warfarin and Heart-Failure

Several studies have investigated the efficacy and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and heart failure (HF). Herein, this meta-analysis was aimed to compare the effect of NOACs with warfarin in this population. We systematically searched the PubMed database until December 2019 for studies that compared the effect of NOACs with warfarin in patients with AF and HF. Risk ratios (RRs) and 95% confidence intervals (CIs) were abstracted and then pooled using a random-effects model. A total of nine studies were included in this meta-analysis. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism (RR = 0.82 (95% CI, 0.73-0.92)), all-cause death (RR = 0.87 (95% CI, 0.80-0.94)), major bleeding (RR = 0.84; (95% CI, 0.74-0.97)), intracranial hemorrhage (RR = 0.50; 95% CI, 0.43-0.59), and hemorrhagic stroke (RR = 0.49 (95% CI, 0.38-0.63)). There were no differences in the risks of ischemic stroke (RR = 0.89 (95% CI, 0.75-1.04)) and gastrointestinal bleeding (RR = 1.11 (95% CI, 0.79-1.55)) in patients treated with NOACs versus warfarin. Compared with warfarin use, the use of NOACs had similar or lower risks of thromboembolic and bleeding events in patients with AF and HF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Stroke; Treatment Outcome; Warfarin

Despite advances in medical and device therapy, patients with heart failure remain at high risk for morbidity and mortality. Experimental and clinical studies have shown an association between heart failure and a hypercoagulable state, and that patients with heart failure experience an increased incidence of stroke and other thromboembolic events, regardless of whether they are in atrial fibrillation. Although oral anticoagulation is recommended when atrial fibrillation is present, the benefits of this therapy in patients with heart failure in sinus rhythm are uncertain. Older randomized controlled trials comparing warfarin with antiplatelet therapy were, for the most part, underpowered and failed to show convincing benefits of warfarin therapy in this population. Several recent studies that assessed the effects of low-dose direct-acting oral anticoagulant therapy in patients with coronary artery disease in sinus rhythm either included or specifically targeted patients with heart failure. Post hoc analysis of their results showed that this treatment strategy was associated with improved outcomes in patients with acute coronary syndrome or stable coronary artery disease and also a significant reduction in thromboembolic events, including ischemic stroke. This review presents the rationale for anticoagulant therapy in patients with heart failure in sinus rhythm, discusses gaps in our knowledge base, offers suggestions for when anticoagulation might be considered, and identifies potential directions for future research.

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Failure; Humans; Thromboembolism; Warfarin

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

To recommend the proper anticoagulant drug and its dose for patients with atrial fibrillation (AF) and heart failure (HF), we conducted a network meta-analysis (NMA) to make the comparisons among non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin with regard to efficacy (stroke or systemic embolism) and safety (major bleeding).. We searched PubMed, EMBASE, Web of Science and Cochrane Library with the items: "dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, atrial fibrillation and heart failure" through April 14, 2020, focusing on the RCTs comparing the effect of NOACs to warfarin in patients with AF and HF. The NMA was performed based on R (version3.5.1) recalling JAGS (version4.3.0) with gemtc package. Moreover, NetMetaXL (version1.6.1) and winBUGS (version1.4.3) were employed to obtain the cumulative ranking curve area (SUCRA) of the anticoagulants.. There was a high probability that dabigatran150 (SUCRA 0.82) ranked the first for the most effective drug, followed by apixaban (SUCRA 0.81), edoxaban60 (SUCRA 0.57) and rivaroxaban (SUCRA 0.52). However, with respect to safety for preventing major bleeding, edoxaban30 (SUCRA 0.99) ranked as the safest drug, followed by apixaban (SUCRA 0.71), edoxaban 60 (SUCRA 0.59) and dabigatran150 (SUCRA 0.55).. Apixaban, edoxaban60 and dabigatran150 were more likely to become the choice for preventing stroke or systemic embolism and major bleeding in patients with AF and HF. Nevertheless, more trials need to be performed to focus on the effect of NOACs on the efficacy outcome due to the sparse data. In addition, caution should be excised over selecting the NOAC and its dose on account of the lacking head-to-head comparisons.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Heart Failure; Humans; Network Meta-Analysis; Pyridones; Rivaroxaban; Stroke; Warfarin

Continuous-flow left ventricular assist devices (CF-LVADs) prolong survival in advanced heart failure patients. Anticoagulation control is critical in CF-LVAD patients due to increased thromboembolic and bleeding risk. We assessed the quality of INR control in CF-LVAD patients measured by time in therapeutic range (TTR). We performed a systematic literature search of MEDLINE and SCOPUS through July 2017 to identify studies evaluating TTR in anticoagulated adult CF-LVAD patients. Data on key characteristics and the TTR end point were then extracted from each study by two investigators using a standardized tool. Using a Hartung-Knapp random effects model, a weighted mean TTR estimate with accompanying 95% confidence interval (CI) was calculated. Statistical heterogeneity was estimated using the I

Topics: Anticoagulants; Blood Coagulation; Heart Failure; Heart-Assist Devices; Humans; Thrombosis; Warfarin

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors. The European Society of Cardiology has very recently introduced a third HF subtype entitled HF with mid-range ejection fraction (HFmrEF). At present oral anticoagulation is recommended for all patients with AF and HF, independent of HF type. In addition to warfarin there are currently four non-vitamin K oral anticoagulants (NOACs, previously called novel oral anticoagulants) that have been approved for the prevention of SSE. They consist of one direct thrombin inhibitor, dabigatran and three factor Xa inhibitors: rivaroxaban, apixaban and, most recently, edoxaban. In this review article we present an overview of the evidence to support the use of NOACs for the prevention of SSE in patients with AF and HF and review the influence of HF subtype and co-morbidities on the potential choice of oral anticoagulant.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Dabigatran; Drug Therapy, Combination; Factor Xa Inhibitors; Heart Failure; Humans; Stroke Volume; Treatment Outcome; Warfarin

Current evidence indicates that heart failure (HF) confers a hyper-coagulable state that is associated with adverse events including stroke, systemic embolism, and mortality. This may be due to the elevated levels of pro-thrombotic and pro-inflammatory cytokines that are seen in patients with acute and chronic HF. Left ventricular wall motion abnormalities in patients with systolic dysfunction predispose to local thrombosis due to blood stasis as does atrial fibrillation (AF) which leads to blood stasis in regions of the atria. The high risk of thromboemboli in HF patients with AF has resulted in the use anticoagulation therapy to prevent the occurrence of catastrophic events. There is evidence, however, that the pro-inflammatory, pro-thrombotic state that exists in HF puts patients who are in sinus rhythm at risk. The novel oral anticoagulants (NOACs) have been shown in RCT to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding. The fact that the NOACs don't require routine monitoring to assure that patients remain within the therapeutic range and have relatively simple dosing requirements and a safer risk profile makes them attractive substitutes to warfarin in HF patients with atrial fibrillation and other conditions (e.g. deep venous thrombosis). Post hoc analyses from a subset of HF patients from the RCTs in AF patients have demonstrated similar findings as were reported in the entire populations that were included in the trials. As a result, NOACS are commonly used now in HF patients with AF. For HF patients with reduced ejection fraction in sinus rhythm, the use of warfarin in randomized clinical trials (RCT) to reduce stroke has been disappointing and associated with increase bleeding risk when compared to aspirin. The advantages of the NOACs over warfarin, however, raise the question of whether they might improve outcomes in HF patients who are in sinus rhythm. The currently ongoing COMMANDER-HF trial has been designed to address this issue. In this chapter we review evidence of existence of a prothombotic state in HF, the pharmacodynamics and clinical trials of the NOACs and the outcomes from NOAC substudies in the HF subgroup. We also discuss the rationale for using anticoagulation in HF independent of arrhythmia burden.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Creatinine; Diabetes Complications; Drugs, Investigational; Europe; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Myocardial Infarction; North America; Observational Studies as Topic; Pyrazoles; Pyridones; Registries; Renal Insufficiency, Chronic; Severity of Illness Index; Stroke; Tachycardia; Thrombophilia; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder, and increases in prevalence with increasing age and the number of cardiovascular comorbidities. AF is characterized by a rapid and irregular heartbeat that can be asymptomatic or lead to symptoms such as palpitations, dyspnoea and dizziness. The condition can also be associated with serious complications, including an increased risk of stroke. Important recent developments in the clinical epidemiology and management of AF have informed our approach to this arrhythmia. This Primer provides a comprehensive overview of AF, including its epidemiology, mechanisms and pathophysiology, diagnosis, screening, prevention and management. Management strategies, including stroke prevention, rate control and rhythm control, are considered. We also address quality of life issues and provide an outlook on future developments and ongoing clinical trials in managing this common arrhythmia.

