thymomodulin hormone production capacity. The full thickness of vein wall has distinct advantages over other partial thickness valve creation methods because of its long-term vitality. Postoperative coumadin is recommended for six months to minimize risks of deep vein thrombosis and/or pulmonary embolism.

Topics: Anticoagulants; Chronic Disease; Feasibility Studies; Femoral Vein; Humans; Pulmonary Embolism; Quality of Life; Severity of Illness Index; Surgical Flaps; Suture Techniques; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Surgical Procedures; Venous Insufficiency; Venous Thrombosis; Warfarin

To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group.. 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat.. Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively).. During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bradycardia; Cardiac Pacing, Artificial; Chronic Disease; Confidence Intervals; Female; Humans; Incidence; Male; Middle Aged; Regression Analysis; Risk Factors; Sick Sinus Syndrome; Syndrome; Tachycardia, Supraventricular; Telemetry; Thromboembolism; Warfarin

This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin.. Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. METHODS; We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. RESULTS; Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p < 0.001), enhanced plasma levels of soluble P-selectin (p < 0.001) and had no significant effect on platelet aggregation. Aspirin-clopidogrel combination therapy made no difference to the plasma markers of thrombogenesis or platelet activation (all p = NS), but the platelet aggregation responses to adenosine diphosphate (p < 0.001) and epinephrine (p = 0.02) were decreased.. Aspirin-clopidogrel combination therapy failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Clopidogrel; Cross-Sectional Studies; Drug Therapy, Combination; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; P-Selectin; Peptide Fragments; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Prothrombin; Ticlopidine; Treatment Outcome; Warfarin

Tissue factor (TF; an initiator of coagulation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis) are involved in the hypercoagulable state associated with malignancy. We investigated their roles in chronic atrial fibrillation (AF), a condition also associated with increased risk of stroke and thromboembolism, as well as a prothrombotic or hypercoagulable state.. We studied 25 patients with AF (20 men; mean+/-SD age, 62+/-13 years) who were compared with 2 control groups in sinus rhythm: 30 healthy control subjects (17 men; mean age, 60+/-9 years) and 35 patient control subjects with coronary artery disease (CAD; 27 men; mean age, 60+/-12 years). Plasma levels of TF, VEGF, and the VEGF receptor sFlt-1 were measured by enzyme-linked immunosorbent assay.. VEGF, sFlt-1, and TF were significantly different between the 3 groups, with abnormal levels in AF and CAD patients compared with control subjects (P<0.001, P=0.022, and P=0.008, respectively). Among the AF patients, TF levels were significantly correlated with VEGF (Spearman's r=0.65, P<0.001) and sFlt (r=0.54, P=0.006) levels. Only TF and VEGF levels were significantly correlated in CAD patients (r=0.39, P=0.02). There were no significant correlations among the healthy control subjects.. Patients with chronic AF have high TF levels, in keeping with the prothrombotic state associated with this arrhythmia. The relationships between TF and VEGF and its receptor sFlt-1 in AF suggest a possible role for VEGF in the hypercoagulable state found in AF, as seen in malignancy and atherosclerosis.

Topics: Anticoagulants; Atrial Fibrillation; Blood Pressure; Case-Control Studies; Chronic Disease; Coronary Artery Disease; Cross-Sectional Studies; Demography; Endothelial Growth Factors; Female; Humans; Lymphokines; Male; Middle Aged; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Thrombophilia; Thromboplastin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Warfarin

The increased risk of stroke and thromboembolism in atrial fibrillation (AF) may be related to a prothrombotic or hypercoagulable state, with abnormalities of hemostasis and platelet activation. To investigate the role of platelets in AF and the influence of antithrombotic therapy, we developed and then applied a new assay to detect the absolute amount of P-selectin per platelet (pP-selectin) based on cell lysis. Thus, pP-selectin in AF patients was compared with that of healthy controls and also with plasma soluble P-selectin (sP-selectin) and beta-thromboglobulin as established indices of platelet activation. METHODSMDSAH: We studied 122 patients (mean [SD] age, 71 [9] years; 65 men) with chronic AF of >6 weeks' duration: 34 were not on antithrombotic therapy, 30 were taking aspirin (75 to 300 mg/d), and 58 were fully anticoagulated with warfarin. pP-selectin was compared with sP-selectin and plasma beta-thromboglobulin levels (enzyme-linked immunosorbent assay). Results were compared with those of 23 healthy controls (mean [SD] age, 74 [9] years; 7 men) in sinus rhythm.. pP-selectin was significantly lower in AF patients on no antithrombotic therapy (P=0.03) than in healthy controls, but sP-selectin and beta-thromboglobulin levels were not significantly different and did not differ in patients taking aspirin or warfarin. However, pP-selectin was lower in patients with AF on aspirin than in those on warfarin (P<0.05). pP-selectin/sP-selectin correlated significantly in healthy controls (r=0.47, P=0.03) but inversely (r=-0.43, P=0.03) in AF patients on no antithrombotic therapy.. Lower levels of pP-selectin may represent a depletion of pP-selectin after platelet activation in AF. Aspirin further decreases pP-selectin levels compared with warfarin. On the basis of the principle of platelet lysis, we demonstrate that it is possible to determine the amount of P-selectin per platelet, which may be regulated in the megakaryocyte through a cyclooxygenase-dependent pathway.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; beta-Thromboglobulin; Blood Platelets; Cell Count; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Octoxynol; P-Selectin; Predictive Value of Tests; Reference Values; Warfarin

Recent clinical trials have established that adjusted-dose warfarin (international normalized ratio [INR] 2.0 to 3.0) is highly effective in the reduction of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). We hypothesized that the introduction of fixed low-dose warfarin alone or in combination with aspirin (300 mg) could normalize hemostatic markers, namely plasma fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor-1 (PAI-1, an index of fibrinolysis), fibrinogen, and von Willebrand factor (vWf, an index of endothelial dysfunction), in a manner comparable to adjusted-dose warfarin (target INR 2.0 to 3.0). METJODS: Sixty-one patients with AF (44 men, mean+/-SD age 64+/-19 years) who were not receiving any antithrombotic therapy were prospectively randomized into 1 of 3 treatment groups: warfarin (2 mg) (n=23; group 1), combination 1 mg warfarin plus 300 mg aspirin (n=21; group 2) or combination 2 mg warfarin plus 300 mg aspirin (n=17; group 3). Subjects from all 3 AF groups were matched for sex, age, and blood pressure. Blood samples were taken for sequential measurements for changes in plasma fibrin D-dimer, PAI-1, fibrinogen, and vWf before and at 2 and 8 weeks after randomization (phase 1). All patients were subsequently offered adjusted-dose warfarin therapy (phase 2), and an additional blood sample was taken 6 weeks later.. When pretreatment results were compared with those from 60 age- and sex-matched healthy control subjects in sinus rhythm, there were significant elevations in levels of fibrinogen (P=0.025), vWf (P<0.0001), and fibrin D-dimer (P<0.0001) in patients with AF compared with control subjects. There were no significant changes in the levels of various indices measured after 2 and 8 weeks of therapy in all 3 groups, except for an increase in PAI-1 level (P=0.024) in group 3. After 6 weeks of therapy with dose-adjusted warfarin (INR 2.0 to 3.0), there was a significant decrease in plasma fibrinogen (P=0.023) and fibrin D-dimer (P=0.0067) levels. There were no significant changes in the levels of PAI-1 (P=0.198) or vWf (P=0.33).. The present results confirmed that high levels of vWf, fibrinogen, and fibrin D-dimer levels were present in patients with AF compared with control subjects. Moreover, the introduction of 300 mg aspirin plus low-dose warfarin (1 mg/d), low-dose warfarin alone (2 mg/d), or 300 mg aspirin plus low-dose warfarin (2 mg/d) did not significantly reduce any of the hemostatic markers studied (except PAI-1 levels), whereas conventional full-dose warfarin (INR 2.0 to 3.0) significantly reduced levels of fibrin D-dimer and fibrinogen. These results are in keeping with the disappointing ineffectiveness of low-intensity warfarin therapy, aspirin-warfarin combination, and ultralow-dose warfarin therapy in the recent prematurely terminated clinical trials and the established benefits of conventional adjusted-dose anticoagulation therapy.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Dose-Response Relationship, Drug; Drug Combinations; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Platelet Aggregation Inhibitors; Prospective Studies; Reference Values; Thrombosis; von Willebrand Factor; Warfarin

Chronic idiopathic urticaria is a disabling condition that does not always respond to antihistamine drugs and other agents are sometimes needed to control disease activity. Warfarin has demonstrated efficacy in single unblinded case studies [1] but has been dismissed by others [2].. We investigated the effect of warfarin treatment in eight patients with chronic idiopathic urticaria unresponsive to antihistamines in an open study. Six of the eight patients responded to treatment and three had a dramatic response. These three were included in a double-blind placebo-controlled trial of warfarin therapy to confirm significant benefit from treatment.. The three warfarin responders had their stable warfarin dose encapsulated and placebo capsules were provided. A double-blind placebo-controlled crossover trial was performed on each patient. Visual analogue scores recorded disease activity.. Comparison of visual analogue scores showed a significant benefit while on warfarin with a reduction in pruritus and angio-oedema.. This is the first double-blind placebo-controlled study to show a response of chronic idiopathic urticaria to warfarin. The mechanisms of action are unclear and require further study.

Topics: Adult; Angioedema; Anticoagulants; Chronic Disease; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Histamine; Humans; Intradermal Tests; Male; Middle Aged; p-Methoxy-N-methylphenethylamine; Pain Measurement; Placebos; Urticaria; Warfarin

To compare the dosing requirements and international normalized ratios (INRs) associated with two bioequivalent crystalline warfarin sodium products in patients with chronic atrial fibrillation.. A multicenter, single-blind (prescriber), randomized, crossover evaluation of Apothecon warfarin and DuPont warfarin (Coumadin) was conducted in consenting adults with chronic or paroxysmal atrial fibrillation who had been receiving DuPont warfarin chronically for the prevention of thromboembolism. Patients were randomly assigned to initially either continue DuPont warfarin or receive Apothecon warfarin for four weeks, with weekly evaluation of dosage and INR changes, safety, and efficacy. Subsequently, patients crossed over and received the other product for four weeks.. There were 113 patients randomized to receive study treatment. Neither the propensity for a dosage change or an INR change nor the magnitude of a dosage change or INR change appeared related to a particular warfarin product (NS for each variable after each study period). After four weeks of treatment, the same number of patients (n = 7) experienced a > or = 20% change in warfarin dosage from the respective baseline with each product. The number of patients with INRs outside the desired protocol range after four weeks of treatment was similar for both groups (< 1.8, n = 9 for both products, or > 3.2, n = 9 for DuPont, n = 10 for Apothecon). No major hemorrhagic or thromboemoblic events occurred.. The results of this study show that Apothecon warfarin and DuPont warfarin provide equivalent anticoagulation in patients with chronic or paroxysmal atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Chronic Disease; Cross-Over Studies; Female; Humans; Male; Prospective Studies; 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

Percutaneous transluminal coronary angioplasty (PTCA) of chronic total coronary artery occlusions is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for chronic coronary occlusion has never been tested in a large patient sample. This study reports the first multicenter experience with the Wiktor stent for treatment of chronic occlusions.. From January 1993 to December 1996, 89 consecutive patients with 91 chronic occlusions underwent Wiktor stent implantation after successful PTCA. Post-stenting regimen consisted of coumadin plus aspirin in the first 49 (55%) patients and aspirin plus ticlopidine in the following 40 (45%).. Stenting was successful in 87 (98%) patients. At 1 month, 6% of patients had subacute stent thrombosis, 1% access-site complications and 3% major bleeding events. Stent thrombosis showed a univariate association with coumadin therapy (p = 0.009). Angiographic follow-up was obtained in 93% of 82 eligible patients. Restenosis rate was 32%, including 4% reocclusions. Through multiple logistic regression analysis, restenosis was independently associated with multiple stents (odds ratio-OR = 27.67, 95% confidence interval-CI = 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (OR = 1.23, 95% CI = 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87 and 72% at one and three years, respectively.. Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation for chronic coronary occlusion. Further technical refinements are needed to reduce restenosis rate in patients with long lesions and multiple stents.

Topics: Analysis of Variance; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Chronic Disease; Coronary Angiography; Coronary Disease; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Stents; Ticlopidine; Time Factors; Warfarin

A prospective study was designed to investigate potential changes of left atrial (LA) spontaneous echo contrast with time and the effects of antithrombotic therapy on its presence in 77 patients with chronic nonrheumatic atrial fibrillation (AF), using serial transesophageal echocardiography (TEE). During a mean follow-up period of 20 +/- 15 months (range 6 to 77), a total of 197 TEE studies were performed in these patients. Baseline TEE revealed that LA spontaneous echo contrast was absent in 43 patients (group 1) and present in 34 (group 2). LA thrombus was found in 8 of group 2 but in none of the group 1 patients. During the follow-up period, only 2 of the group 1 patients were receiving antithrombotic agents; the patients in group 2 without LA thrombus were treated with either warfarin or aspirin, whereas those with LA thrombus were treated with warfarin. On the latest TEE study, LA spontaneous echo contrast was observed in 19 of the group 1 patients (44%) and was persistently found in all of the group 2 patients. During the study period, no patient was found to develop new LA thrombus formation and only 4 episodes of transient ischemic attack were recorded in 4 patients (embolic event rate = 3.1% per year). Of these, 2 were observed in group 1 and the remaining 2 were from group 2 and under aspirin therapy (event rate = 2.2% and 4.7% per year, respectively). In the subgroup of patients with LA thrombus receiving warfarin therapy, follow-up TEE revealed complete resolution of the thrombi in 6 and partial resolution in the remaining 2 in spite of the persistence of LA spontaneous echo contrast; none of these patients developed clinical thromboembolic events during the study period. Thus, future occurrence of LA spontaneous echo contrast could be observed by serial TEE at a substantial rate in patients with nonrheumatic AF who have no LA spontaneous echo contrast; follow-up TEE should be recommended for these patients to detect early the potential occurrence of LA spontaneous echo contrast if preventive antithrombotic therapy is not considered. Although warfarin therapy is associated with resolution of LA thrombus, neither warfarin nor aspirin is effective for suppressing the presence of LA spontaneous echo contrast in nonrheumatic AF.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Disease Progression; Echocardiography, Transesophageal; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Prospective Studies; Thrombosis; Warfarin

To determine whether chronic atrial fibrillation is associated with abnormalities in plasma fibrinogen, von Willebrand factor (vWF) (a marker of endothelial disturbance), or fibrin D- dimer (a measure of fibrin turnover); and if so, whether such levels are related to haemodynamic disturbance (enlarged left atrium, poor left ventricular function) or existing treatment with warfarin or aspirin. To investigate the effects of introducing warfarin in patients with atrial fibrillation on fibrinogen and D- dimer levels.. Cross sectional population sample controlled study and longitudinal study of patients undergoing anticoagulation.. District general hospital.. 87 patients (44 men and 43 women of mean (SEM) age 63.0 (1.0)) with chronic atrial fibrillation. At the time of the study, 37 were taking no antithrombotic medication (group 1), 31 were taking warfarin (including two on warfarin and aspirin) (group 2) and 19 were taking aspirin alone (group 3). They were compared with 158 population controls from a random population sample (the second Glasgow monitoring trends and determinants in cardiovascular disease study). As part of clinical treatment warfarin was introduced in 20 patients with chronic atrial fibrillation (14 men and six women of mean (SEM) (range) age 63.9 (2.35 (32-74) years).. Plasma fibrinogen remained significantly increased in patients of group 1 (no antithrombotic medication) compared with that of the population controls (median difference 1.23 g/l; 95% confidence interval (CI) 0.88 to 1.62, P < 0.0001). There was also a significant increase in plasma D-dimer levels (median difference 77 ng/ml; 95% CI 38 to 122, P < 0.01) and vWF (median difference 63 IU/dl; 95% CI 38 to 89, P < 0.0001). There was no significant difference in plasma fibrinogen (median difference 0.14 g/l; 95% CI -0.44 to 0.77, P = 0.65) or vWF (median difference 3.5 IU/dl; 95% CI - 41 to 41, P = not significant in patients of group 2 (warfarin treatment) compared with that of patients in group 1. Levels of D-dimer were significantly lower in group 2 (median difference 90 ng/ml, 95% CI 39 to 150, P < 0.0001) than in group 1. There were no significant differences in plasma fibrinogen (median difference 0.08 g/l; 95% CI - 0.52 to 0.77, P = 0.73), D-dimer (median difference - 34 ng/ml; 95% CI - 114 to 21.0, P = 0.25), or vWF (median difference 2%; 95% CI - 35 to 41, P = not significant) levels between patients of groups 1 and 3. There were no significant correlations between the coagulation indices and left atrial volume or ventricular function. There was a significant positive correlation between plasma fibrin D-dimer and vWF levels in patients of groups 1 and 3 (r = 0.52, P < 0.001). There was a significant reduction in median plasma fibrin D-dimer levels at 2 months after the introduction of warfarin (181 ng/ml v 80 ng/ml, P < 0.001), but no effect on plasma fibrinogen.. Increased median plasma fibrinogen and vWF levels were found in patients with chronic atrial fibrillation. Plasma D-dimer levels were also increased in patients with chronic atrial fibrillation not receiving warfarin, suggesting increased intravascular thrombogenesis in such patients. Introduction of warfarin normalised circulating fibrin D- dimer levels, suggesting that warfarin treatment was effective in preventing excessive fibrin turnover, consistent with the antithrombotic effects of warfarin. These results suggest three possible thrombotic markers to assess patients with atrial fibrillation who are at high risk of thrombogenesis; D-dimer also merits assessment as a measure of reduction in thrombotic risk in patients receiving warfarin.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Longitudinal Studies; Male; Middle Aged; Thrombosis; von Willebrand Factor; Warfarin

Transesophageal echocardiography was used to assess cardiac abnormalities associated with embolization in patients who had completed the Department of Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs Medical Centers without an embolic event. Patients were men, 71 +/- 7 years old, with atrial fibrillation of 6.2 +/- 4.3 years' duration who had received warfarin (n = 32) or placebo (n = 23) for 2 years. Thrombi were found in 5 of 55 patients (warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of 5 patients. Other abnormalities identified included spontaneous echo contrast (47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5 patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not predict subsequent outcome. Thus warfarin therapy did not preclude the presence of thrombi. Stroke reduction likely involves the prevention of emboli from sources in addition to the atrial appendage.