Topics: Ablation Techniques; Anticoagulants; Aspirin; Atrial Fibrillation; Dizziness; Dyspnea; Electric Countershock; Flecainide; Heart Failure; Heart Rate; Humans; Hypertension; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prevalence; Propafenone; Quality of Life; Risk Factors; Sodium Channel Blockers; Stroke; Thromboembolism; Warfarin

This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis.. AF is quite prevalent in patients with HF.. Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included. Each patient was defined as affected by HF according to the criteria of the trial in which the patient was enrolled. Pre-specified outcomes were the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular (CV) and all-cause death.. A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and 28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin (median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE (relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68) and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95% CI: 0.81 to 0.91; p < 0.01) and intracranial (RR: 0.74 95% CI: 0.63 to 0.88; p < 0.01) bleeding but increased rates of all-cause (RR: 1.70 95% CI: 1.31 to 2.19; p < 0.01) and CV death (RR: 2.05 95% CI: 1.66 to 2.55; p < 0.01). NOACs, compared with warfarin significantly reduced SSE and major, intracranial, and any bleeding, regardless of the presence or absence of HF (p. Patients with AF and HF had increased mortality but reduced rates of intracranial and any bleeding compared with the no-HF patients, with no differences in rates of SSE and major bleeding. NOACs significantly reduced SSE, major bleeding, and intracranial hemorrhage in HF patients. No interactions in efficacy and safety of NOACs were observed between AF patients with and without HF.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Dabigatran; Embolism; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

No pooled analysis has been undertaken to assess the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized controlled trials (RCTs).. Comprehensive literature searches were conducted using the Cochrane Library, MEDLINE, and Scopus databases from inception to April 2015. Statistical analyses were performed using RevMan 5.3 software.. Four RCTs were included: 19 122 of 32 512 AF patients with HF were allocated to a NOAC (13 384 receiving single-/high-dose NOAC regimens), and 13 390 to warfarin. Among AF patients with HF, single/high-dose NOACs significantly reduced the risk of stroke/systemic embolic (SE) events by 14% [odds ratio0.86, 95% confidence interval (CI) 0.76-0.98), and had a 24% lower risk of major bleeding(OR 0.76, 95% CI 0.67-0.86). For low-dose NOAC regimens, comparable efficacy to warfarin for stroke or SE events (OR 1.02, 95% CI 0.86-1.21) and a non-significant trend for lower major bleeding was observed. Regardless of high- or low-dose NOAC, the incidences of both major bleeding and stroke/SE in AF patients with HF were similar to those without HF. Atrial fibrillation patients with HF on NOACs had a 41% lower risk of intracranial haemorrhage compared with those without HF (OR 0.59, 95% CI 0.40-0.87).. Among AF patients with HF, single-/high-dose NOAC regimens have a better efficacy and safety profile, but low-dose regimens had similar efficacy and safety to warfarin. NOACs were similarly effective or even safer (less intracranial haemorrhage) in AF patients with HF compared with those without HF.

Topics: Anticoagulants; Atrial Fibrillation; Heart Failure; Hemorrhage; Humans; Pyridines; Randomized Controlled Trials as Topic; Risk Adjustment; Stroke; Thiazoles; Treatment Outcome; 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

Due to the narrow therapeutic range and high drug-to-drug interactions (DDIs), improving the adequate use of warfarin for the elderly is crucial in clinical practice. This study examines whether the effectiveness of using warfarin among elderly inpatients can be improved when machine learning techniques and data from the laboratory information system are incorporated.. Having employed 288 validated clinical cases in the DDI group and 89 cases in the non-DDI group, we evaluate the prediction performance of seven classification techniques, with and without an Adaptive Boosting (AdaBoost) algorithm. Measures including accuracy, sensitivity, specificity and area under the curve are used to evaluate model performance.. Decision tree-based classifiers outperform other investigated classifiers in all evaluation measures. The classifiers supplemented with AdaBoost can generally improve the performance. In addition, weight, congestive heart failure, and gender are among the top three critical variables affecting prediction accuracy for the non-DDI group, while age, ALT, and warfarin doses are the most influential factors for the DDI group.. Medical decision support systems incorporating decision tree-based approaches improve predicting performance and thus may serve as a supplementary tool in clinical practice. Information from laboratory tests and inpatients' history should not be ignored because related variables are shown to be decisive in our prediction models, especially when the DDIs exist.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Artificial Intelligence; Body Weight; Clinical Laboratory Information Systems; Comorbidity; Cross-Cultural Comparison; Decision Trees; Dose-Response Relationship, Drug; Drug Interactions; Ethnicity; Female; Heart Failure; Humans; Male; Medical History Taking; Middle Aged; Quality Improvement; Risk Factors; Taiwan; Thyrotoxicosis; Warfarin

To review the thromboembolic risk, pathophysiology associated with the risk, and literature investigating the use of antithrombotics in patients with heart failure with reduced ejection fraction and normal sinus rhythm (HFrEF-NSR).. An English language literature search was performed with MEDLINE/PubMed and Embase from January 1950 to October 2013 using the search terms heart failure, HFrEF, systolic heart failure, cardiomyopathy, left ventricular dysfunction, sinus rhythm, thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, acute coronary events, coronary artery disease, stroke, and cerebrovascular events to identify relevant articles. References in the retrieved articles were also assessed to identify other important articles.. All pertinent original studies, reviews, consensus documents, and guidelines were evaluated for inclusion.. Patients with HFrEF-NSR may be predisposed to developing thromboembolic events. Studies that have examined the role of antithrombotics (warfarin and/or antiplatelet therapy) for reducing thromboembolic risk have been inconclusive. The WASH and HELAS pilot trials--the only studies with a no-antithrombotics or placebo comparator group--did not find a benefit with antithrombotic therapy but found an increased risk of bleeding with warfarin and of hospitalizations with aspirin. Although the clinical outcome studies (WATCH and WARCEF) suggested that warfarin may reduce stroke risk compared with antiplatelet therapy, the lack of a placebo group and lower-than-projected enrollment prevents definitive conclusions from being made.. Current evidence does not support the routine use of antithrombotics for preventing thromboembolic events in patients with HFrEF-NSR without compelling indications.

Topics: Anticoagulants; Aspirin; Heart Failure; Humans; Platelet Aggregation Inhibitors; Thromboembolism; Ventricular Dysfunction, Left; 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

There is clinical equipoise between warfarin and aspirin for stroke prevention in patients with heart failure in sinus rhythm (SR). The objective of this meta-analysis was to pool risk estimates for stroke, mortality, and intracerebral hemorrhage (ICH) from published clinical randomized controlled trials (RCTs).. MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched for English-language RCTs comparing warfarin to aspirin in heart failure through May 2012. Pooled relative risk (RR) was calculated from a random-effects model.. Four RCTs (n=3681) met the criteria for study inclusion. Warfarin was associated with a lower risk of stroke compared with aspirin (pooled RR, .59; 95% confidence interval [CI], .41-.85; P=.004). The number needed to treat (NNT) was 61. There was no difference between warfarin and aspirin in mortality (pooled RR, 1; 95% CI, .88-1.13), and ICH (pooled RR, 2.17; 95% CI, .76-6.24). Among secondary outcomes, warfarin was associated with almost twice the risk of major hemorrhage (pooled RR, 1.95; 95% CI, 1.37-2.76; P=.0001) compared with aspirin. The number needed to harm (NNH) was 34. There was no significant difference between warfarin and aspirin in risk of myocardial infarction (MI) (pooled RR, 1.02; 95% CI, .65-1.6], and heart failure exacerbation (HFE) (pooled RR, 1.11; 95% CI, .76-1.63).. Compared with aspirin, warfarin reduced the risk of stroke while conferring an increased risk of major hemorrhage. Warfarin does not increase mortality or confer an increased risk of ICH compared with aspirin.

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Warfarin

The risk-benefit profile of warfarin versus aspirin for patients with heart failure in normal sinus rhythm has not been definitively established. Our objective was to evaluate the overall comparative effects of warfarin and aspirin in patients with heart failure and normal sinus rhythm.. Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from January 1966 to June 2012 were searched to identify relevant studies. We included randomized controlled trials that included comparison of warfarin versus aspirin, and composite end point of death or stroke separately for active treatment and control groups. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects models. The search identified 4 randomized controlled trials of warfarin versus aspirin therapy, enrolling 3663 patients. There was no significant difference between the 2 treatments for the primary end point (warfarin versus aspirin: RR, 0.94; 95% CI, 0.84-1.06; P=0.31). Warfarin (versus aspirin) was associated with lower risk of any stroke (RR, 0.56; 95% CI, 0.38-0.82; P=0.003) and ischemic stroke (RR, 0.45; 95% CI, 0.24-0.86; P=0.02) but had a neutral effect on death (RR, 1.01; 95% CI, 0.89-1.14; P=0.89) and a higher risk of major bleeding (RR, 1.95; 95% CI, 1.37-2.76; P=0.0002).. Compared with aspirin, warfarin does not provide benefit in the prevention of stroke and death among patients with heart failure in sinus rhythm, but raises the risk of major bleeding; and therefore its use in these patients is not justified.

Topics: Anticoagulants; Aspirin; Chi-Square Distribution; Female; Fibrinolytic Agents; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Patient Selection; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated.. We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm. MEDLINE, Web of Science, CENTRAL and Scopus databases were searched up to May 2012. Four RCTs were identified and a total of 3663 patients were included in the meta-analysis. Patients with both ischemic and non-ischemic HF were included. There was no significant difference in mortality (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.86 to 1.19) between OATs group and antiplatelet drug group. OATs have reduced ischemic stroke risk (OR 0.49, 95% CI 0.32 to 0.74), but have increased major bleeding risk (OR 2.01, 95% CI 1.40 to 2.88) compared to antiplatelet treatment.. In HF patients in sinus rhythm OATs do not show a better risk-benefit profile compared to antiplatelet treatment in cardioembolism prevention. Warfarin and aspirin seem to be similar in reducing mortality. Warfarin reduces the incidence of ischemic stroke, but increases major bleedings. Thus, it is possible to speculate that aspirin prescription be indicated in patients with high risk of bleeding, whereas warfarin could be preferred in patients with high thromboembolic risk.

Topics: Administration, Oral; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Fibrinolytic Agents; Heart Failure; Humans; Odds Ratio; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Warfarin

Warfarin is widely prescribed for patients with atrial fibrillation. In addition to unexpected bleeding, allergic skin reaction is one of its uncommon adverse effects. We herein report an 89-year-old man who, after taking warfarin for 4 years, suffered extensive skin eruptions. The skin biopsy disclosed leukocytoclastic vasculitis. The causal relationship between skin lesions and warfarin was confirmed after re-challenge of warfarin. A literature review revealed only 13 such cases reported from 1980 to 2011. Clinicians should be aware of this potential adverse effect of warfarin.