Topics: Aged; Atrial Fibrillation; Blood Flow Velocity; Chi-Square Distribution; Chronic Disease; Echocardiography, Transesophageal; Follow-Up Studies; Heart Aneurysm; Heart Atria; Heart Diseases; Heart Septal Defects, Atrial; Heart Septum; Heart Ventricles; Humans; Male; Middle Aged; Prevalence; Rheumatic Heart Disease; Thrombosis; 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

From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Denmark; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Random Allocation; Thromboembolism; Warfarin

Topics: Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Humans; Thromboembolism; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear.. The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH.. Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding.. Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032).. This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Chronic Disease; Cohort Studies; East Asian People; Hemorrhage; Humans; Hypertension, Pulmonary; Prospective Studies; Retrospective Studies; Thromboembolism; Warfarin

Endovenous revascularization is the standard in the management of acute thrombotic, chronic post-thrombotic iliocaval or iliofemoral obstruction, and nonthrombotic iliac vein lesions. The purpose of this study is to describe our single-center experience of postprocedure anticoagulation and antiplatelet regimens used after endovenous revascularization for a variety of venous occlusive conditions.. We conducted a retrospective analysis of 100 consecutive patients who underwent endovenous stenting for iliocaval or iliofemoral obstruction from January 1, 2014, to April 30, 2018. Patients treated with direct oral anticoagulants, warfarin, or low-molecular-weight heparin (LMWH) with or without antiplatelet therapy were identified. Demographic, procedural, patency, and follow-up data were collected. Stent patency was evaluated using duplex Doppler ultrasound examination or contrast venography.. Seventy-one of 100 patients were treated with direct oral anticoagulant therapy (DOAC). Sixteen (23%) were lost to follow-up, leaving 55 (77%) available for analysis. The mean follow-up was 14 months (range, 1-43 months) with 32 patients (58%) followed for 12 months or longer. Primary, primary-assisted, and secondary-assisted patency rates were 87%, 97%, and 98%, respectively, at 12 months. In the non-DOAC group (patients treated with warfarin or LMWH), these rates were 87%, 93%, and 95%, respectively, at 12 months. Antiplatelet therapy, including clopidogrel, aspirin, or both, was used in 53 of 55 patients in the DOAC cohort and 18 of 19 patients in the non-DOAC group.. Our-single center retrospective analysis demonstrates acceptable primary patency rates when using DOAC therapy compared with those treated with warfarin or LMWH.

Topics: Administration, Oral; Anticoagulants; Chronic Disease; Endovascular Procedures; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postthrombotic Syndrome; Retrospective Studies; Stents; Tertiary Care Centers; Time Factors; Treatment Outcome; Vascular Patency; Venous Thrombosis; Warfarin

The aim was to compare the safety and effectiveness of rivaroxaban and warfarin as anticoagulants for treating patients with post-thrombotic syndrome (PTS) with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting.. This single institution retrospective study analysed patients with PTS with chronic iliofemoral venous occlusion who were prescribed rivaroxaban or warfarin for one year after successfully undergoing iliofemoral venous stenting. The primary safety and efficacy endpoints were bleeding complication rate and primary patency rate at one year. Secondary outcomes included Villalta score, symptom recurrence rate, ulcer healing rate, and clinically driven target lesion revascularisation (CD-TLR) rate during follow up.. From January 2016 to December 2017, 154 legs from 154 patients were included in this study (69 in rivaroxaban group and 85 in warfarin group). The groups were well matched for patient demographics, clinical characteristics, and procedural details. There was no significant difference between the rivaroxaban group and warfarin group in bleeding complication rate (10% vs. 16%, p = .23, hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.25 - 1.37) at one year, as well as major bleeding complication rate (0% vs. 2%, p = .20, HR 0.16, 95% CI 0.01 - 2.61) and minor bleeding complication rate (10% vs. 14%, p = .40, HR 0.67, 95% CI 0.27 - 1.66). The primary patency rate was higher in the rivaroxaban group at one year (84% vs. 71%, p = .049, HR 0.50, 95% CI 0.26 - 0.96) and at two years (79% vs. 63%, p = .037, HR 0.52, 95% CI 0.29 - 0.93). At a mean follow up of 24 months (range 1 - 42 months), the rivaroxaban group had a significantly lower post-operative Villalta score (4.87 ± 3.51 vs. 6.88 ± 5.85, p = .010, t = 2.64, 95% CI 0.50 - 3.52), lower rate of symptom recurrence (4% vs. 32%, p < .001), lower CD-TLR rates (3% vs. 13%, p = .039), and higher ulcer healing rate (90% vs. 59%, p = .004) than the warfarin group.. For PTS patients with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting, rivaroxaban probably exhibited similar safety but superior efficacy to warfarin. However, further prospective control studies with large sample size are necessary to confirm the results.

Topics: Aged; Anticoagulants; Chronic Disease; Databases, Factual; Endovascular Procedures; Factor Xa Inhibitors; Female; Femoral Vein; Hemorrhage; Humans; Iliac Vein; Male; Middle Aged; Postthrombotic Syndrome; Registries; Retrospective Studies; Rivaroxaban; Stents; Time Factors; Treatment Outcome; Vascular Patency; Warfarin

We present a case of a 38-year-old man with a history of chronic thromboembolic pulmonary hypertension on therapeutic anticoagulation and recent hospitalisation for COVID-19 disease who was hospitalised for recurrent acute pulmonary embolism despite therapeutic anticoagulation with warfarin (International Normalized Ratio (INR) of 3.0). Our case highlights the hypercoagulable state associated with COVID-19 disease and the absence of standardised approaches to anticoagulation treatment for this population.

Topics: Adult; Anticoagulants; Chronic Disease; COVID-19; Diagnosis, Differential; Humans; Male; Pulmonary Artery; Pulmonary Embolism; SARS-CoV-2; Tomography, X-Ray Computed; Warfarin

Dabigatran is an orally active direct thrombin inhibitor, initially approved by FDA for the prophylaxis of stroke and systemic embolism in the setting of non-valvular atrial fibrillation (NVAF). Major bleeding is its most common adverse event which is of great concern. However, other types of adverse events such as esophagitis, esophageal ulcer, exanthem and pustular eruptions were reported increasingly in recent years. We present a case of immune hemolytic anemia (IHA) due to dabigatran use in a 72-year-old male with NVAF. This new and rare reported type of adverse event associated with dabigatran suggests that dabigatran may be a new cause of drug-induced immune hemolytic anemia (DIIHI).

Topics: Aged; Anemia, Hemolytic, Autoimmune; Antithrombins; Chronic Disease; Dabigatran; Disease Progression; Drug Substitution; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Male; Treatment Outcome; Warfarin

Little is known about how warfarin is prescribed for stroke prevention in maintenance dialysis patients with chronic atrial fibrillation (AF). We examined patterns of warfarin use, and associated factors, after AF diagnosis. This retrospective cohort analysis studied US Medicare patients receiving maintenance dialysis January 1, 2008, to June 30, 2010. Demographics, co-morbidity, and a durable medical equipment claims-based disability proxy score predicted warfarin prescription after AF diagnosis. The analysis included 8,964 patients with nonvalvular AF. Compared with nonusers, warfarin users were younger (age 65.4 ± 12.1 vs 67.0 ± 12.9 years) and more likely to be men (54.3% vs 52.8%) and of white race (64.0% vs 59.6%). After adjustment for other factors, nonwhite, versus white, race was associated with significantly less warfarin use within 30 days: odds ratios (ORs), 95% confidence intervals (CIs), were 0.80, 0.71 to 91, for black patients; 0.57, 0.43 to 0.76, for Asians; and 0.74, 0.49 to 1.12, for members of other races. Percentages of patients receiving warfarin decreased as Hypertension Abnormal renal and liver function Stroke-Bleeding Labile INR Elderly Drugs or alcohol (HAS-BLED) bleeding risk score increased (OR 0.82, 95% CI 0.73 to 0.92, HAS-BLED score 3 to 4 versus 2; 0.38, 0.26 to 0.57, score ≥ 5 vs 2). However, as CHA

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Ethnicity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Practice Patterns, Physicians'; Renal Dialysis; Retrospective Studies; Stroke; United States; Warfarin; White People; Young Adult

Topics: Administration, Oral; Anticoagulants; Chronic Disease; Female; Hemorrhage; Humans; Liver Diseases; Male; Middle Aged; Retrospective Studies; Venous Thromboembolism; Warfarin

To assess the quality of real-life warfarin anticoagulation in patients requiring chronic thromboprophylaxis in a southern Croatian county.. We retrospectively analyzed international normalized ratio (INR) values determined over one year (2016-2017) at the Zadar County General Hospital in warfarin-treated patients requiring chronic thromboprophylaxis. The values represent 83.0% of all INRs and were determined in 84.0% of all warfarin-treated patients in the county during the observed period.. Overall 31162 INRs were taken from 3697 patients, 2240 of whom (20 851 INRs, 3-56 per patient, median 9) were referred with diagnoses requiring chronic thromboprophylaxis: mainly atrial fibrillation/flutter (n=1508, 14902 INRs) but also cardiac implants, valvular disease, severe heart failure, and cerebrovascular disease ("other", n=732, 5949 INRs). Only 50.1% of all INRs were within the target range, 2.0-3.5, while 43.6% were <2.0, and 6.3% were >3.5. Median crude individual proportion of INRs within the range was 50.0%, while it was 42.0% for INRs <2.0. Only 23.0% of the patients had ≥70% of the INRs within the target range (adequately anticoagulated), while 35.5% had ≤33.3% of the INRs within the range. Conversely, 66.5% of the patients had ≥33.3% INRs <2.0. Adjusted probability of adequate anticoagulation in atrial fibrillation/flutter patients was consistently 25.5% to 27.7%, regardless of the number of determined INRs, while in patients with other conditions it increased from 9.5% to 25.2% with a higher number of INRs.. The achieved level of warfarin anticoagulation in this real-life setting is far below what is needed for effective long-term thromboprophylaxis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombosis; Warfarin; Young Adult

We previously demonstrated that the rational pediatric dosage of warfarin can be well-described by a SIZE parameter that includes an allometry exponent of weight. On the other hand, allometry alone is considered to be insufficient to predict drug clearance in neonates and infants. The primary purpose of the present study was to evaluate the effects of incorporation of the maturation process into the analysis model for the dose-response relationship of warfarin in Japanese children. In addition, we evaluated the effect of chronic heart failure (CHF) on the response to warfarin as an independent risk factor for increased anticoagulant effects.. Thirty-eight patients with stable anticoagulation by warfarin were enrolled. During a mean follow-up period of 4.74 ± 3.51 years, 1092 data points including prothrombin time-international normalized ratio (PT-INR) were obtained. The data were subjected to multiple regression analysis to identify covariates related to the anticoagulant effects.. Two different models describing the maturation process did not improve the predictive performance for the dose-response relationship in pediatric patients. In addition to the SIZE-normalized daily dose, the vitamin K epoxide reductase complex 1 (VKORC1) genotype, and concomitant use of bosentan, CHF was identified as a covariate increasing the anticoagulant effects of warfarin to 118%.. The SIZE parameter was useful even without incorporation of maturation models to describe the response to warfarin in pediatric patients, and our longitudinal follow-up study design with multiple observations was beneficial to detect changes within individual subjects.

Topics: Administration, Oral; Adolescent; Aging; Anticoagulants; Asian People; Blood Coagulation; Child; Child, Preschool; Chronic Disease; Dose-Response Relationship, Drug; Female; Genotype; Heart Failure; Humans; Infant; Male; Models, Biological; Vitamin K Epoxide Reductases; Warfarin

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Chronic Disease; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Male; Pyrazoles; Pyridines; Pyridones; Recurrence; Thiazoles; Treatment Outcome; Ultrasonography; Venous Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cerebral Infarction; Chronic Disease; Endarterectomy; Heparin; Humans; Hypertension, Pulmonary; Male; Parkinsonian Disorders; Postoperative Complications; Pyridines; Thiazoles; Treatment Outcome; Warfarin

Topics: Capsule Endoscopy; Chronic Disease; Gastrointestinal Hemorrhage; Humans; Intestine, Small; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary arterial hypertension (PAH) in which the pulmonary thrombus fails to resolve, resulting in occlusion and remodelling of pulmonary arteries.

Topics: Adult; Angiography; Anticoagulants; Chronic Disease; Dyspnea; Electrocardiography; Humans; Hypertension, Pulmonary; Male; Pulmonary Artery; Pulmonary Embolism; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and multiple chronic conditions (MCC) are unknown.. To determine whether there are differences in efficacy and safety of dabigatran, rivaroxaban, and warfarin regarding stroke prevention and bleeding rates, respectively, in elderly patients with AF with MCC.. This retrospective comparative effectiveness analysis included data from the population-based Medicare beneficiaries database, evaluating patients with new AF diagnosed from January 1, 2010, to December 31, 2013, who initiated an oral anticoagulant within 90 days of diagnosis. Patients with CHA2DS2-VASc scores of 1 to 3, 4 to 5, and 6 or higher; HAS-BLED scores of 0 to 1, 2, and 3 or higher; and Gagne comorbidity scores of 0 to 2, 3 to 4, and 5 or higher were categorized as having low, moderate, or high morbidity, respectively. Within morbidity categories, patients receiving dabigatran, rivaroxaban, or warfarin were matched using a 3-way propensity matching, and the relative hazards of stroke, major hemorrhage (MH), and death were evaluated. Data analysis included follow-up from the date of initial anticoagulant use through December 31, 2013.. Rivaroxaban (20 mg once daily), dabigatran (150 mg twice daily), or warfarin therapy.. Ischemic stroke, MH, and death.. The study cohort included 21 979 patients using dabigatran (mean [SD] age, 75.8 [6.4] years; 51.1% female), 23 177 using rivaroxaban (mean [SD] age, 75.8 [6.4] years; 49.9% female), and 101 715 using warfarin (mean [SD] age, 78.5 [7.2] years; 57.3% female). In the propensity-matched cohorts, there were no differences in stroke rates between the 3 oral anticoagulant groups. Dabigatran users had lower hazard of MH compared with warfarin users among patients with low MCC (hazard ratio [HR], 0.62; 95% CI, 0.47-0.83; P < .001; for MCC defined as low CHA2DS2-VASc score), and similar risk in patients with moderate to high MCC. While there was no difference in MH between rivaroxaban and warfarin users, rivaroxaban users had significantly higher MH risk compared with dabigatran users in the medium and high comorbidity groups (HR, 1.24; 95% CI, 1.04-1.48; P = .02 and HR, 1.28; 95% CI, 1.05-1.56; P = .01, respectively). Dabigatran and rivaroxaban users had lower rates of death compared with warfarin users (HR ranged from 0.52-0.84), across comorbidity levels.. Oral anticoagulants are similarly effective in stroke prevention among patients with AF with MCC. However, dabigatran and rivaroxaban use may be associated with lower rates of mortality in patients with MCC.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Comorbidity; Dabigatran; Female; Humans; Male; Proportional Hazards Models; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Topics: Adult; Age Distribution; Aged; Anticoagulants; Bosentan; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Incidence; Latvia; Male; Middle Aged; Phenylpropionates; Prevalence; Pulmonary Embolism; Pyrazoles; Pyridazines; Pyridones; Registries; Rivaroxaban; Sex Distribution; Sildenafil Citrate; Sulfonamides; Vasodilator Agents; Warfarin; Young Adult

The benefits and harms of oral anticoagulation therapy in patients with only one stroke risk factor (ie, CHA2DS2-VASc = 1 in males, or 2 in females) has been a subject of debate.. We analyzed all patients with only one stroke risk factor from the merged datasets of SPORTIF III and V trials. Anticoagulation control was defined according to time in therapeutic range (TTR).. Of the original trial cohort, 1097 patients had only one stroke risk factor. Stroke/systemic thromboembolic event had an incidence of 0.9 per 100 patient-years, with an incidence of 1.6 per 100 patient-years for all-cause death and 2.3%/patient-years for the composite outcome of stroke/systemic thromboembolic event/all-cause death. There were no significant differences in the risk for stroke/systemic thromboembolic event between sexes, nor between the different stroke risk factors amongst these atrial fibrillation patients with only one stroke risk factor. Cox regression analysis in patients treated with warfarin found only TTR to be inversely associated with stroke/systemic thromboembolic event (P = .034) and all-cause death (P = .015). Chronic heart failure was significantly associated with the outcome of all-cause death (P = .0019) and the composite outcome of stroke/systemic thromboembolic event/all-cause death (P = .021). There was a significant inverse linear association between TTR and the cumulative risk for both stroke/systemic thromboembolic event and all-cause death (both P <.001).. In atrial fibrillation patients with only one additional stroke risk factor (ie, CHA2DS2-VASc = 1 in males or 2 in females), rates of major adverse events (stroke/systemic thromboembolic event, mortality) were high, despite anticoagulation. TTR in warfarin-treated patients was inversely associated with the occurrence of both stroke/systemic thromboembolic event and all-cause death.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Azetidines; Benzylamines; Cause of Death; Chronic Disease; Comorbidity; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Mortality; Prognosis; Proportional Hazards Models; Risk Factors; Stroke; Thromboembolism; Warfarin

Topics: Aged; Anticoagulants; Atrial Appendage; Cardiomyopathy, Hypertrophic; Chronic Disease; Dyspnea; Echocardiography, Transesophageal; Heart Diseases; Heart Failure; Humans; Male; Thrombosis; Tomography, X-Ray Computed; Warfarin

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy.. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study.. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94).. There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted.. The authors have no conflict of interest.

Topics: Adult; Anticoagulants; Chronic Disease; Compression Bandages; Female; Humans; International Normalized Ratio; Male; Middle Aged; Postthrombotic Syndrome; Retrospective Studies; Varicose Ulcer; Warfarin; Wound Healing

Although generally recommended for atrial fibrillation (AF) in the general population, the efficacy and safety of warfarin in hemodialysis patients remains controversial. Warfarin use in hemodialysis patients may confer an additional risk of bleeding that is not appreciated in patients without renal failure because hemodialysis patients have platelet defects and receive anticoagulation agents during dialysis. The incidence of major bleeding was reported to be higher in Japanese AF patients on warfarin therapy compared to patients in other countries, suggesting that racial differences may influence bleeding tendency. Thus, examining risks and benefits of warfarin therapy in Japanese hemodialysis patients with AF is important.. In order to determine associations between warfarin use and new ischemic stroke events, major bleeding, and all-cause mortality, a prospective cohort study of 60 Japanese hemodialysis patients with chronic sustained AF was conducted using Cox proportional modeling and propensity score matching.. The mean patient age was 68.1 years. During 110 person-years of follow-up, 13 ischemic strokes occurred. After adjusting for CHADS2 score, warfarin use was not associated with a significant reduction in ischemic stroke events [hazard ratio (HR) 3.36; 95 % confidence interval (CI) 0.94-11.23]. Similar results were obtained after propensity score matching (HR 3.36; 95 % CI 0.67-16.66). Warfarin use was not associated with significant increases in major bleeding or all-cause mortality.. These results suggest that warfarin may not prevent ischemic stroke in Japanese hemodialysis patients with chronic sustained AF. Adequately powered studies are needed to determine the risks and benefits of anticoagulation therapy in these patients.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Chronic Disease; Female; Hemorrhage; Humans; Incidence; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Our aim was to identify risk factors for acute gastrointestinal (GI) bleeding in patients with myocardial infarction (MI) who were prescribed clopidogrel following hospital discharge.. Data were collected retrospectively from patients treated in Veteran Affairs hospitals in Ohio, USA, from 2001 to 2008 with a primary diagnosis of MI (International Classification of Diseases, 9th Revision) and a prescription for clopidogrel filled within 48 h of discharge. Primary outcome was acute GI bleeding after discharge.. Acute GI bleeding occurred in 107 of 3218 patients. Bleeding occurred in those who were elder (66.2 vs. 62.4 years, P = 0.0002), had lower glomerular filtration rate (74 vs. 81 mL/min, P = 0.024), had filled prescription for warfarin (15.9% vs. 6.9%, P = 0.0004), diagnosed as atrial fibrillation (20.6% vs. 11.1%, P = 0.003), chronic liver (5.6% vs. 2.2%, P = 0.018) or kidney disease (29.0% vs. 19.4%, P = 0.016). A risk model and GI bleed risk score were developed and showed that patients with age >65 years, use of warfarin, the presence of chronic liver or kidney disease were at increased risk for GI bleeding.. Veterans patients of advanced age, using warfarin and with chronic liver and kidney disease may be at increased risk of GI bleeding when prescribed clopidogrel following MI. A scoring system may help to identify patients at high risk for GI bleeding.

Topics: Acute Disease; Age Factors; Aged; Anticoagulants; Chronic Disease; Clopidogrel; Female; Gastrointestinal Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Ohio; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Ticlopidine; Veterans; Warfarin

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.

Topics: Aged; Amino Acids, Branched-Chain; Bilirubin; Biomarkers; Chronic Disease; Cysteine; Diabetes Mellitus; Diazepam; Female; Glycation End Products, Advanced; Humans; Liver Cirrhosis; Male; Middle Aged; Models, Molecular; Oxidation-Reduction; Oxidative Stress; Protein Binding; Renal Insufficiency; Serum Albumin; Spectrometry, Mass, Electrospray Ionization; Tryptophan; Warfarin

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin.. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001).. Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Chronic Disease; Creatinine; Female; Hemorrhage; Humans; Liver Diseases; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Serum Albumin; Treatment Outcome; Warfarin

Topics: Adult; Anticoagulants; Chronic Disease; Dyspnea; Edema; Endarterectomy; Female; Heparin; Humans; Hypertension, Pulmonary; Lower Extremity; Pulmonary Embolism; Recurrence; Respiratory Insufficiency; Thromboembolism; Warfarin

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Biomarkers; Chronic Disease; Drug Administration Schedule; Drug Monitoring; Fondaparinux; Humans; Male; Platelet Activation; Platelet Count; Polysaccharides; Predictive Value of Tests; Severity of Illness Index; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antihypertensive Agents; Bosentan; Chronic Disease; Diuretics; Drug Therapy, Combination; Humans; Hypertension, Pulmonary; Male; Pulmonary Embolism; Sulfonamides; Tomography, X-Ray Computed; Warfarin

To explore adherence with health regimens and factors influencing it of patients on warfarin therapy.. Adherence to health regimens is a crucial factor for patients on long-term warfarin therapy. Approximately 50% of patients with chronic conditions have good adherence. This study covers a more extensive perspective on patients' adherence to warfarin therapy than earlier studies, which focus mainly on adherence to medication.. A descriptive cross-sectional design was used.. A survey of 139 patients was conducted in 2008. A self-reported Adherence of people with Chronic Disease Instrument questionnaire was used to assess adherence to health regimens and factors influencing it. Chi-squared test, Mann-Whitney U-test and Kruskal-Wallis test were used to analyse the data.. About half (51%) of the respondents complied well with health regimens, while 74% had good adherence with warfarin therapy. Females had better adherence than males. The highest degree of adherence was reported by patients who had venous thrombosis and whose therapy had lasted from one to three years. Patients who adhered well to warfarin therapy also had good adherence with other health regimens such as diet, exercise, attending international normalised ratio tests and collaboration with health care. There was also a statistically significant difference between adherence to health regimens and motivation and sense of normality.. Good adherence to health regimens had an impact on good adherence to warfarin therapy. Collaboration with health care professionals, motivation and patients' sense of normality are crucial factors to improve adherence.. To improve adherence to health regimens, collaboration between patients and health professionals should be strengthened. Furthermore, discussion with patients can aid in understanding problems of motivation and help health care professionals provide support. Tailoring treatment and care as a part of patients' life helps them gain a sense of normality and improve adherence.

Topics: Aged; Anticoagulants; Chronic Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Patient Compliance; Surveys and Questionnaires; Warfarin

Essential thrombocytosis is extremely rare in children. However, when present, it is associated with increased prevalence of antiphospholipid antibodies and thrombo-hemorrhagic complications. The authors report here a child with Budd-Chiari Syndrome resulting from essential thrombocytosis and associated antiphospholipid antibodies. A 13- y-old boy presented with microcytic hypochromic anemia, hepatosplenomegaly and thrombocytosis. CT scan demonstrated calcified thrombus in inferior vena cava (IVC). Diagnosis of essential thrombocytosis was considered in view of persistent thrombocytosis, antiphospholipid antibodies, bone marrow showing increased number, clusters and giant forms of megakaryocytes and IVC thrombosis. He was started on warfarin prophylaxis and did not have thrombotic recurrence on follow up.

Topics: Adolescent; Anticoagulants; Antiphospholipid Syndrome; Budd-Chiari Syndrome; Chronic Disease; Developing Countries; Diagnosis, Differential; Humans; Male; Thrombocythemia, Essential; Tomography, X-Ray Computed; Warfarin

The benefits of taking of aspirin, clopidogrel, and warfarin in relation to cardiovascular mortality and re-hospitalization in chronic heart failure (HF) patients have been called into question. We examined the outcomes (cardiac mortality and/or HF re-hospitalization) in patients discharged from our hospital between January 2003 and July 2009 after hospitalization for chronic decompensated HF. Of 580 HF patients (mean age, 63 ± 13 years; mean ejection fraction, 26 ± 9%, 63% with coronary disease and 37% without coronary disease), 207 patients (36%) died due to cardiovascular reasons, and 313 (54%) required HF re-hospitalization for decompensated HF during a 39 ± 14 month follow-up period. 101 (17%) patients were taking clopidogrel during enrollment in the study. When comparing patients who were on clopidogrel treatment with those who were not, clopidogrel was found to have a beneficial effect on cardiac mortality (27 vs. 38%, P = 0.04). In conclusion, in this observational prospective study, patients who used clopidogrel showed decreased cardiac mortality [HR, 0.566 (95% CI 0.332-0.964), P = 0.036] compared to patients who did not take clopidogrel. Clopidogrel had a beneficial effect on the survival of chronic HF patients in the long term.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Chi-Square Distribution; Chronic Disease; Clopidogrel; Drug Interactions; Drug Utilization; Female; Health Care Surveys; Heart Failure; Humans; Male; Middle Aged; Patient Discharge; Patient Readmission; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke Volume; Ticlopidine; Time Factors; Turkey; Ventricular Function, Left; Warfarin

Medication nonadherence is a barrier to successfully managing hypertension, but little is known about the contribution that immediate discontinuations have on antihypertensive (AHT) nonadherence. The purpose of this study was to determine the proportion of new AHT users who discontinue after a single dispensation, and to examine potential predictors of these discontinuations.. This retrospective cohort study utilizing linked administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new AHT between 1994-2002. The primary end point was the proportion of subjects who discontinued their AHT after the first dispensation (first-fill discontinuation). The proportion of nonadherence attributed to first-fill discontinuations was then calculated. Multivariate regression identified factors associated with first-fill discontinuations.. 52,039 subjects were included in the analyses. Mean age was 59.4 (s.d. 12.5) years, and 42% were male. Overall, 25,812/52,039 (50%) subjects were nonadherent at 1 year; first-fill discontinuations accounted for 39.1% (10,081/25,812) of this nonadherence. Approximately 20% (10,081/52,039) of all subjects discontinued all AHT therapy after the first fill. A higher chronic disease score (adjusted odds ratio (OR) 1.09, 95% confidence interval (CI) 1.08-1.11) and antidepressant medication usage during the observation year (adjusted OR 1.17, 95% CI 1.09-1.26) was associated with increased risk for first-fill discontinuations. Older age, starting AHT therapy after 1994, frequent physician visits, or use of a statin, acetylsalicylic acid, warfarin or antihyperglycemic during the observation year was associated with a lower risk for first-fill discontinuations.. A substantial proportion of nonadherence to AHT medications is due to discontinuations after only a single dispensation.

Topics: Age Factors; Aged; Antidepressive Agents; Antihypertensive Agents; Aspirin; Chronic Disease; Depression; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Hypoglycemic Agents; Male; Medication Adherence; Middle Aged; Retrospective Studies; Saskatchewan; Warfarin

Persistently elevated antiphospholipid antibodies and positive lupus anticoagulant (LAC) are associated with an increased risk of thrombosis. The objective of this study was to explore whether antiphospholipid antibody and/or LAC positivity were associated with the traditional risk factors for thrombosis or with medication use in patients without autoimmune diseases hospitalised with arterial or venous thrombosis.. Cross-sectional study.. Montefiore Medical Center, a large urban tertiary care centre.. 270 patients (93 with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non-haemorrhagic stroke (cerebrovascular accident (CVA)) admitted between January 2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who had LAC and antiphospholipid antibodies measured within 6 months from their index admission. Patients with lupus or antiphospholipid syndrome were excluded.. The main dependent variable was antiphospholipid antibodies of 40 units or greater (antiphospholipid antibody positivity) and/or LAC positivity. Independent variables were traditional thrombosis risk factors, statin use, aspirin use and warfarin use.. 31 (11%) patients were LAC positive and/or antiphospholipid antibody positive. None of the traditional risk factors at the time of DVT/PE/CVA was associated with antiphospholipid antibody positivity. Current statin use was associated with an OR of 3.2 (95% CI 1.3 to 7.9, p=0.01) of antiphospholipid antibody positivity, adjusted for age, ethnicity and gender. Aspirin or warfarin use was not associated with antiphospholipid antibody levels.. If statin therapy reflects the history of previous hyperlipidaemia, high levels of antiphospholipid antibodies may be a marker for earlier endothelial damage caused by hyperlipidaemia.

Topics: Aged; Antibodies, Antiphospholipid; Aspirin; Biomarkers; Chronic Disease; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lupus Coagulation Inhibitor; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Stroke; Venous Thrombosis; Warfarin

Chronic spontaneous urticaria is a common condition, with a lifetime prevalence of 0.5-1.0%. It has a significant effect on quality of life, comparable to having triple-vessel coronary artery disease. Warfarin and nicoumalone are synthetic derivatives of the plant toxin coumarin. We report the first case of successful response to both warfarin and nicoumalone in the same patient, thereby demonstrating a class action of synthetic coumarins in the disease. Complete response with both coumarins occurred once an INR above 2.0 was achieved, and was maintained during a 12-month follow-up. The mechanism of action of coumarins on urticaria is not known, but may be related to decrease in thrombin production or to interference of activation of other inflammatory proteins produced during the coagulation process. Side-effects of anticoagulation can be catastrophic, and coumarin treatment currently remains reserved for restricted severe recalcitrant cases only.

Topics: Acenocoumarol; Administration, Oral; Chronic Disease; Dermatologic Agents; Female; Humans; International Normalized Ratio; Treatment Outcome; Urticaria; Warfarin; Young Adult

Endovenous ablation of great (GSV) and short saphenous vein (SSV) reflux has become the initial procedure for most patients with symptomatic venous insufficiency, and perforator ablation is increasingly used to assist in healing venous ulceration. Many patients have comorbid conditions, which require long-term anticoagulation with warfarin; however, the impact of a long-term anticoagulation therapy on endovenous ablation procedures is not understood. This study aims to determine the effects of chronic anticoagulation on the outcomes of endovenous ablation procedures in patients with chronic venous insufficiency (CVI).. Consecutive patients undergoing endovenous ablation for to Clinical severity (CEAP) class 2 through 6 CVI between January 1, 2005 and May 1, 2011 were evaluated; 781 patients with chronic venous reflux underwent 1,180 endovenous ablation procedures. We identified 45 patients receiving long-term anticoagulation therapy who underwent 71 endovenous ablation procedures, including 37 GSVs, 12 SSVs, and 22 perforator vein procedures. All patients underwent wound examination and duplex ultrasonography within 48 to 72 hours. Outcomes evaluated included closure rate and postoperative complications.. The mean age of the patients was 69.7 ± 13 years. Most patients treated presented with active venous ulceration (59% CEAP 6). Indications for anticoagulation included atrial fibrillation (n = 9, 20%), previous deep venous thrombosis (n = 16, 36%), hypercoagulable state (n = 9, 20%), prosthetic valve (n = 2, 4%), and others (n = 9, 20%). All patients receiving warfarin therapy (100%) underwent a postprocedure ultrasonography, which confirmed the successful closure of the GSVs and SSVs; successful initial perforator closure was achieved in 59% of patients (13/22). Repeat perforator ablation yielded a closure rate of 77%. Compared with a matched cohort group of 35 patients (61 perforators) undergoing perforator ablation without anticoagulation, treated during the same period, there was no significant difference in the rates of successful closure between the groups. No patients developed postoperative deep venous thrombosis or pulmonary embolus. No additional thrombotic complications were noted. Three patients (4.2%) developed a small hematoma after the procedure, which resolved with conservative treatment. No patients required postoperative hospital admission, and no postprocedure deaths occurred.. Based on our protocol, patients with severe CVI who were receiving long-term warfarin therapy can be treated safely and effectively with endovenous radiofrequency ablation for incompetent GSVs, SSVs, and perforator veins. Long-term warfarin therapy did not have a significant effect on perforator closure rates compared with no anticoagulation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Catheter Ablation; Chronic Disease; Drug Administration Schedule; Female; Humans; Los Angeles; Male; Middle Aged; Retrospective Studies; Saphenous Vein; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Insufficiency; Warfarin

The objective of this study was to evaluate the underlying diseases, thrombus localization, and other risk factors in pediatric patients with recurrent thrombosis in order to obtain a sense of early awareness of the possible recurrences. We retrospectively evaluated both inherited and acquired thrombophilic risk factors in children with recurrent thrombosis that were diagnosed and treated at Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors associated with recurrent thrombosis, and treatment modalities were analyzed in detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent thrombosis. Median age at first presentation in these 32 patients [11 women (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients had an underlying chronic disorder: the most common of which was congenital heart disease [n = 11 (34.4%)]. At presentation intracardiac localization, including the entrance of the inferior and superior vena cava, was observed in 10 of the patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients and at a different location in 17 (53%). Median time interval between the first and second episode of thrombosis was 6.5 months (range: 1-180 months). Considering both acquired and congenital thrombophilic factors, three (9.3%) patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and three risk factors, respectively. More than half of the patients had elevated plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was performed in three patients with organized, chronic intracardiac thrombus. Tissue plasminogen activator (t-PA) was used more frequently to treat recurrence than the first event (15.6 vs. 28.1%) and consequently the complete resolution rate was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11 of the patients during the initial episode and in 10 patients during recurrence (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin (n = 1)]. In total, four patients (12.5%) died because of their underlying disorders and six (18.7%) developed postthrombotic syndrome during the follow-up. Recurrent thrombosis should be expected, especially in cases with congenital heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-d