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Coronary Disease; Drug Eruptions; Heart Failure; Humans; Hypertension; Male; Proteinuria; Taiwan; Thrombophilia; Vasculitis, Leukocytoclastic, Cutaneous; Warfarin

Chronic heart failure (HF) with either reduced or preserved ejection fraction is common and remains an extremely serious disorder with a high mortality and morbidity. Many complications related to HF can be related to thrombosis. Epidemiological and pathophysiological data also link HF to an increased risk of thrombosis, leading to the clinical consequences of sudden death, stroke, systemic thrombo-embolism, and/or venous thrombo-embolism. This consensus document of the Heart Failure Association (EHFA) of the European Society of Cardiology (ESC) and the ESC Working Group on Thrombosis reviews the published evidence and summarizes 'best practice', and puts forward consensus statements that may help to define evidence gaps and assist management decisions in everyday clinical practice. In HF patients with atrial fibrillation, oral anticoagulation is recommended, and the CHA(2)DS(2)-VASc and HAS-BLED scores should be used to determine the likely risk-benefit ratio (thrombo-embolism prevention vs. risk of bleeding) of oral anticoagulation. In HF patients with reduced left ventricular ejection fraction who are in sinus rhythm there is no evidence of an overall benefit of vitamin K antagonists (e.g. warfarin) on mortality, with risk of major bleeding. Despite the potential for a reduction in ischaemic stroke, there is currently no compelling reason to use warfarin routinely for these patients. Risk factors associated with increased risk of thrombo-embolic events should be identified and decisions regarding use of anticoagulation individualized. Patient values and preferences are important determinants when balancing the risk of thrombo-embolism against bleeding risk. New oral anticoagulants that offer a different risk-benefit profile compared with warfarin may appear as an attractive therapeutic option, but this would need to be confirmed in clinical trials.

Topics: Aspirin; Confidence Intervals; Europe; Fibrinolytic Agents; Heart Failure; Humans; Platelet Aggregation Inhibitors; Prognosis; Risk Factors; Thromboembolism; Warfarin

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Azetidines; Cardiomyopathies; Ezetimibe; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Risk; Seizures; Simvastatin; Ultrasonography; 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 emergence of new oral anticoagulants is a major development in cardiovascular medicine. In this overview, we sought to evaluate the impact of gender, heart failure, paroxysmal atrial fibrillation (AF) and diabetes on stroke prevention with warfarin and the new oral anticoagulants by conducting a semisystematic review and meta-analysis including 44,563 patients in recent contemporary Phase III trials. The new oral anticoagulants were superior to warfarin irrespective of gender or the presence of diabetes. For nonparoxysmal AF, event rates are similar with warfarin and new anticoagulants. There is some suggestion of the benefit of new oral anticoagulants in patients with paroxysmal AF. For patients without heart failure, the new drugs are superior, whereas in patients with evidence of heart failure the new drugs were similar to warfarin. In conclusion, new oral anticoagulants are better than warfarin irrespective of gender or the presence of diabetes mellitus. Patients with heart failure and nonparoxysmal AF seem not to gain additional prognostic benefit from new anticoagulants.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Female; Heart Failure; Humans; Male; Risk Factors; Sex Factors; Stroke; 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

Atrial fibrillation (AF) and heart failure (HF) are the emerging epidemics of cardiovascular disease in the new millennium. Both are responsible for considerable morbidity and mortality and health budget expenditure. The advent of catheter ablation for patients with AF has provided important new insights into the relative contribution of AF to left ventricular dysfunction. The aim of this review is to discuss the complex interplay in the pathophysiology of AF and HF to improve our understanding of the basis for current treatment strategies and guide future research direction.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electrocardiography; Heart Failure; Humans; Middle Aged; Warfarin

Peripartum cardiomyopathy is a life-threatening condition of unknown cause that occurs in previously healthy women during the peripartum period. It is characterized by left ventricular dysfunction and symptoms of heart failure that can arise in the last trimester of pregnancy or up to 5 months after delivery. We review its possible causes and how to recognize and manage it.

Topics: Abnormalities, Drug-Induced; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiomyopathies; Contraindications; Female; Heart Failure; Heart Transplantation; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Recurrence; Risk Factors; Ventricular Dysfunction, Left; Warfarin

The existing guidelines for the treatment of patients who have heart failure limit the administration of antiplatelet and anticoagulant agents to patients who have specific comorbidities, including coronary artery disease, atrial fibrillation, history of thromboembolic events, and left ventricular mural thrombus. Retrospective analyses of large clinical trials or smaller nonrandomized studies indicate that the use of statins may be beneficial both in ischemic and idiopathic dilated cardiomyopathy. This article outlines the current knowledge regarding the use of antiplatelet and anticoagulant agents and statins in patients who have heart failure.

Topics: Anticoagulants; Aspirin; Drug Administration Schedule; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Platelet Aggregation Inhibitors; Warfarin

The risk of thromboembolic events in heart failure patients is estimated to be in the range of 1-4.5% per year. To date, there are insufficient data to guide us in appropriate use of antithrombotic or antiplatelet drug therapy to decrease the risk of events in this population. This review will outline the existing literature on anticoagulation and heart failure.. Until recently, no randomized controlled data existed to identify the risks and benefits of anticoagulation in heart failure patients. Three recent trials have attempted to shed light on this topic. Unfortunately, these studies have been of limited value due to poor recruitment and are underpowered to definitively answer these questions.. Until additional randomized control data are available, the routine use of anticoagulation for heart failure patients cannot be advocated. Limited data suggest that the benefits of anticoagulation may outweigh the risks in the following categories: ejection fraction less than 20%; left ventricular systolic dysfunction and history of previous stroke; and known thrombus in the left or right ventricle. We eagerly await the completion of the Warfarin Aspirin Reduced Cardiac Ejection Fraction Study.

Topics: Anticoagulants; Aspirin; Heart Failure; Humans; Platelet Aggregation Inhibitors; Risk Factors; Thromboembolism; Treatment Outcome; Warfarin

Chronic heart failure (CHF) is traditionally associated with increased risk of thromboembolic complications. Key features of CHF pathophysiology, such as impairment of intracardiac hemodynamics, peripheral blood flow deceleration, neuroendocrine activation, chronic oxidative stress and proinflammatory changes, could explain the predisposition to thromboembolism. However, conclusive epidemiologic data on thromboembolic event incidence in CHF are lacking. Furthermore, the place of antithrombotic therapy in CHF management is still uncertain. Apart from established indications for warfarin (e.g. atrial fibrillation and previous embolic events), there is no robust evidence to support administration of vitamin K antagonists to other patients with CHF, particularly to patients in sinus rhythm. The role of aspirin in preventing thromboembolism in these patients is also controversial. Large randomized trial data on the effectiveness and risks of warfarin and aspirin use in CHF patients with sinus rhythm are forthcoming. This article provides a brief overview of the epidemiologic and pathobiological background of thromboembolism in CHF, and discusses the up-to-date clinical evidence on antithrombotic therapy in detail.

Topics: Anticoagulants; Aspirin; Heart Failure; Humans; Thromboembolism; Warfarin

Topics: Cardiac Catheterization; Cardiac Surgical Procedures; Diagnostic Imaging; Digitalis Glycosides; Diuretics; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Mitral Valve Stenosis; Rheumatic Fever; Warfarin

Topics: Anticoagulants; Cardiac Output; Cerebral Infarction; Cerebrovascular Circulation; Heart Failure; Humans; Stroke Volume; Warfarin

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiac Surgical Procedures; Echocardiography, Transesophageal; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Hyperthermia, Induced; Mitral Valve Insufficiency; Ventricular Remodeling; Warfarin

Numerous factors, such as other drugs, diet, and age, are well documented as altering response to warfarin. Less attention has been focused on the effect of disease states on the response to oral anticoagulants. Decompensated heart failure is reported to increase response to warfarin, but documentation is limited.. The purpose of this review is to critically examine the evidence of a possible effect of heart failure exacerbations on response to warfarin.. A literature search was completed of the last 60 years using several databases, including PubMed, MEDLINE, EMBASE, and SCOPUS. Key terms in our search included 'warfarin' AND 'heart failure' and 'heart failure exacerbation' (or 'decompensated heart failure') AND 'effect on warfarin'. When relevant citations were found, the references cited by those authors were checked.. Several reports from 1946-1989 suggested that decompensated heart failure increases response to oral anticoagulants. Unfortunately, these early reports have important limitations. More recent reports, since the widespread use of the international normalized ratio (INR), also suggest that heart failure exacerbations are associated with increased response to warfarin. Patient populations are small in these reports.. Heart failure exacerbations may be associated with an increased response to warfarin and other vitamin K antagonists, but many reports are inadequate, and it appears that not all patients are susceptible to this effect. More frequent monitoring of INR in patients with decompensated heart failure is warranted. It is prudent to initiate warfarin at lower doses in patients with a history of heart failure and to monitor INR every 1-2 weeks during times of instability in ambulatory patients, and daily INRs in hospitalized patients. Given the large number of variables that impact on warfarin dose requirement, it is difficult to clearly establish the effect of decompensated heart failure on response to warfarin. Further studies must take all of these variables into account.

Topics: Anticoagulants; Heart Failure; Humans; International Normalized Ratio; 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

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta-analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD-HeFT study showed that ICD therapy reduced all-cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.

Topics: Anticoagulants; Cardiology; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Meta-Analysis as Topic; Myocardial Infarction; Pacemaker, Artificial; Piperidines; Platelet Aggregation Inhibitors; Pyrazoles; Rimonabant; United States; Warfarin

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Spironolactone; Warfarin

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Spironolactone; Warfarin

Incidence data on thromboembolism in patients with heart failure (which may include stroke, peripheral embolism, pulmonary embolism) are limited but provide a general population range from 1-5 cases per 1000 each year, increasing with age to more than 30 cases per 1000 each year among people aged 75 years or older. However, the incidence of thromboembolism varied depending very much on what was being investigated in each of these studies. Data from subgroup analysis of the larger heart failure trials would seem to support this incidence data, although there is very little true epidemiological data and no randomised, controlled trial has been designed to specifically investigate thromboembolism in patients with heart failure. 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 investigate if oral anticoagulation is of benefit for the prevention of thromboembolism in patients with heart failure. The use of warfarin therapy for heart failure patients has been a controversial subject. Warfarin does have a role to play in patients with myocardial infarction and those with atrial fibrillation. Furthermore, in patients with congestive heart failure secondary to coronary artery disease, warfarin reduces the occurrence of nonfatal myocardial infarction and, therefore, may reduce the chances of progression to heart failure. It has also been shown that warfarin reduces the risk of thromboembolic strokes in patients recovering from myocardial infarction. At present, there is a lack of randomised data, and the incidence of bleeding complications in patients with heart failure has caused a decrease in the use of oral anticoagulants for the prevention of thrombosis. This review summarises the incidence, potential mechanism and therapeutic approaches for management of thromboembolism in heart failure.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Heart Failure; Heparin, Low-Molecular-Weight; Humans; Thromboembolism; Thrombophilia; Warfarin

The American College of Cardiology provided much useful new information to inform those who care for patients with heart failure about what they should and should not adopt into current clinical practice. The EPHESUS trial suggests a much wider role for aldosterone antagonists for the management of heart failure and left ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer, simpler warfarin substitute soon. ASCOT reinforces the potential futility of statin therapy unless it is well targeted. The results of the COMPANION study investigating cardiac resynchronisation devices and implantable defibrillators were encouraging but inconclusive and/or hard to interpret. UK-PACE again questions the use of dual chamber pacing. T-wave alternans is an interesting experimental technique that may be useful in selecting which patients need an implantable defibrillator, although the technology needs testing in an appropriate patient population.

Topics: Anticoagulants; Cardiac Pacing, Artificial; Defibrillators, Implantable; Electrocardiography; Eplerenone; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Spironolactone; Ventricular Dysfunction, Left; Warfarin

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Warfarin

Atrial fibrillation occurs commonly in the setting of congestive heart failure and, in fact can cause left ventricular dysfunction due to a rapid ventricular response over time, termed tachycardia-mediated cardiomyopathy. The combination of atrial fibrillation and congestive heart failure leads to a high risk of stroke for the patient and appropriate antithrombotic therapy can minimize this incidence of stroke. Stroke risk can be markedly reduced by treatment with warfarin and complications of anticoagulation minimized by close attention to maintaining the INR between 2.0 and 3.0.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Middle Aged; Prognosis; Stroke; Warfarin

The risk of thromboembolism in chronic heart failure and the risk-to-benefit ratio of anticoagulation in this population are poorly defined.. A PubMed/MEDLINE search of published trials was performed. Twenty-four studies were identified after exclusion of individual case reports. All studies were prospective or retrospective observational reports, either independent studies or secondary analyses of prospective clinical trials in patients with heart failure. Prevalence estimates ranged of thromboemboli ranged from 3% to 50% and incidence estimates ranged from 1.5 to 3.5/100 patient-years. Although no randomized data of therapeutic anticoagulation were identified, a secondary analysis of one study suggested event reduction in patients receiving warfarin anticoagulation; other studies failed to suggest such benefit. Overall bleeding estimates in warfarin-treated patients ranged from 2.3 to 6.8/100 patient-years. Intracranial hemorrhage rates were 0.62 to 0.9/100 patient-years but increased with age. Only one study suggested that aspirin was beneficial in reducing clinically significant emboli.. Although patients with chronic heart failure and left ventricular dilation have a higher risk of thromboembolism, data are insufficient to recommend warfarin or aspirin prophylaxis in the absence of additional indications for such therapy.

Topics: Anticoagulants; Aspirin; Cardiomyopathy, Dilated; Heart Failure; Humans; Incidence; Thromboembolism; Warfarin

Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, and 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 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.. Systematic review.. Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data.. Randomized controlled trials (RCTs) comparing oral anticoagulants with control or placebo. Non-randomized studies were included, as they may help in assessing side-effects. Other inclusion criteria included duration of treatment > or =1 month, and adults with heart failure due to any underlying cause. Inclusion decisions were duplicated, and disagreement resolved by discussion or a third party.. One recent pilot RCT compared warfarin, aspirin and no antithrombotic therapy, but no definitive data have yet been published. Three small prospective studies of warfarin in heart failure were also identified, but were over 50 years old, with methods considered unreliable today: in these, anticoagulation was more efficacious than control in reducing all-cause death (OR 0.64; 95%CI 0.45-0.90) and cardiovascular events (OR 0.26; 95%CI 0.16-0.43). Four retrospective non-randomized cohort analyses and three small observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients, and reported contradictory results.. Limited evidence from randomized trials and observational studies found a reduction in mortality and cardiovascular events with anticoagulants compared to controls. This evidence should be interpreted with caution. Although oral anticoagulation is indicated in certain groups of patients with heart failure (e.g. atrial fibrillation), the available data do not support its routine use in heart failure patients who remain in sinus rhythm.

Topics: Anticoagulants; Heart Failure; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Warfarin

Heart failure predisposes to stroke and thromboembolism, which in turn contribute to the high mortality and morbidity in heart failure.. To determine the effect of antiplatelet agents, compared to placebo or anticoagulant therapy, on death and/or major thromboembolic events in adults with heart failure who are in sinus rhythm.. Systematic review of randomized parallel group placebo or controlled trials comparing oral antiplatelet therapy with control or anticoagulation therapy in adults with chronic heart failure in sinus rhythm.. Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data.. These included duration of treatment of at least 1 month, and adults with heart failure due to any underlying cause. To assess any adverse effects, cohort study and non-randomized controlled studies were assessed. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. No meta-analyses were performed, as no data were available from randomized comparisons.. One randomized controlled trial of warfarin vs. aspirin vs. no antithrombotic therapy was found, but no definitive data have yet been published. Three retrospective, non-randomized cohort studies from large trials examining the role of ACE inhibitors have examined the role of aspirin therapy with and without anticoagulant therapy in patients with heart failure and/or left ventricular systolic dysfunction were identified, but the results from these trials were conflicting. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is from retrospective analyses of trial cohorts.. At present there is no evidence from long term RCTs to recommend use of aspirin to prevent thromboembolism in patients with heart failure in sinus rhythm. There is also no evidence to indicate superior effects from oral anticoagulation, when compared to aspirin, in patients with heart failure in sinus rhythm.

Topics: Adult; Anticoagulants; Aspirin; Heart Failure; Humans; Platelet Aggregation Inhibitors; Thromboembolism; Treatment Outcome; Warfarin

There are no clear data regarding whether to use warfarin, aspirin, or no therapy in patients with left ventricular systolic dysfunction. Aspirin use is widespread in patients with vascular disease but it can decrease renal blood flow in low output states. Warfarin may be used in patients with advancing heart failure due to the perceived risk of in situ thromboembolism. However, we know that ejection fraction and symptom class do not always match and that the regulation of warfarin dosing is more difficult in worsening heart failure. Drug use must be individualized, based on knowledge of underlying heart failure etiology, functional class, drug side effects, and renal function. We await ongoing studies to elucidate the differential effects of these drugs on global outcome as well as on the mechanisms by which they achieve their results.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Heart Failure; Humans; Platelet Aggregation Inhibitors; Thromboembolism; Ventricular Dysfunction, Left; Warfarin

The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class declines. The interactions of aspirin and ACE inhibitors have been best evaluated for the hemodynamic effects. There may be additional factors hitherto not studied. The hemodynamic effect of ACE inhibitors may be more important in NYHA classes III and IV than in less symptomatic patients. Warfarin use has clear indications for patients in atrial fibrillation with mechanical prosthetic valves, in hypercoagulable states, and with a previous history of embolization. Aspirin is inexpensive and commo

Topics: Anticoagulants; Cardiomyopathies; Comorbidity; Heart Failure; Humans; Life Style; Stroke; Ventricular Dysfunction, Left; Warfarin

Warfarin is associated with numerous drug and food interactions, and much attention has been appropriately focused on this subject. Because several disease states may also affect response to oral anticoagulants, we present a summary of the literature.. We searched MEDLINE for original articles on the effect of disease states on response to warfarin.. Liver disease and thyroid dysfunction are well-documented as affecting warfarin response. Further study is needed to establish whether febrile illness, congestive heart failure, and other disease states enhance the effect of warfarin in some patients.. Careful monitoring of anticoagulant therapy in patients with diseases that have the potential to affect warfarin response could increase safety and efficacy of this important agent.

Topics: Administration, Oral; Anticoagulants; Disease; Drug Interactions; Drug Monitoring; Fever; Food-Drug Interactions; Heart Failure; Humans; Liver Diseases; Safety; Thyroid Diseases; Warfarin

Knowledge of the pathogenesis of congestive heart failure (CHF) has improved greatly in recent years. However, this disease continues to cause one of the highest morbidities and mortalities in the Western world. The pathophysiology of heart failure is complex and much of our understanding revolves strictly around the neurohormonal mechanisms involved. Various pharmacologic interventions have significantly improved morbidity and include ACE inhibitors, beta-blockers, diuretics, and inotropic agents. Yet, no consensus has been reached regarding the use of anticoagulants or antiplatelet agents. It has been suggested that CHF is associated with altered hemostasis, but whether this prothrombotic state contributes to the pathogenesis and progression of the disease is unknown. The purpose of this review article is to discuss our current knowledge of platelet activation, thrombin generation, fibrinolysis, and endothelial dysfunction in CHF patients, and the potential role of anticoagulants and/or antiplatelet agents in preventing these hemostatic abnormalities.