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Child; Child, Preschool; Chronic Disease; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Heart Defects, Congenital; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Postthrombotic Syndrome; Recurrence; Retrospective Studies; Risk Factors; Thrombectomy; Thrombophilia; Thrombosis; Tissue Plasminogen Activator; Warfarin

Evidence-based guidelines should in most cases be followed also in the treatment of elderly. Older people are often suboptimally treated with the recommended drugs.. To describe how well general practitioners adhere to current guidelines in the treatment of elderly with cardiovascular disease and evaluate local education as a tool for improvement.. Data was collected from the medical records of patients aged ≥ 65, who visited a primary health care center in Sweden 2006 and had one or more of the following diagnoses: hypertension, ischemic heart disease, heart failure, chronic atrial fibrillation, or prior stroke. Local education was organized and included feed-back to the patient's doctor and discussion about regional guidelines. Repeated measurements were performed in 2008.. The adherence to guidelines was low. Approximately one-third of the patients with hypertension reached target blood pressure, stroke patients more often. More patients with heart failure were treated with angiotensin converting enzyme inhibitor than in other European countries, but still only 60%. Half of the patients with chronic atrial fibrillation were treated with Warfarin, although more than two-thirds had a CHADS(2) score indicating the need. Educational efforts appeared to increase the adherence and hence should be encouraged.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Pressure; Cardiovascular Diseases; Chronic Disease; Evidence-Based Practice; General Practice; General Practitioners; Guideline Adherence; Heart Failure; Humans; Hypertension; Patient Compliance; Stroke; Warfarin

As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).. A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993-2008 was conducted within the United Kingdom General Practice Research Database. A nested case-control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).. The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (-0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (-0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.. Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Databases, Factual; Female; General Practice; Humans; Intracranial Hemorrhages; Logistic Models; Male; Odds Ratio; Platelet Aggregation Inhibitors; Preventive Health Services; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; United Kingdom; Warfarin

Anticoagulation is a challenge for the prophylaxis of thromboembolic events in elderly patients with chronic atrial fibrillation. Stable anticoagulation is defined as the time within >70% of the therapeutic range. However, the dosage required to achieve stable anticoagulation remains unknown. The aim of this study was to analyze the warfarin dose necessary for the maintenance of stable oral anticoagulation therapy in elderly patients.. We analyzed 112 consecutive outpatients with atrial fibrillation who were >65 years of age, had received anticoagulation therapy with warfarin for more than 1 year and had a stable international normalized ratio between 2.0 and 3.0 for >6 months. The international normalized ratio was measured in the central laboratory using the traditional method.. The patients were stratified according to the following age groups: <75 or >75 years and <80 or >80 years. The mean daily doses of warfarin were similar for patients <75 or >75 years (3.34+1.71 versus 3.26 +1.27 mg/ day, p = 0.794) and <80 or >80 years (3.36+ 1.49 versus 3.15 + 1.23 mg/day, p = 0.433). In 88 (79%) patients, the daily warfarin dose was between 2 and 5 mg/day; in 13 (11%) patients, the daily warfarin dose was <2.0 mg/day; and in 11 (10%) patients, the daily warfarin dose was >5.0 mg/day. The correlation between the daily warfarin dose and the international normalized ratio was 0.22 (p = 0.012).. Stable anticoagulation was achieved in 80% of patients who received doses of 2 to 5 mg/day of warfarin, and the mean daily dose was similar across the age groups analyzed.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Chronic Disease; Female; Humans; International Normalized Ratio; Male; Reference Values; Time Factors; Treatment Outcome; Warfarin

Guidelines for perioperative warfarin management in patients with venous thromboembolic disease (VTE) are largely based on expert opinion.. To assess the effectiveness and safety of a conservative perioperative anticoagulation strategy in patients with VTE on chronic warfarin therapy. Our center uses a conservative bridging approach for chronic VTE patients consisting of withholding warfarin for 5 days preoperatively, with prophylactic low-molecular-weight heparin (LMWH) post-procedure only if patients are admitted to hospital.. We performed a single-center retrospective cohort study. During the study period (1997-2011) there were 634 procedures in 416 patients that were reviewed for postoperative outcomes at 30 and 90 days.. Of the 634 procedures, 156 procedures (24.6%) were completed as inpatients. Pre- and post-procedure LMWH bridging was used in 15 (2.4%) and 152 (24.0%) of all procedures, respectively. The 30-day VTE incidence was 0.32% (95% confidence interval [CI] 0.087-1.14), all non-fatal DVTs. The 30-day incidence of major and total bleeding events was 1.26% (95% CI 0.64-2.47) and 3.00% (95% CI 1.93-4.63), respectively. The all-cause mortality rate was 0.32% (95% CI 0.087-1.14) at 30 days; two patients died from arterial thrombosis events.. A randomized controlled trial is needed to provide definitive conclusions but a conservative bridging approach appears promising.

Topics: Aged; Anticoagulants; Chronic Disease; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Inpatients; Male; Middle Aged; Perioperative Period; Postoperative Period; Retrospective Studies; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

Topics: Aged, 80 and over; Anemia; Atrial Fibrillation; Chronic Disease; Erythema; Esophagitis, Peptic; Female; Humans; Iron, Dietary; Practice Patterns, Physicians'; Warfarin

To evaluate the initial clinical safety and feasibility of anticoagulation using warfarin for Budd-Chiari syndrome (BCS) with chronic inferior vena cava (IVC) thrombosis.. Between October 2005 and June 2009, a total of 16 consecutive BCS patients with chronic IVC thrombosis were treated with warfarin. Warfarin was administered orally at 2.5 mg/d for approximately 3-12 months. Transluminal balloon dilatation of the IVC with a 30-mm balloon catheter was applied for the patients with complete resolution of the thrombus. Data relating to the technical success, angiographic results, complications, and final clinical outcome were collected retrospectively and follow-ups were performed at 1, 3, 6, and 12 months after the stent placement, and annually thereafter.. Warfarin was successfully used for anticoagulation in all patients without any complications. Patients were followed up as outpatients for 6.43 ± 2.19 months, and in 14 cases, complete disappearance of the thrombosis was achieved with successful treatment by balloon dilation. In two patients with partial resolution of the thrombosis, Z-stent placement was initiated to compress the thrombus to prevent migration of the thrombosis, followed by dilation of the IVC. During the follow-up for 20.94 ± 10.31 months after the procedure, all the IVC remained patent without complications or pulmonary embolus, and all patients were alive with resolution of symptoms at the time of this study.. The use of warfarin for anticoagulation proved to be simple, safe, and feasible for BCS with chronic IVC thrombosis.

Topics: Administration, Oral; Adult; Anticoagulants; Budd-Chiari Syndrome; Catheterization; China; Chronic Disease; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phlebography; Retrospective Studies; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vascular Patency; Vena Cava, Inferior; Warfarin; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Warfarin

Bucolome, a nonsteroidal antiinflammatory drug, enhances the effects of warfarin. In the present study, the effects of combination therapy (bucolome+warfarin) vs. warfarin alone on atrial fibrillation were investigated.. Combined therapy resulted in a decrease in the warfarin dose to approximately one-third. The fluctuations of the international normalized ratio and the time in therapeutic range were similar in both groups. There was no adverse effect in either group. Interestingly, uric acid was lower in the bucolome group.. Bucolome enhanced the effects of warfarin, resulting in a decreased dose of warfarin without adverse effects and it showed similar anticoagulant stability to warfarin alone.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Atrial Fibrillation; Barbiturates; Blood Coagulation; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; International Normalized Ratio; Japan; Male; Middle Aged; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Warfarin is often used in patients with systolic heart failure (HF) to prevent adverse outcomes. However, its long-term effect remains controversial. The objective of this study was to determine the association of warfarin use and outcomes in patients with advanced chronic systolic HF without atrial fibrillation (AF), previous thromboembolic events, or prosthetic valves. Of the 2,708 BEST patients, 1,642 were free of AF without a history of thromboembolic events and without prosthetic valves at baseline. Of these, 471 patients (29%) were receiving warfarin. Propensity scores for warfarin use were estimated for each patient and were used to assemble a matched cohort of 354 pairs of patients with and without warfarin use who were balanced on 62 baseline characteristics. Kaplan-Meier and Cox regression analyses were used to estimate the association between warfarin use and outcomes during 4.5 years of follow-up. Matched participants had a mean age ± SD of 57 ± 13 years with 24% women and 24% African-Americans. All-cause mortality occurred in 30% of matched patients in the 2 groups receiving and not receiving warfarin (hazard ratio 0.86, 95% confidence interval 0.62 to 1.19, p = 0.361). Warfarin use was not associated with cardiovascular mortality (hazard ratio 0.97, 95% confidence interval 0.68 to 1.38, p = 0.855), or HF hospitalization (hazard ratio 1.09, 95% confidence interval 0.82 to 1.44, p = 0.568). In conclusion, in patients with chronic advanced systolic HF without AF or other recommended indications for anticoagulation, prevalence of warfarin use was high. However, despite a therapeutic international normalized ratio in those receiving warfarin, its use had no significant intrinsic association with mortality and hospitalization.

Topics: Adult; Algorithms; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Chronic Disease; Confidence Intervals; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Valve Prosthesis; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Regression Analysis; Thromboembolism; Treatment Outcome; Warfarin

Topics: Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Bicuspid; Chronic Disease; Dental Caries; Epistaxis; Female; Follow-Up Studies; Humans; Incisor; International Normalized Ratio; Male; Middle Aged; Molar, Third; Oral Hemorrhage; Polypharmacy; Postoperative Complications; Tooth Extraction; Warfarin

An acute increase in the international normalized ratio (INR; a comparison of prothrombin time to monitor the effects of warfarin) over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine (SC) and an accelerated progression of CKD. Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. We termed this warfarin-related nephropathy (WRN), and previously reported cases of WRN only in patients with CKD. We now assess whether this occurs in patients without CKD, its risk factors, and consequences. In 15,258 patients who initiated warfarin therapy during a 5-year period, 4006 had an INR over 3 and SC measured at the same time; however, the large data set precluded individual patient clinical assessment. A presumptive diagnosis of WRN was made if the SC increased by over 0.3 mg/dl within 1 week after the INR exceeded 3 with no record of hemorrhage. WRN occurred in 20.5% of the entire cohort, 33.0% of the CKD cohort, and 16.5% of the no-CKD cohort. Other risk factors included age, diabetes mellitus, hypertension, and cardiovascular disease. The 1-year mortality was 31.1% with compared with 18.9% without WRN, an increased risk of 65%. Thus, WRN may be a common complication of warfarin therapy in high-risk patients and CKD doubles this risk. The mechanisms of these risks are unclear.

Topics: Biopsy; Chronic Disease; Erythrocyte Aggregation; Humans; International Normalized Ratio; Kidney Diseases; Kidney Tubules, Proximal; Mortality; Risk Factors; Warfarin

Topics: Anticoagulants; Australia; Chronic Disease; Evidence-Based Nursing; General Practice; Humans; Nursing Records; Primary Health Care; Safety Management; Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Autoantibodies; Chronic Disease; Female; Humans; Leg Dermatoses; Phosphatidylserines; Prothrombin; Skin Diseases, Vascular; Warfarin

The International Normalised Ratio (INR)/International Sensitivity Index (ISI) system was developed as a way to standardise the prothrombin time during the monitoring of patients undergoing oral anti-coagulant therapy with vitamin K antagonists. The wide acceptance of the INR has led to its use as one of three parameters used in the Model for End stage Liver disease (MELD) scoring system to aid the prioritisation of patients for liver transplant. Literature published recently has highlighted the potential inadequacy of the INR system in this context. Our aim was to investigate the degree of difference between INR values calculated using an ISI derived from warfarinised patients and those calculated using an ISI derived from patients with liver disease. Prothrombin times from 60 patients with liver disease were determined using three working thromboplastin reagents; Innovin, Thromborel S and Thromboplastin C and two reference thromboplastins; rTF/95 and RBT/05. All thromboplastin reagents tested had standard international sensitivity indices (ISIs) assigned following calibration with patients on oral anticoagulant therapy (ISIvka). As a result of the new calibration each of the working thromboplastin reagents was assigned a specific "liver patient" ISI. Two INR values were calculated for each thromboplastin patient involved in the calibration. A comparison of the mean INRliver with INRvka showed a statistically significant difference between the two values (p<0.0001). A similar relationship existed for INRs on a further 20 patients with liver disease whose plasmas were not used to derive the ISIliver. This difference led to a change in the final MELD score and could therefore affect the prioritisation and management of these patients.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Blood Coagulation; Calibration; Chronic Disease; Humans; International Normalized Ratio; Liver; Liver Diseases; Liver Transplantation; Predictive Value of Tests; Prothrombin Time; Recombinant Proteins; Severity of Illness Index; Thromboplastin; Warfarin

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

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

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown.. We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33,165 person-years off anticoagulation among 10,908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate > or =60 mL x min(-1) x 1.73 m(-2): relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL x min(-1) x 1.73 m(-2) and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2) (P=0.0082 for trend).. Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; California; Chronic Disease; Comorbidity; Creatinine; Female; Fibrinolytic Agents; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria; Risk Factors; Stroke; Thromboembolism; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Female; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk; Stroke; Time Factors; Warfarin

The objective of this study was to evaluate the rate of stroke associated with aspirin and warfarin in routine clinical practice. The study included patients aged 40+ with chronic atrial fibrillation (cAF) registered in the UK General Practice Research Database. The outcome was the rate of stroke during current, past and no use of aspirin and warfarin. The study included 51,807 cAF patients. There was no difference in the rate of stroke between current and past use of aspirin (relative rate [RR] = 1.04 [95% confidence interval (CI) 0.94 - 1.15]), while the rate of stroke was reduced during current warfarin use compared to past use (RR = 0.62 [95% CI 0.54 - 0.71]). For warfarin, a pattern of lower rates of stroke during current exposure and higher rates with past exposure was seen only in patients treated for at least 6-12 months. For aspirin, no changes in the rates of stroke were observed with discontinuation of aspirin. The effectiveness of warfarin was dependent on the level of anticoagulation, with optimal risk reduction occurring within the recommended international normalised ratio (INR) range of 2.0 to 3.0. The proportion of patients achieving a stable INR within the target therapeutic range was at its lowest during the first three months of warfarin treatment. In conclusion, the results of this study support the effectiveness of warfarin treatment to reduce the rate of stroke in cAF patients in the general clinical practice setting, however the risk reduction is lower than that reported in clinical trials.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Risk Factors; Stroke; Time Factors; United Kingdom; Warfarin

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Chronic Disease; Combined Modality Therapy; Disease Progression; Electric Countershock; Female; Heart Rate; Humans; Kidney Diseases; Risk Factors; Stroke; Stroke Volume; Warfarin

To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk.. A prospective multicentre registry.. In hospital, after discharge and follow-up by telephone call.. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included.. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk.. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Chronic Disease; Clopidogrel; Coronary Disease; Disease-Free Survival; Drug Therapy, Combination; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Stents; Thromboembolism; Ticlopidine; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Chronic Disease; Embolism; Humans; Risk Assessment; Stroke; Time Factors; Treatment Outcome; Warfarin

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

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

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Chronic Disease; Clopidogrel; Death; Double-Blind Method; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Stroke; Stroke Volume; Ticlopidine; Warfarin

An 80-year old woman presented with macroscopic hematuria on June 4(th), 2008. She had been suffering from general malaise and appetite loss since about 10 days previously. She had received anticoagulant therapy with warfarin due to chronic atrial fibrillation and PT-INR was well controlled between 1.6-2.2. When she presented, PT-INR was 12.88, and urinary tract infection (UTI) and hypoalbuminemia (2.2 g/dl) were observed. Therefore, warfarin therapy was discontinued, and antibiotics and vitamin K were administered. Normalization of PT-INR resulted in the disappearance of hematuria and UTI improved as a result of antibiotics administration. As the appetite loss improved, for serum albumin level increased. The previous dose of warfarin achieved PT-INR around 1.8. Her drug compliance had been good, and she took no drug nor food which could interact with warfarin. We also found no liver dysfunction, acute renal failure, malignancy, nor hyper- or hypo-thyroidism. Hypoalbuminemia caused by appetite loss due to UTI seems very likely to increase concentration of circulating free warfarin resulting in extreme prolongation of PT-INR. Our findings in the present case may suggest that we should pay more attention on changes of drug pharmacokinetics in elderly patients because of their poor adaptation to their circumstances such as infection or dehydration.