Topics: Anticoagulants; Biomarkers; Clinical Trials as Topic; Endothelins; Fibrinolysis; Fibrinolytic Agents; Heart Failure; Hemostasis; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Retrospective Studies; Thrombin; Thromboembolism; Warfarin

Despite the remarkable advances in cardiovascular therapeutics over the past four decades, little impact has been made on either the incidence or mortality rate of congestive heart failure and it remains a major clinical and public health problem. Recent practice audits have suggested that proven efficacious therapies are not maximally applied in patients with this condition. An approach to the patient with congestive heart failure is presented, emphasizing the two distinct syndromes of systolic dysfunction and diastolic dysfunction. Treatment recommendations are derived from consideration of the underlying pathophysiology and the evidence from randomised clinical trials.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Trials as Topic; Diet, Sodium-Restricted; Diuretics; Drinking; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Prevalence; Risk Factors; Severity of Illness Index; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Warfarin

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Coronary Disease; Drug Interactions; Heart Failure; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

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

Topics: Age Factors; Anticoagulants; Arrhythmias, Cardiac; Coumarins; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Phenindione; Prothrombin Time; Shock; Time Factors; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Drug Therapy, Combination; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Warfarin

There is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial.. We performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131).. The presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM.

Topics: Aged; Anticoagulants; Aspirin; Cardiomyopathies; Cause of Death; Defibrillators, Implantable; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Propensity Score; Radionuclide Ventriculography; Retrospective Studies; Risk Factors; Stroke Volume; Survival Rate; United States; Ventricular Function, Left; Warfarin

Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.. The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.. In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.. Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cause of Death; Death, Sudden, Cardiac; Double-Blind Method; Factor Xa Inhibitors; Female; Growth Differentiation Factor 15; Heart Failure; Hemorrhage; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Troponin T; Warfarin

Previous studies in patients with atrial fibrillation showed that a history of heart failure (HF) could negatively impact anticoagulation quality, as measured by the average time in therapeutic range (TTR). Whether additional markers of HF severity are associated with TTR has not been investigated thoroughly. We aimed to examine the potential role of HF severity in the quality of warfarin control in patients with HF with reduced ejection fraction. Data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial were used to investigate the association between TTR and HF severity. Multivariable logistic regression models were used to examine the association of markers of HF severity, including New York Heart Association (NYHA) class, Minnesota Living with HF (MLWHF) score, and frequency of HF hospitalization, with TTR ≥70% (high TTR). We included 1,067 participants (high TTR, N = 413; low TTR, N = 654) in the analysis. In unadjusted analysis, patients with a high TTR were older and less likely to have had strokes or receive other antiplatelet agents. Those patients also had lower NYHA class, better MLWHF scores, greater 6-minute walk distance, and lower frequency of HF hospitalizations. Multivariable analysis showed that NYHA class III and/or IV (Odds ratio [OR] 0.68 [95% confidence intervals [CIs] 0.49 to 0.94]), each 10-point increase in MLWHF score (i.e., worse health-related quality of life) (OR 0.92 [0.86 to 0.99]), and higher number of HF hospitalization per year (OR0.45 [0.30 to 0.67]) were associated with decreased likelihood of having high TTR. In HF patients with systolic dysfunction, NYHA class III and/or IV, poor health-related quality of life, and a higher rate of HF hospitalization were independently associated with suboptimal quality of warfarin anticoagulation control. These results affirm the need to assess the new approaches, such as direct oral anticoagulants, to prevent thromboembolism in this patient population.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Severity of Illness Index; Stroke Volume; Thromboembolism; Treatment Outcome; Warfarin

Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with <60% of international normalized ratio (INR) measurements in the therapeutic range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure.. Patients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention.. The patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P <.0001). The intervention resulted in a significant improvement in the interventional group before versus after intervention (53% vs 80%, P <.0001) but not in the control group (45% vs 44%, P = .95). The percentage of patients with a TTR ≥60%, considered therapeutic, was substantially higher in the interventional group: 79% versus 25% (P <.0001). The INR variability (standard deviation of each patient's INR measurements) decreased significantly in the interventional group, from 0.53 to 0.32 (P <.0001) after intervention but not in the control group.. Patient-specific tailored intervention significantly improves anticoagulation therapy in patients with heart failure.

Topics: Aged; Anticoagulants; Comorbidity; Drug Monitoring; Female; Heart Failure; Humans; International Normalized Ratio; Israel; Linear Models; Male; Precision Medicine; Time Factors; Warfarin

The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).. Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue.. We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events).. After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates.. Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938).

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Stroke Volume; Warfarin

Heart failure (HF) patients have a high incidence of new-onset AF. Given the adverse prognostic influence of AF in HF, identifying patients at high risk of developing AF is important.. The incidence and factors associated with new-onset AF were investigated in patients in sinus rhythm with reduced LVEF enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Analyses involved clinical factors alone (n=2,219), and clinical plus echocardiographic findings (n=1,125). During 3.5±1.8 years of follow-up, 212 patients (9.6% of total cohort) developed AF. In both samples, new-onset AF was associated with age, male sex, White race, and IHD. Among echocardiographic variables, only LAD predicted AF. On multivariate Cox modeling, age (HR, 1.02; 95% CI: 1.00-1.03, P=0.008), IHD (HR, 1.37; 95% CI: 1.02-1.84, P=0.036) and LAD (HR, 1.48; 95% CI: 1.15-1.91, P=0.003) remained associated with AF onset. Patients with IHD, LAD>4.5 cm and age>50 years had a 2.5-fold higher risk of AF than patients without any of these characteristics (HR, 2.52; 95% CI: 1.72-3.69, P<0.0001).. Age, IHD and LAD independently predict new-onset AF in HF patients in sinus rhythm, at younger age and smaller LAD than generally believed. This information may be useful to risk-stratify HF patients for AF development, allowing close monitoring and possibly early detection. (Circ J 2016; 80: 619-626).

Topics: Age Factors; Aged; Aspirin; Atrial Fibrillation; Echocardiography; Follow-Up Studies; Heart Failure; Humans; Middle Aged; Stroke Volume; Warfarin

In the ENGAGE AF-TIMI 48 trial, edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding. The higher-dose edoxaban regimen (HDER; 60 mg dose-reduced to 30 mg once daily) has been approved in various countries in Europe, the USA, and Japan. Among patients treated with vitamin K antagonists (VKAs), symptomatic heart failure (HF) is an independent risk factor for lower time-in-therapeutic range, which reduces the efficacy and safety of VKA therapy. We evaluated the efficacy and safety of edoxaban compared with warfarin across the spectrum of HF severity in the ENGAGE AF-TIMI 48 trial.. Of 14 071 patients randomized to well-controlled warfarin or the HDER, 5926 (42%) had no history of HF, 6344 (45%) were in New York Heart Association (NYHA) class I-II, and 1801 (13%) were in NYHA class III-IV. The efficacy of edoxaban compared with warfarin in preventing stroke/SEE was similar in patients without and with HF regardless of the severity of HF; [HDER vs. warfarin: No-HF: hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.69-1.11; NYHA class I-II: HR 0.88, 95% CI 0.69-1.12; NYHA class III-IV: HR 0.83, 95% CI 0.55-1.25; Pinteraction = 0.97]. Compared with warfarin, HDER was consistently associated with lower risk of major bleeding (No-HF: HR 0.82, 95% CI 0.68-0.99; NYHA class I-II: HR 0.79, 95% CI 0.65-0.96; NYHA class III-IV: HR 0.79, 95% CI 0.54-1.17; Pinteraction = 0.96).. The relative efficacy and safety of HDER compared with well-managed warfarin in AF patients with HF were similar to those without HF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Pyridines; Stroke; Thiazoles; Treatment Outcome; Warfarin

The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin.. We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P<0.001), death alone (adjusted P=0.001), and improved net clinical benefit (adjusted P<0.001). A similar trend was observed for the other 2 outcomes, but significance was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for major hemorrhage).. In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Topics: Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Chi-Square Distribution; Double-Blind Method; Drug Monitoring; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Stroke; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Warfarin

We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin.

Topics: Aged; Anticoagulants; Aspirin; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Assessment; Stroke; Stroke Volume; Ventricular Dysfunction, Left; Warfarin

WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤ 35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified.. We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100 PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value.. Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100 PY) was greater than patients without (0.89/100 PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) <15% and 70 of 2,079 (3.4%) with EF ≥ 15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF <15% vs. ≥ 15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100 PY in patients with EF <15% and 0.95/100 PY in patients with EF ≥ 15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100 PY with EF <15% decreasing to 2.62/100 PY with EF <30%.. In a WARCEF exploratory analysis, prior stroke and EF <15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF.

Topics: Aged; Anticoagulants; Aspirin; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Recurrence; Stroke; Stroke Volume; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Cohort Studies; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Stroke Volume; Surveys and Questionnaires; Warfarin

In Rivaroxaban Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), rivaroxaban was noninferior to warfarin for the prevention of stroke and systemic embolic events and significantly reduced intracranial bleeding in patients with nonvalvular atrial fibrillation. We explore the safety and efficacy of rivaroxaban in patients with heart failure (HF).. A total of 9033 (63.7%) patients had HF. The primary efficacy analysis was rates of stroke or systemic embolism (per 100 patient-years) by intention to treat. The safety outcomes were major or nonmajor clinically relevant bleeding and hemorrhagic stroke during treatment. Patients with HF were younger (72 versus 74 years), more likely to have persistent atrial fibrillation (83.0% versus 77.6%), and had higher mean CHADS2 scores (3.7 versus 3.1). The efficacy of rivaroxaban compared with warfarin was similar in patients with HF (1.90 versus 2.09) and without HF (2.10 versus 2.54; P-interaction=0.62). The risk of major or nonmajor clinically relevant bleeding with rivaroxaban was similar to warfarin in patients with HF (14.22 versus 14.02) and without HF (16.12 versus 15.35; P-interaction=0.99). A reduction in hemorrhagic stroke was observed with rivaroxaban in patients with HF as in the overall trial (adjusted hazard ratio, 0.38; 95% confidence interval, 0.19-0.76; P-interaction=0.067). Among patients with HF, the efficacy of rivaroxaban was similar, irrespective of ejection fraction <40 or ≥ 40% (P-interaction=0.38), New York Heart Association class I-II versus III-IV (P-interaction=0.68), HF preserved or reduced ejection fraction (P-interaction=0.35), or CHADS2 score 2 versus ≥ 3 (P-interaction=0.48).. Treatment-related outcomes were similar in patients with and without HF and across HF subgroups. These findings support the use of rivaroxaban as an alternative to warfarin in patients with atrial fibrillation and HF. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Heart Failure; Humans; Intention to Treat Analysis; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Warfarin

We evaluated the effects of dabigatran compared with warfarin in the subgroup of patients with previous symptomatic heart failure (HF) in the RE-LY trial.. RE-LY compared two fixed and blinded doses of dabigatran (110 and 150 mg twice daily) with open-label warfarin in 18 113 patients with AF at increased risk for stroke. Among 4904 patients with HF, annual rates of stroke or systemic embolism (SE) were 1.92% for patients on warfarin compared with 1.90% for dabigatran 110 mg [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.69-1.42] and 1.44% for dabigatran 150 mg (HR 0.75, 95% CI 0.51-1.10). Annual rates of major bleeding were 3.90% for the group on warfarin, compared with 3.26% for dabigatran 110 mg (HR 0.83, 95% CI 0.64-1.09) and 3.10% for dabigatran 150 mg (HR 0.79, 95% CI 0.60-1.03). Rates of intracranial bleeding were significantly lower for both dabigatran dosages compared with warfarin in patients with HF (dabigatran 110 mg vs. warfarin, HR 0.34, 95% CI 0.14-0.80; dabigatran 150 mg vs. warfarin, HR 0.39, 95% CI 0.17-0.89). The relative effects of dabigatran vs. warfarin on the occurrence of stroke or SE and major bleeding were consistent among those with and without HF and those with low (≤40%) or preserved (>40%) LVEF (P interaction not significant).. The overall benefits of dabigatran for stroke/SE prevention, and major and intracranial bleeding, relative to warfarin in the RE-LY trial were consistent in patients with and without HF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; Warfarin

The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin.. We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03).. In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients ≥60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included.

Topics: Adult; Age Factors; Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stroke; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Warfarin

It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.. We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause.. The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82).. Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.).

Topics: Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk; Stroke; Stroke Volume; Treatment Outcome; 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

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

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

It is unknown if physician education through heart failure (HF) patient-specific quality-of-care report cards (HFRC) impacts outpatient HF guideline adherence.. A prospective pre-post design study was performed to test the hypothesis that a one-time, patient-specific HFRC delivered to physicians after HF patient (ejection fraction < or = 40%) discharge would lead to improved HF guideline adherence compared with control practitioners. Patients were contacted at 1, 3, and 6 months after discharge to assess medication usage and intolerances. Six month quality score (QS) was the primary end point, calculated as the sum of adherence to 4 medication performance measures (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, aldosterone inhibitors, and warfarin for atrial fibrillation).. The mean QS at discharge was 3.10 +/- 0.78 in controls (n = 189) and 3.25 +/- 0.79 in the HFRC group (n = 76, P = .11). Controlling for discharge QS, the HFRC resulted in a significantly improved QS at 3 months (beta = .11, P = .023) but not at the 6-month primary end point (beta = .084, P = .14). Controlling for baseline medication use, patients of practitioners receiving the HFRC were 32.5 (P = .019) and 8.5 (P = .030) times more likely to receive, or have a documented contraindication to, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker at 3 and 6 months, respectively. There were no significant differences in indicated beta-blocker, aldosterone inhibitor, or warfarin prescriptions at any follow-up.. Although one-time patient-specific report cards result in short-term statistically significant improvements in outpatient evidence-based HF care, the gain does not translate into sustained improvements in quality of care.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiology; Drug Utilization Review; Family Practice; Female; Follow-Up Studies; Guideline Adherence; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Practice Guidelines as Topic; Quality Indicators, Health Care; Warfarin

To examine further the relations of plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation) concentrations to the presence and onset of clinical congestive heart failure (CHF) and the degree of left ventricular (LV) dysfunction in patients taking part in the SPAF (stroke prevention in atrial fibrillation) study.. Plasma concentrations of vWf and sP-sel were measured by enzyme linked immunosorbent assay (ELISA) in 1321 participants in the SPAF III study and related to the presence and onset of clinical CHF, as well as echocardiographic findings. Of the 1321 patients with atrial fibrillation (AF), 331 (25%) had a documented history of clinical heart failure, of which 168 cases were related to a new or recurrent episode of acute decompensated heart failure occurring within the preceding three months.. Mean plasma vWf was higher among patients with AF and CHF (154 (29) v 144 (31) IU/dl, p < 0.001), particularly those with acute or recent decompensated symptoms. Patients with severe LV dysfunction on two dimensional echocardiography and low fractional shortening also had significantly higher vWf concentrations than those with no LV dysfunction. CHF patients with clinical features--with (156 (28) IU/dl) and without (152 (31) IU/dl) LV dysfunction--also had higher mean vWf concentrations than patients with asymptomatic LV dysfunction (146 (31) IU/dl, p < 0.001). The presence of mitral regurgitation in CHF was associated with lower vWf concentrations. Plasma sP-sel concentrations were not affected by presence, onset, or severity of heart failure.. CHF may contribute to hypercoagulability and thrombotic risk in AF through increased endothelial damage and dysfunction. Patients with acute or recent decompensated features have the highest degree of endothelial damage and dysfunction. The presence of CHF clinical features was an important determinant of plasma vWf concentrations.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; P-Selectin; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ventricular Dysfunction, Left; von Willebrand Factor; Warfarin

Topics: Anticoagulants; Aspirin; Clinical Trials Data Monitoring Committees; Clopidogrel; Heart Failure; Humans; Platelet Aggregation Inhibitors; Research Design; Research Support as Topic; Ticlopidine; Warfarin

The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and results The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions < or =35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization.. Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.

Topics: Adult; Aged; Anticoagulants; Aspirin; Clopidogrel; Embolism; Female; Heart Failure; Humans; Male; Middle Aged; Patient Selection; Platelet Aggregation Inhibitors; Prospective Studies; Research Design; Ticlopidine; Warfarin

The American College of Cardiology provided much useful new information to inform those who care for patients with heart failure about what they should and should not adopt into current clinical practice. The EPHESUS trial suggests a much wider role for aldosterone antagonists for the management of heart failure and left ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer, simpler warfarin substitute soon. ASCOT reinforces the potential futility of statin therapy unless it is well targeted. The results of the COMPANION study investigating cardiac resynchronisation devices and implantable defibrillators were encouraging but inconclusive and/or hard to interpret. UK-PACE again questions the use of dual chamber pacing. T-wave alternans is an interesting experimental technique that may be useful in selecting which patients need an implantable defibrillator, although the technology needs testing in an appropriate patient population.

Topics: Anticoagulants; Cardiac Pacing, Artificial; Defibrillators, Implantable; Electrocardiography; Eplerenone; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Spironolactone; Ventricular Dysfunction, Left; Warfarin

Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.. To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.. The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.. A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.. All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.. Composite end point of time to death or first hospitalization for congestive heart failure.. One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.. For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Pacemaker, Artificial; Single-Blind Method; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Warfarin

It is uncertain whether anti-thrombotic treatment reduces the incidence of thrombo-embolism in patients with heart failure, so there is a need for a large scale controlled study to assess the effects of anti-thrombotic therapy in this setting. We report the design of a randomized controlled multicenter double blind trial examining the effects of aspirin, warfarin and placebo in patients with heart failure on the risk of thrombo-embolism. We planned to recruit 6000 patients with heart failure without contraindications to anticoagulants or antiplatelet agents and to follow them for a mean time of 2 years following randomization. The study was planned to determine the rate of thrombo-embolic and haemorrhagic events and death among patients randomized to aspirin, warfarin and placebo, stratified according to the presence or absence of underlying coronary disease. Ancillary studies parallel to the main study will attempt to identify clinical and echocardiographic risk factors for thrombo-embolism and will also examine whether hemostatic or neurohormonal mechanisms contribute to an increase in the risk of thrombo-embolism in patients with heart failure. We hoped that the results of the study would improve the clinical management and cost-effectiveness of treatment for patients with heart failure. However, the recruitment of patients proved more difficult than expected and a number of centers decided not to participate. To avoid a great delay it was decided by the principal investigators and submitted to the executive committee to terminate enrolment in this study when 300 patients had been enrolled, and accept that this is a pilot study.

Topics: Anticoagulants; Aspirin; Double-Blind Method; Fibrinolytic Agents; Heart Failure; Humans; Longitudinal Studies; Middle Aged; Thromboembolism; Warfarin

Athero-thrombotic events are common among patients with heart failure but there is no evidence that anti-thrombotic therapy is safe or effective in this clinical setting.. The WASH study is a prospective, randomised, open-label, blinded-end-point pilot study comparing the outcome of management without anti-thrombotic therapy compared to treatment with aspirin or warfarin in three parallel arms in patients with chronic heart failure due to left ventricular systolic dysfunction. The primary aim of the study is to assess the feasibility of conducting a large study in which one-third of patients would be randomised to no anti-thrombotic therapy. The principal secondary aim of the study is to compare the effects of treatment on the combined end-point of death, non-fatal myocardial infarction and non-fatal stroke.. 279 patients have been randomised and by study close there were 626 patient-years of follow-up. The majority of patients randomised had heart failure secondary to coronary artery disease. We expect to commence data analysis in early 1999 and report later in that year.. This pilot study demonstrated that it is technically feasible to conduct a study that included a no anti-thrombotic treatment arm but that recruitment to such a study would be slow and costly. A large trial comparing the effects of aspirin, warfarin and clopidogrel in three separate groups without a placebo arm is now intended.