Topics: Aged, 80 and over; Anorexia; Atrial Fibrillation; Chronic Disease; Female; Humans; Prothrombin Time; Urinary Tract Infections; Warfarin

Practice guidelines recommend long-term stroke prophylaxis in patients with chronic atrial fibrillation (cAF).. To examine treatment initiation and persistence and factors that influence the choice of cAF treatment.. This study used the General Practice Research Database, including computerized medical records of general practitioners in the UK. Patients aged 40+ years with cAF after 1 January 2000 were included. Cox proportional hazards regression models evaluated initiation and treatment continuation over time of warfarin and aspirin. Treatment discontinuation was defined as no repeat prescription within a three-month period after the expected end of the treatment course.. The study population included 41 910 cAF patients. Elderly patients (aged 85+) were less likely to start warfarin [relative rate (RR) = 0.16, 95% confidence interval (CI) 0.15-0.18] and more likely to start aspirin (RR = 1.66, 95% CI 1.47-1.88) than patients aged 40-64 years. A history of dementia (RR = 0.28, 95% CI 0.17-0.44) and falls (RR = 0.76, 95% CI 0.70-0.83) also reduced the likelihood of warfarin initiation. Adjusting for age and gender, higher stroke risk (CHADS2 score) was not found to be associated with initiation of warfarin or aspirin contrary to current guidelines recommendations. One-year persistence was 70% for warfarin and 50% for aspirin. Treatment persistence was higher in elderly patients using warfarin and aspirin. A higher CHADS(2) score was associated with improved persistence only with warfarin.. The low likelihood of patients with cAF in general practice remaining on treatment long-term indicates that not all benefits as observed in clinical trials may be achieved in usual clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Stroke; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Aortic Valve; Chronic Disease; Female; Gastric Antral Vascular Ectasia; Heart Valve Prosthesis; Humans; Laser Coagulation; Thromboembolism; Warfarin

Nutritional deficiencies due to malabsorption occur after major gastric resection, and drugs that are primarily absorbed in the stomach or duodenum also are likely to exhibit decreased absorption. However, we performed a MEDLINE search (1960-2007) and found no evidence in the literature regarding the specific effects of warfarin absorption after total gastrectomy with Roux-en-Y gastric bypass procedure. We describe a 71-year-old woman receiving warfarin therapy for chronic atrial fibrillation who underwent a completion gastrectomy and Roux-en-Y esophagojejunostomy for an invasive adenocarcinoma of her gastric remnant. Before surgery, her international normalized ratio (INR) had been stable in her target range of 2-3 with warfarin 5-6 mg/day. At the time of her admission for the surgery, however, her INR was subtherapeutic at 1.73; warfarin was discontinued, and heparin and, subsequently, enoxaparin were used throughout her admission. After the surgery, the patient was discharged to a skilled nursing facility to continue bridge therapy with enoxaparin while warfarin was restarted and adjusted to a therapeutic INR of 2-3. Three months after discharge, the patient was hospitalized again for shortness of breath and was found to have an INR of 1.30 on admission, despite good compliance with her drugs. During this admission, the patient demonstrated resistance to warfarin therapy, requiring doses up to 20 mg/day to reach a therapeutic INR. To our knowledge, this is the first case report to demonstrate that patients undergoing a complete gastric resection followed by a Roux-en-Y gastric bypass procedure may display warfarin resistance. Close monitoring and dosage adjustment may be necessary to maintain therapeutic anticoagulation in these patients.

Topics: Adenocarcinoma; Aged; Atrial Fibrillation; Chronic Disease; Drug Resistance; Esophagus; Female; Gastrectomy; Gastric Bypass; Humans; International Normalized Ratio; Jejunum; Stomach Neoplasms; Warfarin

Perioperative management of bariatric surgical patients receiving chronic anticoagulation requires an understanding of potential hemorrhagic and thromboembolic risks. The aim of this study is to evaluate hemorrhagic and thromboembolic complications in morbidly obese patients who are on oral anticoagulation treatment and subsequently undergo laparoscopic bariatric surgery.. The medical records of all laparoscopic Roux-en-Y gastric bypass (LRYGB) patients from June 2001 to March 2006 were retrospectively reviewed. In addition, data of patients who received chronic anticoagulation therapy with Coumadin and underwent laparoscopic Roux-en-Y gastric bypass was analyzed. Clinical parameters included length of hospitalization, hemorrhagic complications, thromboembolic complications, conversion rate, reoperation, and blood transfusion.. During the study period, 1,700 consecutive patients underwent bariatric surgery for the treatment of morbid obesity. Of these, 21 patients were treated with chronic oral anticoagulation; 3 of the 21 (14%) had hemorrhagic complications: one patient had intraluminal hemorrhage and two patients had intraabdominal hemorrhage. Two patients required blood transfusion, and one patient underwent surgical reintervention. None of the 21 laparoscopic operations were converted to open procedures. There were no postoperative mortalities, and there were no thromboembolic events in this series.. Laparoscopic bariatric surgery can be performed relatively safely in morbidly obese patients who are treated with chronic oral anticoagulation. Even in the presence of bleeding, patients can be successfully treated without the need for reoperation.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Chronic Disease; Gastric Bypass; Hemorrhage; Humans; Laparoscopy; Obesity, Morbid; Retrospective Studies; Thromboembolism; Time Factors; Warfarin

The incidence of stroke in patients with atrial fibrillation (AF) can be significantly reduced with warfarin therapy especially if optimally controlled.. To evaluate the effect of the interval between consecutive prothrombin time measurements on the time in therapeutic range (INR 2-3) in a cohort of patients with AF on chronic warfarin treatment in the community.. All INR measurements available from a relatively large cohort of patients with chronic AF were reviewed and the mean interval between consecutive INR tests of each patient was correlated with the time in therapeutic range (TTR).. Altogether 251,916 INR measurements performed in 4408 patients over a period of seven years were reviewed. Sixty percent of patients had their INR measured on average every 2 to 3 weeks and most others were followed at intervals of 4 weeks or longer. A small proportion (3.6%) had their INR measured on average every week. A significant decline in the time in therapeutic range was observed as the intervals between tests increased. At one to three weeks interval the TTR was 48%, at 4 weeks interval 45% and at 5 weeks 41% (P<0.0005). A five percent increment in TTR was observed if more tests were performed at multiplications of exactly 7 days (43% vs 48% P<0.0001).. A better control with an increase in the TTR was observed in patients with atrial fibrillation if prothrombin time tests are performed at regular intervals of no longer than 3 weeks.

Topics: Administration, Oral; Analysis of Variance; Anticoagulants; Atrial Fibrillation; Chronic Disease; Cohort Studies; Humans; International Normalized Ratio; Prothrombin Time; Time Factors; Warfarin

The natural history of chronic portomesenteric (PM) and portosplenomesenteric (PSM) venous thrombosis is defined poorly. Therapeutic options are limited, and are directed at the prevention of variceal bleeding and the control of abdominal pain related to gastrointestinal hyperemia.. Patients with extensive PM and PSM thrombosis were reviewed retrospectively to evaluate the efficacy of medical therapy and to determine which clinical variables had prognostic significance regarding long-term survival.. Sixty patients, with a median age at diagnosis of 44 years (range, 18-68 y), were assessed. The median follow-up period was 3.5 years (range, 0.2-32.0 y). The overall survival rate was 73.3%, with 1- and 5-year survival rates of 81.6%, and 78.3%, respectively. One- and 5-year survival rates, excluding patients who died from malignancy-related causes, were 85.7% and 82.1%, respectively. Factors associated with improved survival included treatment with beta-blockers (P = .02; odds ratio [OR], .09; 95% confidence interval [CI], 0.01-0.70) and anticoagulation (P = .005; OR, 0.01; 95% CI, <0.01 to 0.26). Eighteen patients in total were anticoagulated, including 8 patients who had variceal bleeding, all of whom underwent endoscopic band ligation of esophageal varices before anticoagulation. By using Cox regression analysis, variables associated with reduced survival were the presence of ascites (P = .001; OR, 42.6; 95% CI, 5.03-360), and hyperbilirubinemia (P = .01; OR, 13.8; 95% CI, 1.9-100) at presentation. Six patients died of variceal hemorrhage.. Patients with chronic PM and PSM venous thrombosis without underlying malignancy have an acceptable long-term survival. Treatment with beta-blockers and anticoagulation appears to improve outcome.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Anticoagulants; Ascites; Chronic Disease; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Hyperbilirubinemia; Ligation; London; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Multivariate Analysis; Serum Albumin; Survival Rate; Venous Thrombosis; Warfarin

Warfarin is used for the prevention of stroke in chronic atrial fibrillation. The product has a narrow therapeutic index and to obtain treatment success, patients must be maintained within a given therapeutic range (International Normalised Ratio;INR). To ensure a wise allocation of health care resources, scrutiny of costs associated with various treatments is justified. The objective of this study was to estimate the health care cost of INR controls in patients on warfarin treatment with chronic atrial fibrillation in primary care in Sweden.. Data from various sources were applied in the analysis. Resource consumption was derived from two observational studies based on electronic patient records and two Delphi-panel studies performed in two and three rounds, respectively. Unit costs were taken from official databases and primary health care centres.. The mean cost of one INR control was SEK 550. The mean costs of INR controls during the first three months, the first year and during the second year of treatment were SEK 6,811, SEK 16,244 and SEK 8,904 respectively.. INR controls of patients on warfarin treatment in primary care in Sweden represent a substantial cost to the health care provider and they are particularly costly when undertaken in home care. The cost may however be off-set by the reduced incidence of stroke.

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Drug Monitoring; Health Care Costs; Humans; International Normalized Ratio; Prevalence; Primary Health Care; Stroke; Sweden; Time Factors; Warfarin

To report a case in which the anticoagulation effect of warfarin appeared to have been potentiated by chitosan, probably due to interference with the absorption of vitamin K.. An 83-year-old male with hypertensive cardiovascular disease, type 2 diabetes mellitus, and chronic atrial fibrillation complicated by left atrial thrombus formation was maintained on warfarin 2.5 mg/day. Marked elevation of the international normalized ratio (INR) was noticed after self-medication with chitosan 1200 mg twice daily. He denied taking any other drugs, natural substances, herbal medicines, and nutritional supplements, and stated that he had not changed his dietary habits. After parenteral administration of vitamin K and discontinuation of chitosan, the INR returned to within the target range. However, the patient took chitosan again, and the INR increased to well above the target range. Following strong medical advice, the patient stopped taking chitosan, and the INR remained stable thereafter.. Chitosan is a positively charged polymer that binds to the negatively charged lipids and bile acids in the gastrointestinal tract. It can affect the absorption of vitamins A, D, E, and K. Therefore, the anticoagulation effect of warfarin may be potentiated by chitosan through this mechanism. Use of the Naranjo probability scale revealed that the adverse effect was probably due to chitosan.. The interaction between warfarin and chitosan has not previously been reported. Healthcare professionals should be aware of this potential interaction.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chitosan; Chronic Disease; Diabetes Mellitus, Type 2; Drug Synergism; Humans; Hypertension; International Normalized Ratio; Male; Self Medication; Thrombosis; Vitamin K; Vitamins; Warfarin

Deep venous thrombosis (DVT) is common, but only 2%-4% of DVTs involve the upper extremities (Roos in Am J Surg 154:568-73, 1987). Upper extremity DVT has a primary or secondary cause, and primary thrombosis is much rarer than secondary thrombosis. Primary upper extremity DVT comprises effort venous thrombosis and idiopathic thrombosis. Effort subclavian venous thrombosis, also called Paget-Schroetter syndrome, is an uncommon entity, which usually develops after strenuous effort of the upper extremities. Effort thrombosis of the upper extremity has been described in athletes involved in a wide variety of sports, including ball games, combatant sport and heavy athletics, games with rackets or clubs, and aquatic sports (Zell et al. in Angiology 52:337-42, 2001). Push-up exercise is a strengthening exercise for building up strength and endurance in the muscles of the upper arm and shoulders. It is also considered to be a core exercise in shoulder rehabilitation programs to activate the serratus anterior muscle in people with shoulder dysfunction (Ludewig et al. in J Sports Med 32:484-93, 2004). We report what to our knowledge is the first case of effort DVT of an upper extremity caused by push-up exercise.

Topics: Adult; Anticoagulants; Chronic Disease; Exercise Therapy; Female; Follow-Up Studies; Headache; Humans; Phlebography; Subclavian Vein; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Beta-blockers have many different physiologic effects that could potentially influence the risk of hemorrhagic events in chronic heart failure patients (CHF) on warfarin. We examined how different beta-blockers vary in their associated risk of a hemorrhagic event.. We used databases from the Department of Veterans Affairs (VA) that contain information on medications prescribed, diagnoses, and hospitalizations. We identified patients with CHF on warfarin and either metoprolol, carvedilol, atenolol, or no beta-blocker during 1999-2001. We modeled time to first hemorrhagic event using a Cox proportional hazards model, adjusting for age, ethnicity, comorbidities, and other factors. INR levels were examined in a subsample of 3546 patients.. We identified 66,988 CHF patients on warfarin. Hemorrhagic events occurred in 15.3% of the sample and, in 3.8% of the sample, the hemorrhage was considered severe. Compared to patients on carvedilol, the hazards ratio for a new hemorrhagic event was 1.25 (1.17, 1.34) for no beta-blocker, 1.27 (1.18, 1.38) for atenolol, and 1.38 (1.28, 1.48) for metoprolol. No differences in INR levels were evident among the four groups.. The risk for a hemorrhagic event among CHF patients on warfarin may be affected by beta-blocker use and varies depending on which beta-blocker is prescribed.

Topics: Adrenergic beta-Antagonists; Adverse Drug Reaction Reporting Systems; Aged; Anticoagulants; Atenolol; Carbazoles; Carvedilol; Chi-Square Distribution; Chronic Disease; Drug Therapy, Combination; Drug Utilization; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Male; Metoprolol; Middle Aged; Pharmacoepidemiology; Practice Patterns, Physicians'; Propanolamines; Proportional Hazards Models; Risk Factors; Time Factors; United States; United States Department of Veterans Affairs; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Chemoprevention; Chronic Disease; Heart Valve Prosthesis; Heparin; Humans; Perioperative Care; Risk Assessment; Thromboembolism; Warfarin

Recent trials have found that ximelagatran and warfarin are equally effective in stroke prevention for patients with atrial fibrillation. Because ximelagatran can be taken in a fixed, oral dose without international normalized ratio monitoring and may have a lower risk of hemorrhage, it might improve quality-adjusted survival compared with dose-adjusted warfarin.. To compare quality-adjusted survival and cost among 3 alternative therapies for patients with chronic atrial fibrillation: ximelagatran, warfarin, and aspirin.. Semi-Markov decision model.. Hypothetical cohort of 70-year-old patients with chronic atrial fibrillation, varying risk of stroke, and no contraindications to anticoagulation therapy.. Quality-adjusted life-years (QALYs) and costs in US dollars.. For patients with atrial fibrillation but no additional risk factors for stroke, both ximelagatran and warfarin cost more than 50,000 dollars per QALY compared with aspirin. For patients with additional stroke risk factors and low hemorrhage risk, ximelagatran modestly increased quality-adjusted survival (0.12 QALY) at a substantial cost (116,000 dollars per QALY) compared with warfarin. For ximelagatran to cost less than 50,000 dollars per QALY it would have to cost less than 1100 dollars per year or be prescribed to patients who have an elevated risk of intracranial hemorrhage (>1.0% per year of warfarin) or a low quality of life with warfarin therapy.. Assuming equal effectiveness in stroke prevention and decreased hemorrhage risk, ximelagatran is not likely to be cost-effective in patients with atrial fibrillation unless they have a high risk of intracranial hemorrhage or a low quality of life with warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Azetidines; Benzylamines; Chronic Disease; Cost-Benefit Analysis; Decision Support Techniques; Humans; Prodrugs; Quality-Adjusted Life Years; Stroke; United States; Warfarin

This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients.. A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis.. Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749).. The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.

Topics: Atrial Fibrillation; Chronic Disease; Cohort Studies; Humans; Insurance Claim Review; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Warfarin

Retropharyngeal haematomas (RPHs) are rare but potentially life-threatening conditions that require a prompt diagnosis. However, the clinical scenario is not always straightforward as their presentation may be insidious, with no specific signs or symptoms. Treatment of RPH is conservative in the majority of cases, with close observation. Nevertheless, surgical intervention is sometimes indicated for large, non-resolving haematomas. We present the case of a 53-year-old woman on anticoagulant therapy who required evacuation of a traumatic RPH. We also propose a clinical protocol for the management of these entities according to our experience and previous literature reports.

Topics: Accidental Falls; Anticoagulants; Aortic Valve; Chronic Disease; Diagnosis, Differential; Drainage; Heart Valve Prosthesis; Hematoma; Humans; Male; Mediastinum; Middle Aged; Pharyngeal Diseases; Pharynx; Tomography, X-Ray Computed; Warfarin

Chronic expanding hematoma is a rare presentation of a hematoma characterized by a persistent increase in size for more than a month after the initial hemorrhage. We present a 65-year-old man with a chronic expanding hematoma in his ilium who was receiving anticoagulant treatment. The patient had a delayed manifestation of a femoral neuropathy with massive bone destruction. 2-Deoxy-[18F]fluoro-D: -glucose (FDG) positron emission tomography (PET) imaging revealed an increased uptake in the rim of the mass in images acquired 1 h after FDG injection. FDG-PET scans were performed using a dedicated PET scanner (HeadtomeV/SET2400 W, Shimadzu, Kyoto, Japan), and the PET data for the most metabolically active region of interest (ROI) were analyzed. The maximum standardized uptake value (SUVmax) was set to a cut-off point of 3.0 to distinguish between benign and malignant lesions. The SUVmax of the patient's lesion was 3.10, suggesting a malignant lesion. The characteristics of FDG-PET images of chronic expanding hematomas, including the uptake of FDG in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall in mimicking a sarcoma.