Topics: Anticoagulants; Aspirin; Feasibility Studies; Fibrinolytic Agents; Heart Failure; Humans; Multicenter Studies as Topic; Patient Selection; Pilot Projects; Randomized Controlled Trials as Topic; Research Design; Warfarin

This paper describes a preliminary experiment-conducted jointly by 2 centers-of permanent left ventricular pacing using leads inserted by the transvenous route and through the coronary sinus into the cardiac veins of the left ventricle free wall. The aim was to obtain permanent biventricular pacing in a totally endocavitary configuration in patients with severe LV dysfunction and drug-refractory heart failure. Two types of leads were used: nonspecific unipolar leads at the beginning of the experiment, followed by leads specifically designed to be used in the coronary sinus in a second step. The electrode could be fitted in an adequate location in 35 of the 47 patients (75.4%), with a 1.15 +/- 0.7 V acute pacing threshold and 11.8 +/- 5.7 mV R wave amplitude. The success rate was significantly higher with the specific electrodes (81.8% vs 53.3%, p < 0.001). The pacing and sensing thresholds upon implantation were not influenced by the type of lead or by the localization of the cardiac vein that was catheterized (great cardiac vein, lateral vein, postero-lateral or posterior vein, mid cardiac vein). In contrast, the pacing threshold was significantly lower (0.8 +/- 0.2 vs 1.8 +/- 0.8 V; p = 0.002) and the R wave amplitude tended to be greater (13.1 +/- 4.5 mV vs 9.3 +/- 6.5 mV; p = 0.07) when the tip electrode could be inserted distally into the vein, by comparison with a proximal site near the ostium. At the end of follow-up (10.2 +/- 8.7 months), 34 out of the 35 leads were still fully functional, with a chronic pacing threshold of 1.8 +/- 0.7 V and a R wave amplitude of 10.7 +/- 6 mV. To conclude, permanent LV pacing via the transvenous route is possible in most patients, with excellent safety and long-term results.

Topics: Aged; Anticoagulants; Cardiac Pacing, Artificial; Coronary Vessels; Electrodes, Implanted; Feasibility Studies; Female; Follow-Up Studies; Heart Failure; Humans; Male; Pacemaker, Artificial; Time Factors; Ventricular Dysfunction, Left; Warfarin

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

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

Topics: Acute Disease; Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Clinical Trials as Topic; Electrocardiography; Female; Heart Block; Heart Failure; Hemorrhage; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Placebos; Prothrombin Time; Pulmonary Embolism; Sampling Studies; Sodium; Thrombosis; Warfarin

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

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m

Topics: Aged; Atrial Fibrillation; Heart Failure; Humans; Kidney; Male; Registries; Risk Factors; Warfarin

Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.. A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.. The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.. This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Diabetes Mellitus; Heart Failure; Humans; Retrospective Studies; Rivaroxaban; Stroke; Warfarin

Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Pressure; Critical Pathways; Embolism; Female; Heart Failure; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Warfarin

The use of anticoagulation is mandatory for prevention of prosthetic valve thrombosis (PVT) worldwide, regardless of the valve type or position in the heart. In case a thrombosis causes symptomatic dysfunction, treatment usually includes the use of thrombolytic therapy or surgery. We report a case of PVT involving a patient with a mechanical aortic valve which was treated entirely with the use of anticoagulation therapy (warfarin).. A 58-year-old man had an aortic valve replacement using a Carbomedics. Only a few cases of symptomatic, thrombotic mechanical aortic valve were entirely treated with anticoagulation only. Our patient is one such case who had resolution of symptoms and improvement on NYHA functional classification (IV to I).

Topics: Anticoagulants; Aortic Valve; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Thrombosis; Warfarin

The use of a left ventricular assist device (LVAD) in treating advanced heart failure has increased. However, data regarding medical treatment and adherence following LVAD implantation is sparse, particularly whether socioeconomic factors (cohabitation status, educational level, employment status, and income) and multimorbidity influence these aspects, which are known to impact adherence in heart failure patients. We performed a nationwide cohort study of 119 patients with LVAD implanted between January 1, 2006, and December 31, 2018, who were discharged alive with LVAD therapy. We linked individual-level data from clinical LVAD databases, the Scandiatransplant Database, and Danish medical and administrative registers. Medical treatment 90-day pre-LVAD and 720-day post-LVAD were assessed using descriptive statistics in 90-day intervals. Medication adherence (proportion of days covered ≥80%) was assessed 181- to 720-day post-LVAD. The proportions of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blockers (67.0%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90-day post-LVAD were higher than pre-LVAD and were stable during follow-up. Medication adherence ranged from 86.7% (aspirin) to 97.8% (warfarin). Socioeconomic factors and multimorbidity did not influence medical medication use and adherence. Among LVAD patients, medical treatment and adherence are at high levels, regardless of socioeconomic background and multimorbidity.

Topics: Aspirin; Cohort Studies; Denmark; Heart Failure; Heart-Assist Devices; Humans; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Aged; Aged, 80 and over; Amyloidosis; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiomyopathies; Dabigatran; Factor Xa Inhibitors; Female; Heart Failure; Humans; Male; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin

Topics: Anticoagulants; Fibrinolytic Agents; Heart Failure; Humans; Longitudinal Studies; Warfarin

Baloxavir marboxil (BM) is a novel drug with a cap-dependent endonuclease inhibitory action for influenza A or B; it is highly safe and requires just a single oral dose. Patients with severe heart failure use implantable ventricular assist device (iVAD) until transplantation, but they have an increased risk of thrombosis development. Their warfarin is administered based on point-of-care testing (POCT) with a strict control of prothrombin time-international normalized ratio (PT-INR).. Here, we report a case of a patient with iVAD whose PT-INR was significantly increased from the target range after BM administration. The patient was a 45-year-old man and transplanted with iVAD; warfarin treatment was started when his PT-INR target range was 3.0-3.5. At home, he frequently self-measured PT-INR by POCT and precisely controlled the warfarin dose. He had a fever, was diagnosed with influenza A and was administered BM 40 mg. Thereafter, his PT-INR continued to increase, reaching 4.8 on day 12 of BM administration, exceeding his target range; warfarin was skipped for 1 day. In this case, based on the history of BM administration and clinical course, the increase in PT-INR could be due to BM. Considering the interaction between warfarin and BM, we suspected a possibility of competition for protein-binding sites. Increased PT-INR in the patient was detected early by POCT and thus severe bleeding was avoided.. Strict monitoring of PT-INR when using BM in patients taking warfarin is of clinical importance.

Topics: Anticoagulants; Dibenzothiepins; Heart Failure; Heart-Assist Devices; Humans; International Normalized Ratio; Male; Middle Aged; Morpholines; Prothrombin Time; Pyridones; Triazines; Warfarin

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

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

In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents.. A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity.. Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127-134.5); in vitro aspirin, 124 (114.5-137); and patients on dabigatran, 131 (130.5-135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5-143.5); in vitro low-dose apixaban, 141 (138.5-142); and patients on apixaban, 140 (138-142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137-150) versus 133.5 (128.5-140) minutes,. In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.

Topics: Anticoagulants; Blood Coagulation; Dabigatran; Heart Failure; Heart-Assist Devices; Hemolysis; Humans; Platelet Aggregation Inhibitors; Thrombosis; Warfarin

Topics: Administration, Oral; Antifibrinolytic Agents; Antithrombins; Atrial Fibrillation; Consensus; Delphi Technique; Diabetes Complications; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vascular Diseases; Warfarin

Antithrombotic therapy is administered after left ventricular assist device (LVAD) implantation to prevent thromboembolic events. Intracranial hemorrhage (ICH) is a life-threatening adverse event requiring immediate discontinuation of antithrombotics. We investigated the timing of antithrombotic resumption after ICH in patients with LVADs and the association between timing and risk of recurrent hemorrhage and thrombotic events.. We performed a multicenter, retrospective analysis of patients with ICH occurrence during LVAD antithrombotic regimen with subsequent resumption of antithrombotics from January 1, 2010, to December 31, 2017. Covariates included age, international normalized ratio, antithrombotic dosing, timing of resumption, modified Rankin score, and subsequent hemorrhagic and thrombotic events within 1 year post-ICH. Patients who did not resume anticoagulation were excluded.. Of 673 patients with LVADs, 85 (12.6%) developed ICH while being treated with antithrombotics. Forty-three were excluded due to death prior to resumption and one due to lack of resumption. The remaining 41 patients were on antithrombotics with a median (interquartile range [IQR]) international normalized ratio at ICH onset of 2.6 (1.8-3.6). Aspirin and warfarin were resumed at a median (IQR) of 5.5 (1.3-8.8) and 6.5 (4.0-15.5) days post-ICH, respectively. A continuous unfractionated heparin infusion was initiated in 16 (39.0%) patients at a median (IQR) of 2.5 (1.0-7.8) days post-ICH. During the 1-year follow-up after anticoagulation resumption, 11 (26.8%) patients suffered secondary hemorrhages and two (4.9%) suffered secondary thrombotic events. Using Kaplan-Meier method and log-rank test, we compared all patients who resumed anticoagulation by 6 days post-ICH to those who resumed after 6 days. There was no difference in freedom from secondary hemorrhagic event between the two groups (P = 0.75).. Despite timing of resumption of antithrombotic therapy after ICH, recurrent hemorrhagic events can be expected in one-quarter of these patients over the subsequent year.