Topics: Aged; Anticoagulants; Bone Diseases; Chronic Disease; Fluorodeoxyglucose F18; Hematoma; Humans; Ilium; Male; Positron-Emission Tomography; Radiopharmaceuticals; Warfarin

Topics: Atrial Fibrillation; Chronic Disease; Contraindications; Data Collection; Drug Interactions; Humans; Retrospective Studies; 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

Topics: Aged; Animals; Atrial Fibrillation; Chondroitin Sulfates; Chronic Disease; Contraindications; Drug Combinations; Drug Interactions; Drug Synergism; Glucosamine; Humans; International Normalized Ratio; Manganese Compounds; Self Medication; Sulfates; Warfarin

Chronic atrial fibrillation is a prevalent cardiac disorder. The literature indicates varying proportions of those treated with anticoagulants, and varying intensity of anticoagulation. Electronic patient records are providing us with clinical data concerning management of anticoagulant treatment in real-life practice that is useful for audits. We aimed to assess warfarin treatment for chronic atrial fibrillation in primary health care with regard to prevalence, incidence, the proportion treated and the quality of anticoagulation control.. Five primary health care centres in Stockholm with a registered population of 75146 participated in a one-year retrospective study of electronic patient records up until May 2000. All patients over 18 years of age with an encounter labelled 'Atrial fibrillation' were identified, and all records of patients on warfarin treatment were manually reviewed. Main outcome measures were number of patients with chronic atrial fibrillation, number of patients on wafarin treatment, and time within the therapeutic prothrombin range.. In total, 419 patients had chronic atrial fibrillation, giving a prevalence of 0.60% (age-adjusted 0.62%), the age group 65 years or older accounted for 91.6%, and 50.1% were women. Out of these, 50.4% (211 patients) were established on warfarin treatment for chronic atrial fibrillation (0.28% of the population), and there was a predominance of men (p = 0.02). Fifty-four patients started treatment with warfarin for chronic atrial fibrillation (0.07% of the population). Among 25 randomly selected patients on established treatment, the proportion of time within the therapeutic range was 70.2%. Among 24 randomly selected patients starting treatment, the proportion of time with therapeutic values was 54.2% and 66.9% the first and second months of treatment, respectively.. Chronic atrial fibrillation is common among the elderly in primary health care, and about half of these patients are treated with warfarin. It appears to be under-diagnosed, and may also be under-treated. About two thirds of treatment time is spent within the therapeutic range, and further improvement of the quality of anticoagulation control with warfarin may therefore be hard to achieve.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Female; Humans; Male; Medical Records Systems, Computerized; Middle Aged; Primary Health Care; Quality Assurance, Health Care; Retrospective Studies; Sweden; Warfarin

There is evidence for the activation of the coagulation system and a hypercoagulable state following cardioversion. The aim of the study was to determine whether electrical cardioversion in patients with chronic atrial fibrillation induced a prothrombotic state despite optimal anticoagulation. We studied the effects of electrical cardioversion on plasma levels of fibrinogen, antithrombin III, protein C and D-dimers.. We studied 24 patients with chronic atrial fibrillation who were on optimal anticoagulation and were referred for electrical cardioversion. Samples of venous blood were taken 2 h pre and post cardioversion and 1 month later.. Plasma median concentrations of fibrinogen decreased significantly from 3.8 g/l (interquartile range 3.1-4.2 g/l) before cardioversion to 3.5 g/l (interquartile range 2.9-3.9 g/l) 2 h after cardioversion levels (P=0.004). The fibrinogen levels at 1 month post cardioversion (3.45 g/l, interquartile range 3.1-3.9 g/l) were also significantly lower than baseline (P=0.02). Plasma median levels of antithrombin III fell from 93.5 U/dl (interquartile range 89.3-97.0 U/dl) pre cardioversion to 89.5 U/dl (interquartile range 83.0-93.0 U/dl) 2 h after cardioversion (P=0.001) and returned to normal by 1 month (94.0 U/dl; interquartile range 89.3-98.5 U/dl; P=0.0001). There were no significant changes in plasma median D-dimer or protein C levels at any time.. We have demonstrated a significant fall in the plasma fibrinogen and antithrombin III levels in patients with chronic atrial fibrillation early after electrical cardioversion, indicating thrombin generation. This study suggests that there are haemostatic changes of thrombogenesis induced by cardioversion despite optimal anticoagulation with warfarin.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Atrial Fibrillation; Biomarkers; Blood Coagulation; Chronic Disease; Electric Countershock; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Protein C; Treatment Outcome; United Kingdom; Warfarin

To define the incidence, contemporary utilization patterns, efficacy, and complications of thromboembolic prophylactic treatment in patients with chronic (CAF) and paroxysmal atrial fibrillation (PAF).. Although recent randomized trials with antithrombotic therapy in nonrheumatic atrial fibrillation (AF) patients emphasized the benefits of warfarin in preventing stroke, warfarin treatment is still far from optimal.. A retrospective analysis of the medical records of 506 patients with nonrheumatic PAF or CAF from 23 clinics in the north of Israel, including an interview with the patients' family physician.. (1) The most effective treatment for preventing thromboembolic events (a reduction of 75.9%) was warfarin at an international normalized ratio (INR) intensity of 2-3. (2) After diagnosis, 26.9% of the patients were treated with warfarin. (3) During the follow-up period (not following a thromboembolic event), an additional 26.9% of the patients began treatment with warfarin. (4) Elderly patients (p<0.001), patients with limited activity of daily living (ADL) (p<0.012) or instrumental activity of daily living (IADL) (p<0.001), and patients with PAF (p<0.0001) were less likely to be treated with warfarin. (5) Three new risk factors found for thromboembolic event were limited ADL (p<0.001), limited IADL (p<0.002), and extended duration of AF (p<0.006).. Less than optimal utilization patterns of thromboembolic prophylactic treatment with anticoagulants were found, especially regarding elderly patients, patients with limited ADL and IADL, and patients with PAF, despite the fact that their thromboembolic risk is as high or higher than that of other patients with AF.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Female; Follow-Up Studies; Hemorrhage; Humans; Israel; Male; Middle Aged; Patient Selection; Platelet Aggregation Inhibitors; Retrospective Studies; Thromboembolism; Warfarin

Although many clinical trials have demonstrated that anticoagulant therapy substantially reduces the risk of ischemic stroke in patients with atrial fibrillation (AF), some physicians are reluctant to use anticoagulants. We investigated attitudes of physicians in Japan toward anticoagulant therapy in chronic AF patients.. We conducted a survey at the annual meeting of the Japanese Society of General Medicine. We presented subject physicians with 8 vignettes of chronic AF patients and requested that they indicate their most favored choice of therapy from among 6 strategies including warfarin and aspirin.. We distributed 209 questionnaires and received 139 replies (67% response rate). For all 8 vignettes presented, only 26% of the respondents preferred to use anticoagulant therapy in AF patients. Longer clinical experiences and responsibility at a teaching hospital were associated with negative attitude toward anticoagulant therapy, while experience of preventive therapy in patients with thromboembolism due to AF and strong influence of clinical trials of anticoagulant prophylaxis on their practice were associated with positive attitude toward the therapy. Among patient characteristics in the vignettes, a risk of thromboembolism was positively associated with preference for anticoagulant therapy, but an advanced age and a risk of bleeding complications were negatively associated with the preference for the therapy.. The physicians in Japan in this survey, especially those with longer clinical experiences or responsibility at a teaching hospital, have a negative attitude toward anticoagulant therapy in chronic AF patients. An advanced age and a risk of bleeding complications of patients are deterrent factors to the use of anticoagulant therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Attitude of Health Personnel; Chronic Disease; Drug Utilization; Electrocardiography; Female; Health Care Surveys; Humans; Japan; Male; Middle Aged; Practice Patterns, Physicians'; Probability; Severity of Illness Index; Stroke; Surveys and Questionnaires; Warfarin

The number of patients receiving anticoagulant treatment is increasing. Chronic atrial fibrillation is the most common treatment diagnosis. The literature indicates a variable level of treatment control. Estimates of time within the therapeutic range have been recommended as a measurement of quality. Electronic patient records are providing clinical data that are useful for audits concerning anticoagulant treatment in real-life practice.. Our aim was to assess warfarin treatment for chronic atrial fibrillation in primary health care with regard to prevalence, incidence and quality.. A 2 year retrospective study was carried out of electronic patient records up to April 2002 in primary health care in Stockholm, including 12 primary health care centres with a registered population of 203 407. Main outcome measures were the number of new patients on wafarin treatment for chronic atrial fibrillation, and time within the therapeutic prothrombin range in the first 90 days of treatment using a linear interpolation method.. In total, 827 patients were on warfarin treatment for chronic atrial fibrillation, giving a prevalence of 0.41%. Of these, 144 patients (study group) started treatment with warfarin for chronic atrial fibrillation during the study period, giving a yearly incidence of 0.07%. Their mean age was 73.1 years and 61.1% were men. There were 1721 prothrombin monitoring episodes registered in the first 90 days of treatment, on average once a week per patient. The average proportion of time within the therapeutic range was 54.1% (95% confidence interval (CI) 50.1-58.1), and the proportion of therapeutic tests was 50.2% (95% CI 47.8-52.6).. During the first, second and third months of warfarin treatment for chronic atrial fibrillation, patients were outside the therapeutic range time nearly half the time. There was a gender difference favouring men regarding initiation of treatment.

Topics: Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Chronic Disease; Cohort Studies; Community Health Centers; Drug Utilization Review; Female; Humans; Incidence; Linear Models; Male; Medical Records Systems, Computerized; Middle Aged; Prevalence; Primary Health Care; Quality of Health Care; Sweden; Time Factors; Warfarin

To correlate the presence of non valvar atrial fibrillation (NVAF) and cardioembolic stroke in patients previously assisted by cardiologists and without restrictions to the use of warfarin, with the level of acceptance of the recommendations published about chronic AF among these professionals.. All strokes accepted in two hospitals of Joinville were prospectively recorded. The patients with AF were questioned about their previous knowledge about arrythmia, the frequency they had seen their cardiologists and the use of warfarin. Later, 11 cardiologists answered to questions about AF, anticoagulation and stroke.. Among 167 patients with stroke, 22 were found with ischemic stroke and previous AF. Fifteen of them had previously seen by a cardiologist. Nine patients died, seven were discharged with warfarin and six did not have prescription of anticoagulant. The cardiologists answers presented that 91% of them knew these recommendations, although only 54 % found them applicable to public service's patients.. Considering that anticoagulation in NVAF reduces the relative stroke risk in 68% per year, we can conclude that 11 in 22 patients could have avoided the event. Thus, considering the stroke incidence in 1997 and current population in Joinville, we may speculate that currently 4% of all stokes per year in Joinville are potentially avoidable.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brazil; Chronic Disease; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Prospective Studies; Risk Factors; Sex Distribution; Socioeconomic Factors; Stroke; Warfarin

A SPORTIF-III substudy.. Warfarin has been considered to provide more stable anticoagulant effect than acenocoumarol due to its longer half-life.. The aim of this SPORTIF-III substudy was to compare acenocoumarol (A) with warfarin (W) in the same group of 74 patients, with chronic atrial fibrillation who started with W and then changed to A.. We compared prospectively a 3 months period on W with a 3 months period on A.. The mean number of INR measurements per patient was 5.7 +/- 1.2 and 5.4 +/- 1.6 resp (NS). The mean percentage of INR-s in the therapeutic range of 2-3 was 49 +/- 22.6% for W and 56 +/- 26.8% for A (p < 0.05), the percentage of subtherapeutic values were not different, the supratherapeutic values however occurred more frequently on W (28 +/- 20%) than on A (19 +/- 19%), p < 0,001. There was a good correlation between A and W doses (r = 0.65, p < 0.001), the mean W dose was 5.03 +/- 1.99 mg, the mean A dose was 2.5 +/- 1.3 mg, the W/A dose ratio was computed to be 2.18 +/- 0.78.. 1. anticoagulation effect stability was superior for A compared to W; 2. W/A dose ratio was 2.18.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Treatment Outcome; Warfarin

Topics: Anticoagulants; Catheterization, Peripheral; Chronic Disease; Clinical Trials as Topic; Fibrinolytic Agents; Heparin; Humans; Infusions, Intravenous; Recurrence; Stents; Streptokinase; Thrombolytic Therapy; Thrombophlebitis; Ultrasonography; Venous Insufficiency; Venous Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Drug Utilization; Humans; Regression Analysis; Risk Factors; Warfarin

Topics: Aspirin; Atrial Fibrillation; Chronic Disease; Humans; Warfarin

To measure the use, appropriateness, and safety of antithrombotic therapy in Hong Kong Chinese patients with atrial fibrillation.. Retrospective review.. Regional hospital, Hong Kong.. Medical records of all patients with atrial fibrillation admitted to acute internal medicine wards in April 2000 and between July and October 2001 were reviewed for details of antithrombotics given, results of international normalised ratio monitoring for patients receiving warfarin, side-effects, and additional risk factors for complications of atrial fibrillation. Statistical analysis was undertaken to assess factors predictive of antithrombotic use.. A total of 207 patients with chronic atrial fibrillation were included in the study. Of these, 44.0% of patients with non-valvular atrial fibrillation without contra-indications for warfarin use were receiving warfarin, 34.1% were receiving aspirin, and 22.0% were receiving no antithrombotic therapy. The majority of patients (69.1%) were treated appropriately according to the American College of Chest Physicians guidelines. The major side-effect rates for warfarin and aspirin were 2.14% and 1.72% per patient-year, respectively, which were comparable with western studies of usual clinical practice. The ischaemic stroke rate for patients taking warfarin or aspirin were 1.40% and 6.02% per patient-year, respectively. The median international normalised ratio was 1.96. The median frequency of international normalised ratio measurement was 45.58 days.. This study found that antithrombotic use in a Hong Kong regional hospital for patients with atrial fibrillation was similar to that reported from western institutions. Complication and stroke rates were also comparable to the western data relating to usual clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Chronic Disease; Contraindications; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Warfarin

We present a patient receiving chronic anticoagulant treatment with recurrent and intractable gastrointestinal bleeding due to diffuse angiodysplasia. Following failure of previous medical and surgical treatment, and in light of the patient's need for chronic anticoagulation due to mechanical heart valve, she was treated with somatostatin analogue, octreotide s.c. 100 microg on alternate days for 28 months. Treatment significantly decreased the occurrence of bleeding episodes, the need for hospitalization and blood transfusion requirements despite continued anticoagulant therapy. Octreotide treatment should be considered in patients with refractory gastrointestinal bleeding due to angiodysplasia in particular in those who need anticoagulant treatment.

Topics: Aged; Angiodysplasia; Anticoagulants; Chronic Disease; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Hemostatics; Humans; Octreotide; Warfarin

We report herein a patient in whom a very large and old thrombus in the left atrium was detected by transesophageal echocardiography. The patient started warfarin and aspirin. After 2 years of therapy, transesophageal echocardiography showed the complete resolution of thrombus in the absence of clinical evidence of embolism. This case indicates that large and presumably organized thrombi may be dissolved by an anticoagulant therapy, although the lytic activity of warfarin has never been demonstrated. Transesophageal echocardiography helps in the identification and follow-up of such conditions and contributes to understanding of warfarin action in left atrial thrombosis.

Topics: Anticoagulants; Aspirin; Chronic Disease; Coronary Thrombosis; Drug Therapy, Combination; Echocardiography, Transesophageal; Heart Atria; Humans; Male; Middle Aged; Warfarin

Allocation of additional resources for establishing or expanding anticoagulation clinic (AC) services is a significant concern for healthcare decision-makers when the payer is also the provider of the healthcare system. The majority of anticoagulated patients in Hong Kong are managed by routine medical care (RMC) instead of ACs, possibly due to the lack of local cost-effectiveness analysis of the AC setting. The aim was to compare the clinical and economic outcomes of anticoagulated patients who were managed by AC or RMC from the perspective of a public health organization in Hong Kong. A Markov model was designed to simulate, over 10 years, the economic and clinical outcomes of patients receiving chronic warfarin therapy managed by AC or RMC. The transition probabilities were derived from literature. Resource utilization was retrieved from patients managed by AC and RMC in Hong Kong. Sensitivity analysis was conducted to examine the robustness of the model. The total number of events per 100 patient-years and the direct medical cost per patient-year in the AC and RMC groups were 9.5 and USD 840, and, 19.3 and USD 1,179, respectively. The results of the model were sensitive to the variation of the probability of major bleeding in the AC group. In conclusion, the coordinated care provided by an anticoagulation clinic appears to be more cost-effective than routine medical care in the management of warfarin therapy from the perspective of public health organization in Hong Kong.

Topics: Algorithms; Ambulatory Care Facilities; Chronic Disease; Cost-Benefit Analysis; Disease Management; Health Care Costs; Hemorrhage; Humans; Markov Chains; Public Health Administration; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is associated with hemostatic abnormalities and increased risk of thrombotic cardiovascular events even during oral anticoagulant therapy (OAT). The aim of our study was to evaluate the predictive value of hemostatic markers for the risk of major cardiovascular events during OAT. The study group comprised 113 patients with chronic AF (70.2 +/- 5.4 years old, 60% men), referred for OAT. Established clinical risk factors and levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen and activity, before and during OAT (after 3.9 +/- 0.7 months; INR 2.57 +/- 0.57) were determined. In all patients OAT significantly suppressed levels of F1+2 by 67%,TAT by 30% and D-dimer by 48% (all p <0.001). During an average follow-up of 44 months 22/111 (20%) patients suffered a combined cardiovascular event (stroke, myocardial infarction, peripheral vascular occlusion or vascular death). Patients with cardiovascular events were significantly older, had more frequent heart failure/systolic dysfunction and had significantly increased levels of D-dimer at entry (63 vs 39 ng/mL, p = 0.005) and during OAT (33 vs 18 ng/mL, p = 0.002), and of t-PA antigen at entry (14.3 vs 10.9 ng/mL, p = 0.02) and during OAT (15.0 vs 11.2 ng/mL, p = 0.05) (all values are medians). In multivariate Cox proportional hazard models, heart failure/systolic dysfunction (hazard ratio 2.91; 95% CI 1.17-7.26; p = 0.02), high levels of D-dimer on OAT (top vs. lower two quartiles) (hazard ratio 4.78, 95% CI 1.39-16.41; p = 0.01) and t-PA antigen levels (continuous variable) (hazard ratio 1.09; 95% CI 1.01-1.17; p = 0.02) were significantly associated with combined cardiovascular events. In conclusion, high levels of D-dimer and t-PA antigen during OAT are significant predictors of combined cardiovascular events in AF patients and, on this basis, could be useful additional markers of cardiovascular risk in such patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Hemostasis; Humans; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Tissue Plasminogen Activator; Warfarin

Acute renal vein thrombosis in a renal allograft is uncommon and usually occurs in the post-transplant period. Chronic renal vein thrombosis can occur insidiously many years after transplant without significant deterioration in renal allograft function or symptoms.

Topics: Adult; Anticoagulants; Chronic Disease; Collateral Circulation; Femoral Vein; Humans; Iliac Vein; Kidney Transplantation; Male; Phlebography; Renal Circulation; Renal Veins; Tomography, X-Ray Computed; Transplantation, Homologous; Treatment Outcome; Venous Thrombosis; Warfarin

A 65 year old man, anticoagulated for cardiac problems, developed hemiparesis while training for race walking. A computed tomography scan showed a chronic subdural haematoma. This is the first report of a chronic subdural haematoma possibly caused by the jarring action of race walking.

Topics: Aged; Anticoagulants; Chronic Disease; Hematoma, Subdural; Humans; Male; Radiography; Walking; Warfarin

We describe a case of thoracic aortic aneurysm complicated by chronic disseminated intravascular coagulation (DIC). Initially the DIC was controlled successfully by administration of gabexate mesilate and dalteparin. However, because these drugs were given intravenously, the patient could not be discharged. Subsequently, the DIC was treated successfully by changing to orally administered camostat mesilate, warfarin and aspirin, which allowed the patient to leave hospital.

Topics: Administration, Oral; Aged; Anticoagulants; Aortic Aneurysm, Thoracic; Aspirin; Chronic Disease; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Esters; Gabexate; Guanidines; Humans; Male; Warfarin

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Chronic Disease; Drug Utilization; Female; Humans; Male; Middle Aged; Risk; Stroke; Warfarin

The benefits of antithrombotic therapy in chronic atrial fibrillation (AF) have been established in clinical trials, but there is a paucity of data on outcomes in practice.. The objective was to establish a large ongoing database of patients with non-valvular AF, to enable the accurate determination of clinical outcomes.. A retrospective review of the medical records for consecutive patients who had AF documented on electrocardiogram at the major teaching hospital in Tasmania between 1 January 1997 and 30 June 1999 was performed. An extensive range of demographic and clinical variables was recorded for all patients with chronic or paroxysmal non-valvular AF.. The 505 patients (60% males) included in the database had a median age of 76 years. According to risk stratification criteria, 79% of the patients with previously diagnosed chronic or paroxysmal AF had a high risk of developing stroke at the time of admission to hospital care. However, only one-third (34%) of these patients were receiving warfarin (or warfarin plus aspirin), with almost one-quarter (24%) receiving no antithrombotic agent. The annual incidence of ischaemic strokes was 3.4% (1.5-6.4%; 95% CI) when taking warfarin, compared to 7.0% (5.2-9.4%) for patients not taking warfarin and 7.8% (5.4-11.1%) for patients taking aspirin. The annual incidence of bleeding complications in patients taking warfarin was 14.2% (10.0-19.5%) overall and 3.4% (1.5-6.4%) for major bleeds. In patients not taking warfarin, the overall annual incidence of bleeds was 8.4% (6.3-10.9%) and 3.9% (2.5-5.7%) for major bleeds.. Warfarin is underused in patients with AF. In clinical practice, warfarin confers a similar stroke risk reduction to that observed in trials, with an increase in incidence of only minor bleeding complications. Aspirin did not appear to reduce the risk of stroke.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Databases, Factual; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Thromboembolism; Treatment Outcome; Warfarin

There is a perception that patients who develop a chronic subdural haematoma (CSDH), whilst taking warfarin, do less well than those not taking warfarin. This study looks at such patients to determine the truth of this perception. A retrospective analysis of two time periods (1990-1992 and 1995-1997) looking at all patients with CSDH admitted to this neurosurgical unit for treatment, to determine the incidence and to look more closely at those on warfarin. The influence of warfarin on the incidence, severity and outcome has been studied. Between 1990 and 1992, 11.8% of those patients with CSDH were taking warfarin, whilst in 1995-1997 20% were on warfarin. The overall number of referrals of CSDH increased from 34 to 150 patients during these time periods. There were no differences in age, sex or other medical disorders between the two groups. No adverse events occurred when the warfarin was stopped temporarily for treatment of the CSDH. There was no increase in recurrence rate in those on warfarin, compared with those not on warfarin. This study, whilst demonstrating an increase in the number of referrals of CSDH and patients with CSDH taking warfarin, has not demonstrated an adverse effect of the warfarin on the outcome of treatment for CSDH. The authors suggest recommencing warfarin 3 weeks after surgical evacuation of CSDH in anticoagulated patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Female; Glasgow Coma Scale; Glasgow Outcome Scale; Hematoma, Subdural; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Treatment Outcome; Warfarin

To survey physicians' anticoagulation preferences in patients with chronic atrial fibrillation who are undergoing elective surgery.. A survey was performed that asked physicians to provide pre- and postoperative anticoagulation preferences for two clinical scenarios of patients with chronic atrial fibrillation (high stroke risk, low stroke risk) undergoing elective surgery. In addition to the interruption of warfarin therapy, perioperative anticoagulation options were as follows: a) in-hospital full dose intravenous heparin; b) outpatient full dose subcutaneous unfractionated heparin or low molecular weight heparin (LMWH); c) low dose unfractionated heparin or LMWH (postoperative only); d) nothing other than stopping warfarin preoperatively and restarting it postoperatively; or e) another anticoagulant strategy.. In the high stroke risk scenario, the proportions of respondents preferring anticoagulation options a, b, d and e in the preoperative period were 24%, 20%, 54% and 2%, respectively; the proportions preferring options a, b, c, d and e in the postoperative period were 35%, 13%, 15%, 35% and 1%, respectively. In the low stroke risk scenario, the proportions of respondents preferring options a, b, d and e in the preoperative period were 7%, 10%, 80% and 3%, respectively; the proportions preferring options a, b, c, d and e in the postoperative period were 11%, 9%, 10%, 68% and 2%, respectively.. In patients with chronic atrial fibrillation who underwent elective surgery, perioperative anticoagulant management preferences varied widely in patients at high risk for stroke, but were more uniform and less aggressive in patients at low risk for stroke.

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Elective Surgical Procedures; Heparin; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Postoperative Period; Practice Patterns, Physicians'; Preoperative Care; Risk; Stroke; Warfarin

Despite exclusion of left atrial thrombi by transoesophageal echocardiography, cardioversion-related thromboembolism has been reported in atrial fibrillation or flutter. To define a low-risk group for cardioversion without previous anticoagulation, patients were selected for immediate cardioversion if there were no thrombi, no echo spontaneous contrast and the outflow velocity of the left atrial appendage was greater than 0.25 m. s(-1)on transoesophageal echocardiography.. Two hundred and forty-two consecutive patients referred for cardioversion of atrial fibrillation or flutter with a duration of more than 2 days and no anticoagulation therapy were examined with transoesophageal echocardiography. After the transoesophageal echocardiography examination, patients who were eligible for immediate cardioversion were anticoagulated with low molecular weight heparin (dalteparin) subcutaneously, together with warfarin prior to cardioversion. Dalteparin treatment was continued until the patient had reached therapeutic prothrombin values. Based on the transoesophageal echocardiographic findings the patients were divided into two groups: immediate cardioversion, group A, with a mean age of 62+/-13 years (n=162); or conventional warfarin treatment before cardioversion, group B, with a mean age of 67+/-10 years (P<0.05) (n=80). In group A, lone atrial fibrillation or flutter was more common (53%; 95% CI: 45-61) compared to group B (34%; 95% CI: 23-44, P<0.05), while heart disease was more common in group B (45%; 95% CI: 34-56) compared to group A (31%; 95% CI: 24-39, P<0.05). Echocardiography revealed thrombi in 5% (95% CI: 2.6-8) of the patients, left atrial size was larger, fractional shortening lower, and a higher proportion had impaired left ventricular function in group B. No thromboembolic event occurred at or after cardioversion in any of the patients; however, before planned cardioversion one transitory ischaemic attack, one lethal stroke and one cardiac death occurred in three of the patients with thrombi despite warfarin therapy. One-month follow-up maintenance of sinus rhythm was 75% in group A compared to 45% in group B (P<0.01).. After using our transoesophageal echocardiographic exclusion criteria (no thrombi, no spontaneous echo contrast and left atrial appendage outflow velocity > or = 25 m. s(-1)) cardioversion can safely be performed in 2/3 of patients with atrial fibrillation or flutter without previous anticoagulation therapy. These patients maintained sinus rhythm significantly better after 1 month compared to patients with prolonged warfarin therapy before cardioversion.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Chronic Disease; Echocardiography, Transesophageal; Electric Countershock; Female; Humans; Logistic Models; Male; Middle Aged; Patient Selection; Warfarin

The value of warfarin in preventing stroke in patients with chronic atrial fibrillation is well established. However, the prevalence of such treatment generally lags behind actual requirements. The aim of this study was to evaluate doctor- and/or patient-related demographic, clinical, and echocardiographic factors that influence decision for warfarin treatment.. Between 1990 and 1998, 1027 patients were discharged with chronic or persistent atrial fibrillation. This population was composed of (1) patients with cardiac prosthetic valves (n=48), (2) those with increased bleeding risks (n=152), (3) physically or mentally handicapped patients (n=317), and (4) the remaining 510 patients, the main study group who were subjected to thorough statistical analysis for determining factors influencing warfarin use.. The respective rates of warfarin use on discharge in the 4 groups were 93.7%, 30.9%, 17.03%, and 59.4% (P=0.001); of the latter, an additional 28.7% were discharged on aspirin. In the main study group, warfarin treatment rates increased with each consecutive triennial period (29.7%, 53.6%, and 77.1%, respectively; P=0.001). Age >80 years, poor command of Hebrew, and being hospitalized in a given medical department emerged as independent variables negatively influencing warfarin use: P=0.0001, OR 0.30 (95% CI 0.17 to 0.55); P=0.02, OR 0.59 (95% CI 0.36 to 0.94); and P=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In contrast, past history of stroke and availability of echocardiographic information, regardless of the findings, each increased warfarin use (P=0.03, OR 1.95 [95% CI 1.04 to 3.68], and P=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively).. Old age, language difficulties, insufficient doctor alertness to warfarin benefit, and patient disability produced reluctance to treat. Warfarin use still lags behind requirements.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Communication Barriers; Comorbidity; Drug Prescriptions; Drug Utilization; Echocardiography; Female; Heart Diseases; Hospital Departments; Hospitalization; Humans; Israel; Lung Diseases, Obstructive; Male; Middle Aged; Physician-Patient Relations; Physicians; Practice Patterns, Physicians'; Recurrence; Refusal to Treat; Retrospective Studies; Risk Factors; Stroke; Thyrotoxicosis; Warfarin

Topics: Aged; Algorithms; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Echocardiography, Transesophageal; Female; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk; Stroke; 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

A multicenter, retrospective study was undertaken to survey the prevalence of thromboembolism complicated with atrial fibrillation and the efficacy of treatment in both elderly and younger patients. The primary prevention group consisted of 1,810 patients without prior cerebral thromboembolism, and was divided into the elderly patient group (> or = 65 years old, 588 patients) and younger patient group (< 65 years old, 1,222 patients). The elderly group had higher prevalences of chronic atrial fibrillation (65.3% vs 56.4%, p < 0.001) and ischemic heart disease and hypertension (16.8% vs 9.3% and 34.2% vs 24.4%, respectively, p < 0.001) and lower prevalence of treatment with warfarin (9.2% vs 20.1%, p < 0.001). Elderly patients with mitral valve disease and hypertension had lower prevalence of treatment with warfarin as compared with younger patients (p < 0.001). This was also true for the secondary prevention group of 147 patients with prior history of cerebral infarction (p < 0.001). During the mean follow-up period of 4.6 years, patients with underlying cardiac diseases had a higher risk of thromboembolism compared with those without cardiac diseases for both the elderly (12.1% vs 6.1%, p < 0.05) and younger (7.5% vs 3.6%, p < 0.02) groups. Treatment with antiplatelets or warfarin could reduce the risk of thromboembolism in the elderly group (p < 0.1) and the younger group (p < 0.001). The risk of major hemorrhagic complication, i.e., gastrointestinal tract or intracranial hemorrhage, was quite low in patients receiving antithrombotic drugs. The present study indicates that the attitude toward the use of warfarin for prevention of thromboembolism is conservative and the risk of thromboembolism is higher in elderly patients with atrial fibrillation in Japan. Our attitude to the use of antithrombotic drugs in elderly patients with atrial fibrillation needs to be modified.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Female; Hemorrhage; Humans; Hypertension; Japan; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prevalence; Retrospective Studies; Thromboembolism; Warfarin

To investigate the incidence of new thromboembolic (TE) stroke in older persons with chronic atrial fibrillation treated with oral warfarin versus aspirin.. In an observational study of 312 older persons with chronic atrial fibrillation, long-term aspirin 325 mg daily was administered to 187 persons, and oral warfarin, in a dose adjusted to maintain the international normalized ratio (INR) between 2.0 and 3.0, was administered to 115 persons. The incidence of new TE stroke was analyzed in persons treated with warfarin versus aspirin at 36 +/- 17 months (1 to 99 months) follow-up.. A large, long-term healthcare facility.. The patients included 208 women and 104 men, mean age 84 +/- 7 years (range 62 to 101 years).. Four of 125 persons (3%) on warfarin stopped taking warfarin compared with four of 187 persons (2%) on aspirin who stopped taking aspirin because of adverse effects (P not significant). In persons with prior stroke, the incidence of new TE stroke was 40% (27 of 67) in persons treated with warfarin versus 81% (56 of 69) in persons treated with aspirin (P < .001). In persons with no prior stroke, the incidence of new TE stroke was 22% (13 of 58) in persons treated with warfarin versus 56% (66 of 118) in persons treated with aspirin (P < .001). The incidence of new TE stroke in all subjects was 32% (40 of 125) in persons treated with warfarin versus 65% (122 of 187) in persons treated with aspirin (P < .001). Cox regression analysis showed that persons taking warfarin had a 76% less chance of developing a new TE stroke than those taking aspirin after controlling the confounding effects of other risk factors.. In an observational study of older persons with chronic atrial fibrillation, persons treated with oral warfarin to maintain an INR between 2.0 and 3.0 had a significantly lower incidence of new TE stroke than persons treated with oral aspirin 325 mg daily.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Female; Follow-Up Studies; Humans; Incidence; International Normalized Ratio; Intracranial Embolism and Thrombosis; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Warfarin

Topics: Anticoagulants; Chronic Disease; Drug Administration Schedule; Humans; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis; 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 assess the incidence of arterial embolic events in patients with high rate, drug resistant, severely symptomatic paroxysmal and chronic atrial fibrillation who have undergone atrioventricular (AV) node ablation and permanent pacing.. Multicentre retrospective cohort study. PATIENTS AND MANAGEMENT: From May 1987 to January 1997, AV node ablation was performed in 585 severely symptomatic patients (mean (SD) age 66 (11) years) with high rate, drug resistant paroxysmal atrial fibrillation (308) or chronic atrial fibrillation (277). Lone atrial fibrillation was present in 133 patients, while the remaining 452 suffered from dilated, ischaemic, or valvar heart disease. Patients underwent VVIR (454) or DDDR (131) pacemaker implantation, after AV node ablation. Antiplatelet agents were given to 202 patients, warfarin to 187 patients.. During a follow up of 33.6 (24.2) months, thromboembolic events were observed in 17 patients (3%); the actuarial occurrence rates of thromboembolism were 1.1%, 3%, 4.2%, and 7.4% after one, three, five, and seven years, respectively. Among five variables, univariate analysis showed that only the presence of chronic atrial fibrillation at the time of ablation (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.02 to 3. 20, p = 0.04) and the need for warfarin treatment (RR = 1.6, 95% CI 1.00 to 2.71, p = 0.048) were associated with a significantly higher risk of occurrence of thromboembolic events. On multivariate analysis the only predictor of embolic events during the follow up was the presence of chronic atrial fibrillation.. Data from this large cohort of patients indicate a fairly low incidence (1.04% per year) of thromboembolic events after AV node ablation and pacing for drug refractory, high rate atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Atrioventricular Node; Cardiac Pacing, Artificial; Catheter Ablation; Chronic Disease; Follow-Up Studies; Humans; Incidence; Platelet Aggregation Inhibitors; Postoperative Complications; Proportional Hazards Models; Retrospective Studies; Risk; Thromboembolism; Warfarin

This study examined the factors associated with the development of chronic (or permanent) atrial fibrillation (AF) in patients who had undergone atrioventricular (AV) node ablation with permanent pacing because of paroxysmal AF.. A retrospective review of case notes of all 65 consecutive patients identified as having had paroxysmal atrial arrhythmias, AV node ablation and permanent pacemaker implantation was performed. Atrial rhythm was established from all pacing records and from the surface ECG. Treatment with anti-arrhythmic drugs and with warfarin was recorded. A multivariate analysis was undertaken, using atrial rhythm on final ECG and chronic AF as outcome measures.. During a mean follow-up of 30 months, 42% of patients with paroxysmal AF had developed chronic AF. Multivariate analysis showed that increasing age, history of electrical cardioversion and VVI pacing all contributed to the development of chronic AF. 25/62 patients were taking warfarin, and four had had strokes (2.5%/year).. The majority of patients with paroxysmal atrial arrhythmias treated with AV node ablation and pacing develop chronic AF eventually. Stroke remains a risk, particularly in those who develop chronic AF.

Topics: Anticoagulants; Atrial Fibrillation; Atrioventricular Node; Catheter Ablation; Chronic Disease; Combined Modality Therapy; Electric Countershock; Electrocardiography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Pacemaker, Artificial; Retrospective Studies; Risk Factors; Stroke; 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

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

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: Adolescent; Adult; Asthma; Child; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Interactions; Humans; Hydroxyurea; Intestinal Absorption; Leukotrienes; Lipoxygenase Inhibitors; Propranolol; Theophylline; Warfarin

Topics: Abnormalities, Drug-Induced; Acute Disease; Aged; Aged, 80 and over; Aging; Anticoagulants; Chronic Disease; Drug Hypersensitivity; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Forecasting; Gene Expression; Genetic Predisposition to Disease; Humans; Malignant Hyperthermia; Pharmacogenetics; Preventive Dentistry; Preventive Medicine; Risk; Treatment Outcome; Warfarin

Several weeks of prophylactic anticoagulation are routinely prescribed before and after electrical cardioversion of atrial fibrillation. Recent studies have supported the use of transesophageal echocardiography to guide early cardioversion: patients in whom no thrombus is observed are treated with heparin followed by one month of warfarin therapy after the procedure. This kind of treatment requires hospital admission during heparin infusion, because of the need for monitoring partial thromboplastin time.. To evaluate if a short at-home treatment (three days) with warfarin is sufficient to reach a good level of anticoagulation, in order to permit safe electrical cardioversion in day-hospital for patients who show no thrombi on transesophageal echocardiography.. One hundred twenty-four patients with atrial fibrillation, who were candidates for cardioversion, were treated with warfarin: 10 mg the first and second day, 5 mg the third day in group A patients (n = 79); 15 mg the first day, 10 mg the second and third day in group B patients (n = 45). On the fourth day, INR value was measured and if it was < 2, warfarin therapy was prolonged until patients reached a good level of anticoagulation. Transesophageal echocardiography was performed when the INR was > or = 2, and patients were cardioverted with DC shock if there were no thrombi. The patients were discharged on the same day of the procedure, and warfarin therapy was continued for 4 weeks there-after. If a thrombus was detected, patients repeated transesophageal echocardiography after 6 weeks of warfarin therapy, and were cardioverted if the thrombus disappeared. Otherwise, cardioversion was deferred and they received prolonged warfarin treatment. If there was poor visualization of the left atrial appendage, patients received conventional warfarin therapy for 3 weeks before and 4 weeks after electrical cardioversion.. Mean INR value after three days of warfarin treatment was 2.41 in group A patients and 3.02 in group B patients. Twenty-one patients from group A and 3 patients from group B required anticoagulant therapy for a mean of 3.3 and 5.1 days, respectively, before reaching a good level of anticoagulation (INR value > or = 2). Eight patients reverted spontaneously to sinus rhythm before transesophageal echocardiography. Eighteen thrombi (15.5%) were identified on the transesophageal echocardiography, all of which were in the left atrial appendage. In 11 cases, thrombus disappeared after 6 weeks of warfarin therapy. In 7 patients (6%), the atrial appendage was not sufficiently visualized. Electrical cardioversion was performed on 109 patients and was successful in 88 (80.7%). None of them experienced a clinical thromboembolic event.. In the majority of patients in atrial fibrillation, a short at-home warfarin treatment is sufficient to reach a good level of anticoagulation in order to permit safe electrical cardioversion in a day-hospital situation. Larger initial doses can achieve even better results. This treatment algorithm minimizes the anticoagulation period, hospital stay, overall duration of atrial fibrillation and the time required for the mechanical function of the left atrium to return.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Clinical Protocols; Echocardiography; Electric Countershock; Female; Humans; Male; Middle Aged; Thrombolytic Therapy; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Drug Therapy, Combination; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Thromboembolism; Warfarin

We sought evidence for thromboembolic sequelae after the transient withdrawal of chronic anti-coagulation because of acute GI bleeding.. Our Gastrointestinal Bleeding Team endoscopic database was reviewed over a 5-yr period to identify patients who underwent a transient withdrawal from chronic anticoagulation as a result of acute GI bleeding. Long term follow-up records were available for all study patients and were carefully scrutinized for any symptomatic thromboembolic events.. Twenty-seven patients were included in the study, of which 17 (63%) were on chronic anticoagulation for prosthetic heart valves. Chronic anticoagulation was withheld for a median period of 3 days (range = 2-7 days) for patients with prosthetic heart valves and 7 days (range = 2-15 days) for patients on chronic anticoagulation for other indications. Over a median follow-up period of 8 months (range = 1-54 months), one patient developed documented lower extremity thromboembolism.. We conclude that symptomatic thromboembolism can occur after the transient withdrawal of chronic anticoagulation for acute GI bleeding but that it does not occur frequently.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Middle Aged; Risk Factors; Substance Withdrawal Syndrome; Thromboembolism; Time Factors; Warfarin

To determine whether low-dose aspirin or warfarin induces fecal occult blood loss.. A prospective, cross-over study, of 100 participants over 40 years of age in 1 of 3 groups, taking: (1) no aspirin or warfarin, (2) daily aspirin (either 81 or 325 mg), or (3) warfarin, but no aspirin. Stool samples were collected and analyzed for the presence of occult blood using HemoQuant and Hemoccult II. After collection of baseline samples, patients initially taking no aspirin (group 1) were asked to take regular aspirin (325 mg daily) for 2 months. Patients initially taking aspirin 81 mg daily (group 2) were switched to 325 mg daily for 2 months, and vice versa.. Patients taking no aspirin had mean fecal blood of 0.68 +/- 0.05 mg hemoglobin/g stool, which increased to 1.41 +/- 0.36 mg/g after taking 325 mg of aspirin daily (P = 0.02). In contrast, patients in group 2, taking 81 mg and 325 mg of aspirin, had mean fecal blood of 0.82 +/- 0.08 mg/g (P = 0.57) and 1.04 +/- 0.23 mg/g (P = 0.13), respectively (comparisons with patients taking no aspirin). The mean blood loss in patients taking warfarin was 0.51 +/- 0.04 mg/g (P = 0.55), and fecal blood was not related to the degree of anticoagulation. There was no increase over normal in the rate of Hemoccult II-positive stool tests with aspirin or warfarin therapy.. Aspirin, but not warfarin, caused a small but clinically insignificant increase in occult fecal blood. The small blood loss in patients taking aspirin or warfarin is unlikely to interfere with fecal occult blood test. Therefore, positive fecal occult blood tests, in patients taking either low-dose aspirin or warfarin, should be managed in the same fashion as patients not taking these medications.

Topics: Analysis of Variance; Anticoagulants; Aspirin; Cardiovascular Diseases; Chronic Disease; Cross-Over Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Occult Blood; Platelet Aggregation Inhibitors; Prospective Studies; Specimen Handling; Warfarin

Topics: Anti-Asthmatic Agents; Asthma; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Sulfonamides; Tosyl Compounds; Warfarin

Four patients with prosthetic heart valves suffered intracranial hemorrhage (cerebral hemorrhage in one patient, cerebellar hemorrhage in one, and chronic subdural hematoma in two) during long-term oral anticoagulant drug therapy (warfarin). In all patients, warfarin was discontinued and its effect neutralized by vitamin K, then surgery was performed after the thrombotest value exceeded 50%. No uncontrollable bleeding occurred at surgery. Warfarin was discontinued until 3-7 days postoperatively. Intravenous heparin administration was used to prevent embolic complications and the dose was modified based on the activated clotting time measured at the bedside. One patient, who could not receive heparin administration because of massive bleeding, developed myocardial infarction due to coronary artery thromboembolism 2 days after operation and died 4 days later. The other patients received heparin administration and were alive and well at the most recent follow-up examinations. Heparin administration monitored by activated clotting time is a useful method to prevent embolic and bleeding complications in the surgical treatment of intracranial hemorrhage in patients with prosthetic heart valves receiving long-term anticoagulant therapy.

Topics: Cerebral Hemorrhage; Child; Chronic Disease; Heart Valve Prosthesis; Hematoma, Subdural; Humans; Male; Middle Aged; Time Factors; 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

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; Chronic Disease; Humans; Thromboembolism; Warfarin

Coagulation factors that interfere with the one-stage prothrombin time (PT) were investigated. PT responded with identical activities (adequately) against coagulation factors VII or X, only half as expected against factor IX, less than expected and nonlinearly against factor II. In multiple coagulation factor deficiencies PT did not differ from factor VII, which was the most reduced coagulation factor in warfarin therapy or liver disease. PT may also be influenced by factor VII at high activities.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Chronic Disease; Humans; Liver Diseases; Prothrombin Time; Warfarin

A case of rheumatic heart disease, mitral stenosis, large left atrium, and chronic atrial fibrillation is reported and discussed. This patient was shown, by means of two-dimensional echocardiography, to have a massive left atrial thrombus, and after the initiation of anticoagulation with warfarin, complete resolution of the clot was seen in less than two months. The use of two-dimensional echocardiography was valuable in the follow-up of this patient, and it is suggested that further prospective studies are necessary for better understanding the natural history of left atrial thrombus.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Echocardiography; Female; Heart Atria; Heart Diseases; Humans; Mitral Valve Stenosis; Remission Induction; Thrombosis; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Female; Humans; Male; Middle Aged; Thromboembolism; Thyrotoxicosis; Warfarin

Chronic hypoxia produces pulmonary hypertension and pulmonary vascular remodeling. Heparin partially prevents the rise in right ventricular pressure and vascular remodeling in chronically hypoxic mice. To determine if this is due to the anticoagulant property of heparin or another property, we compared the effect of oral warfarin given at an anticoagulating dose (0.5 mg/kg/day) to heparin given by continuous infusion at a dose that does not prolong the partial thromboplastin time (PTT) (20 units/kg/h) on hypoxic pulmonary hypertension and vascular remodeling in the guinea pig. Normoxic control animals either untreated or treated with heparin or Coumadin were all alike in blood gases, pulmonary vascular resistance, right heart weights, and pulmonary histology. Hypoxia (10% 0(2) for 10 days) induced similar and significant increases in mean pulmonary artery (PA) pressure in both the hypoxic control and warfarin groups (19 +/- 1 mm Hg (mean +/- SEM) in both groups versus 11 +/- 0.1 mm Hg in the normoxic control group; p less than 0.05). Total pulmonary vascular resistance (TPR) was also increased from 0.041 +/- 0.002 in the normoxic control group to 0.087 +/- 0.007 and 0.071 +/- 0.003 mm Hg/ml/min/kg in the hypoxic control and warfarin groups, respectively (p less than 0.05). Whereas anticoagulation with warfarin did not protect the guinea pig from developing pulmonary hypertension, heparin markedly reduced PA and TPR (15 +/- 1 mm Hg and 0.052 +/- 0.002 mm Hg/ml/min/kg, respectively; p less than 0.05 versus hypoxic control or warfarin).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Coagulation; Blood Vessels; Chronic Disease; Guinea Pigs; Hemodynamics; Heparin; Hypertension, Pulmonary; Hypoxia; Male; Partial Thromboplastin Time; Prothrombin Time; Pulmonary Circulation; Warfarin

Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals.

Topics: Adult; Aged; Antigens; Blood Coagulation; Chromogenic Compounds; Chronic Disease; Dipeptides; Disseminated Intravascular Coagulation; Factor VII; Factor X; Glycoproteins; Humans; Immunosorbent Techniques; Liver Diseases; Middle Aged; Protein C; Thrombophlebitis; Warfarin

Topics: Adult; Angioedema; Chronic Disease; Humans; Male; Middle Aged; Patient Compliance; Urticaria; Warfarin

Topics: Chronic Disease; Drainage; Follow-Up Studies; Heart Valve Prosthesis; Hematoma, Subdural; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Warfarin

A 56 year old man was seen because of recurrent right shoulder hemarthroses and a superior vena caval syndrome. Intermittent symptoms had occurred for six years and resulted in marked destructive changes in the right shoulder. Arthroscopy added pathological evidence of this unusual mechanism of arthropathy. Patients on anticoagulants deserve close attention to symptoms of occult bleeding.

Topics: Chronic Disease; Heart Valve Prosthesis; Hemarthrosis; Humans; Male; Middle Aged; Osteoarthritis; Radiography; Warfarin

Diagnosis of renal vein thrombosis, a disease of subtle or dramatic onset, depends largely on clinical suspicion confirmed by renal venography. The principles of management are changing as diagnostic advances resolve the "chicken-or-egg" quandary over the causal relationship between renal vein thrombosis and the nephrotic syndrome.

Topics: Acute Disease; Adult; Child; Chronic Disease; Heparin; Humans; Infant; Nephrotic Syndrome; Phlebography; Renal Veins; Thrombosis; Warfarin

Nonresolution of acute pulmonary embolism and resultant chronic persistent pulmonary occlusion is uncommon; documentation of its occurrence in patients receiving anticoagulants is sparse. We report three cases with hemodynamic data and follow-up of up to seven years. All patients had mild to moderate dyspnea on exertion. All patients had normal resting pulmonary artery pressures; two patients demonstrated pulmonary hypertension with exercise. One patient underwent successful thromboendarterectomy but had subsequent reocclusion secondary to in situ thrombosis. With all patients receiving long-term anticoagulant therapy, there was no clinical recurrence of embolization or progression of symptoms. Patients with chronic persistent pulmonary embolism should be identified and should receive long-term follow-up. Therapy aimed at prevention of recurrent embolization is required. Pulmonary thromboendarterectomy is indicated for selected patients.

Topics: Adult; Blood Pressure; Chronic Disease; Endarterectomy; Female; Follow-Up Studies; Heparin; Humans; Injections, Intravenous; Injections, Subcutaneous; Middle Aged; Pregnancy; Pulmonary Artery; Pulmonary Embolism; Time Factors; Vascular Resistance; Warfarin

Retroperitoneal bleeding in hemodialysis patients has been rearely reported. The diagnosis of this entity in the nondialysis patient is difficult, and factors such as chronic anemia and hypotensive episodes during hemodialysis are adding difficulty to the early diagnosis and therapeutic approach. A patient receiving long-term hemodialysis anticoagulation therapy had retroperitoneal bleeding and died without having his condition diagnosed: the retroperitoneal bleeding was masked by other events occurring during hemodialysis.

Topics: Adult; Chronic Disease; Glomerulonephritis; Hematocrit; Hemoperitoneum; Heparin; Humans; Male; Renal Dialysis; Retroperitoneal Space; Warfarin

Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.

Topics: Adult; Aged; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Brain Neoplasms; Breast Neoplasms; Chronic Disease; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Prothrombin Time; Pulmonary Embolism; Solitary Pulmonary Nodule; Thrombophlebitis; Warfarin

Necrotizing skin lesions developed in a man with chronic ulcerative colitis. No evidence of intrinsic disease of medium or small-sized vessels was found. A circulating cryofibrinogen was thought to be responsible for in situ thrombosis leading to skin infarctions. Sodium warfarin in a daily dose of 2.5 to 5 mg appears to have thwarted progression of developing lesions and the occurrence of new ones.

Topics: Blood Protein Disorders; Chronic Disease; Cold Temperature; Colitis, Ulcerative; Fibrinogen; Humans; Male; Middle Aged; Necrosis; Skin Diseases; Warfarin

Topics: Acute Disease; Adolescent; Adult; Aged; Aneurysm; Child; Chronic Disease; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrinolysis; Hemangioma; Heparin; Humans; Iliac Artery; Infusions, Parenteral; Lung Neoplasms; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Pregnancy; Sepsis; Streptococcal Infections; Syndrome; Thrombophlebitis; Thumb; Warfarin

Topics: Acute Disease; Adolescent; Adult; Aortography; Chronic Disease; Colitis, Ulcerative; Female; Heparin; Humans; Klinefelter Syndrome; Male; Middle Aged; Nephrotic Syndrome; Phlebography; Renal Veins; Thromboembolism; Thrombophlebitis; Thrombosis; Urography; Warfarin

Topics: Chronic Disease; Humans; Leukemia; Lymphoma; Warfarin

Topics: Acute Disease; Adult; Anticoagulants; Arrhythmias, Cardiac; Chronic Disease; Coronary Disease; Dicumarol; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Prothrombin Time; Thrombelastography; Thrombosis; Warfarin

Topics: Chronic Disease; Heparin; Humans; Leg; Pelvis; Phlebography; Pulmonary Embolism; Thrombophlebitis; Warfarin

Topics: Beta-Globulins; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Cryoglobulins; Dipyridamole; Female; Fibrinogen; Heparin; Humans; Immunodiffusion; Immunoelectrophoresis; Middle Aged; Ovarian Neoplasms; Ultracentrifugation; Warfarin