Topics: Aged; Anticoagulants; Aspirin; Deprescriptions; Female; Fibrinolytic Agents; Heart Failure; Heart-Assist Devices; Heparin; Humans; International Normalized Ratio; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Thromboembolism; Time Factors; Warfarin

Warfarin is an anticoagulant prescribed in the treatment and prevention of thrombosis. Variation in dose requirements is different for everyone, and genetic factors have an effect on dose variation. Polymorphism of vitamin K epoxide reductase complex 1 (VKORC1) gene is identified as the main genetic factor involved in warfarin dosage requirement variations. This study aims to determine the frequency of VKORC1 polymorphism in patients using warfarin from Kerman city and investigated association between VKORC1 gene polymorphism and patient characteristics with warfarin dose requirement. A total of 112 patients taking warfarin with stable dose requirements enrolled in the study. DNA samples from these patients were genotyped for VKORC1 gene polymorphism by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP) and examined associations between demographic characteristics (e.g. age, sex, smoking, etc.) and genetic factors with maintenance dose of warfarin. The most common genotype was VKORC1 GA (48.2%). genotype frequency subjects carried VKORC1 GG and AA were 39.3% and 12.5%, respectively. In addition, a significant relationship was found between VKORC1-1639G>A and the daily dose of warfarin (P = 0.011, R

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Female; Genetic Association Studies; Heart Failure; Humans; Iran; Male; Middle Aged; Polymorphism, Genetic; Vitamin K Epoxide Reductases; Warfarin; Young Adult

Treatment and prognosis of elderly patients with atrial fibrillation (AF) may differ by the experience of fall or bone fracture. However, their current status is still unclear. From our institute database between 2010 and 2015, 674 AF patients with age ≥ 70 years were selected and were divided into those who experienced fall or fracture during the observation period (F/F group; n = 49) and those who did not (non-F/F group; n = 625). We compared the treatment and prognosis between the 2 groups. Patients in the F/F group were older (79 vs 76 years, P < 0.001) and had more comorbidities compared with those in the non-F/F group. The prescription rate of oral anticoagulant was similar between the two groups (77.6% vs 68.2%, P = 0.201), where warfarin was predominant. The F/F group was not associated with higher incidence of ischemic stroke. The F/F group was associated with a higher incidence of heart failure events (adjusted odds ratio (OR) 3.88; 95% confidence intervals (Cl) 1.70-8.85; P = 0.001), and cardiovascular events (OR 3.43; 95% Cl 1.71-6.85; P < 0.001). In elderly AF patients in a cardiovascular hospital, the experience of fall or fracture did not affect the prescription of oral anticoagulants and the incidence of ischemic stroke, but it was significantly associated with increase of heart failure.

Topics: Accidental Falls; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Female; Fractures, Bone; Heart Disease Risk Factors; Heart Failure; Humans; Incidence; Japan; Male; Risk Assessment; Stroke; Warfarin

Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study.. In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction ≥50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate ≥50 beats per minute, an estimated glomerular filtration rate ≥30 mL/min/1.73 m. Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes.. Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiotonic Agents; Cause of Death; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mineralocorticoid Receptor Antagonists; Mortality; Patient Readmission; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Warfarin

Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure.. This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy.. Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Topics: Factor Xa Inhibitors; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs.. Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy.. After the first measurement of FMD, 18 patients "switched" to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin. "Switched" patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p < 0.0001); C-reactive protein (CRP) levels decreased in "switched" patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p < 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = -0.50, p < 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p < 0.05).. Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Stroke; Warfarin

Topics: Anticoagulants; Female; Follow-Up Studies; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Prosthesis Design; Retrospective Studies; Thrombosis; Time Factors; Warfarin

Left ventricular assist devices (LVADs) are used to treat patients with severe (New York Heart Association class IV) heart failure. Thrombosis and bleeding are severe LVAD-related complications; thus, an effective anticoagulation regimen is crucial for successful postoperative management. The CH-VAD™ (CH Biomedical, Inc.) is a small, implantable, full-support (>5 L/min) LVAD with a centrifugal flow pump that has a fully magnetically levitated rotor, which confers superior hemocompatibility. In this study, the CH-VAD™ was implanted in two calves to evaluate its hemocompatibility and to establish an anticoagulation regimen for future GLP (good laboratory practice) studies. Heparin infusion was used during the surgery, and during postoperative management, the proper dosage of warfarin was given orally to maintain an international normalized ratio (INR) between 2.0 and 3.0. Pump performance, animal condition, and hematology results were recorded throughout the study (approximately 60 days). The results show that under the established anticoagulation regimen, the CH-VAD™ was well tolerated in the bovine model, with no significant thrombus or thromboembolic lesion formation in distal end organs. Low plasma free hemoglobin levels suggest that the device did not cause hemolysis. These results and the experience gained pave the way for future GLP studies.

Topics: Animals; Cattle; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Thrombosis; Warfarin

The use of warfarin and aspirin in combination is restricted to limited patients under relevant guidelines.. To evaluate the prevalence of the inappropriate combination of aspirin and warfarin therapy in daily practice and its risks.. Cross-sectional study.. The awareness, efficacy, safety, and time in the therapeutic range of warfarin in the Turkish population study is a multi-center observational study that includes 4987 patients using warfarin for any reason between January 1, 2014, and December 31, 2014. To determine the prevalence of inappropriate combination use in daily practice, all patients who had a history of atherosclerotic disease (ischemic heart disease, peripheral artery disease) or cerebrovascular disease (n=1498) were excluded. The data of 3489 patients were analyzed. We defined inappropriate combination as all patients who received aspirin and warfarin regardless of the indication for warfarin use, under the direction of the European Society of Cardiology guideline recommendation.. The mean age of patients was 59.2±13.8 years (41.8% male). The prevalence of the inappropriate use of warfarin and aspirin combination was 20.0%. The prevalence of combination therapy in patients with a primary indication for mechanical heart valve, non-valvular atrial fibrillation, and other reasons was 20.5%, 18.7%, and 21.0%, respectively. Multivariate logistic regression analysis revealed that age (odds ratio, 1.009; 95% confidence interval, 1.002-1.015; p=0.010), heart failure (odds ratio, 1.765; 95% confidence interval, 1.448-2.151; p<0.001), smoking (odds ratio, 1.762; 95% confidence interval, 1.441-1.153; p<0.010), chronic kidney disease (odds ratio, 2.057; 95% confidence interval, 1.494-2.833; p<0.001), and deep vein thrombosis (odds ratio, 0.463; 95% confidence interval, 0.229-0.718; p=0.001) were independent predictors of combination therapy (r2=0.66). The mean time in therapeutic range of patients receiving combination therapy was significantly lower than in those on warfarin monotherapy (51.6±27.05 vs. 54.7±23.93; p=0.006). Overall, 19.4% (n=677) of patients had a bleeding event (major bleeding 13.0%, n=88) within a year. Percentages of patients with combination therapy were significantly higher in patients with major bleeding than in patients without major bleeding (29.5% vs. 19.7%; p=0.023).. Our study demonstrated that 20.0% of patients taking warfarin use concomitant aspirin inappropriately in daily practice. Patients receiving aspirin with warfarin were demonstrated to have more comorbidities, lower time in therapeutic range levels, and higher bleeding rates.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cross-Sectional Studies; Drug Combinations; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Prevalence; Statistics, Nonparametric; Treatment Outcome; Turkey; Warfarin

This study aimed to assess the risk of procedure-related complications of percutaneous epicardial access (EpiAcc) for radiofrequency catheter ablation (RFA) of ventricular arrhythmias (VAs) in patients chronically treated oral anticoagulants (OACs) with warfarin compared to those not on OACs.. We analyzed 205 patients (53 ± 16 years, 155 males) undergoing percutaneous EpiAcc as part of an RFA for VAs, and compared the outcome between patients chronically on OACs with warfarin (OAC group) and those without (non-OAC group).. Forty-seven patients (23%) were chronically treated on OACs before their procedure. EpiAcc in patients on OAC (OAC group) was not associated with an increased risk of cardiac tamponade (11% vs. 6%, p = 0.238) compared to non-OAC group, but a higher risk of need for blood transfusion (17% vs. 6%; p = 0.013). With respect to the OAC group, the international normalized ratio (INR) on the day of the RFA was ≥ 2.0 in 9 patients (19%) and < 2.0 in the remaining 38 patients (81%). The rate of all complication and blood transfusion were similar between them (11% vs. 21%; p = 0.496, 11% vs. 18%; p = 0.600).. Percutaneous EpiAcc in patients on chronic OAC with warfarin did not significantly increase the risk of cardiac tamponade, but was associated with a higher risk of need for blood transfusion. EpiACC in patients with an INR > 2.0 is reasonable in experienced hands when clinical indications are strong.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Anticoagulants; Cardiac Tamponade; Catheter Ablation; Cohort Studies; Epicardial Mapping; Feasibility Studies; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Postoperative Complications; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Survival Rate; Tachycardia, Ventricular; Treatment Outcome; Warfarin

Heart failure (HF) is a common co-morbidity in non-valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time-in-therapeutic range with warfarin. We assessed the real-world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co-morbid HF.. Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co-morbid HF treated in routine practice. The general consistency between this real-world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Heart Failure; Humans; Incidence; Male; Medicare; Propensity Score; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Anticoagulation therapy with warfarin is common before heart transplantation and complicates perioperative management.. This single-center, noninterventional, retrospective cohort study evaluated heart transplant patients before and after institution of a prothrombin complex concentrates-based preoperative warfarin reversal protocol for heart transplantation. Patients with international normalized ratio (INR) greater than 1.5 who received prothrombin complex concentrate (PCC) before heart transplant surgery were compared with a control group before implementation of a PCC protocol. Coprimary endpoints were utilization of individual blood products. Secondary endpoints included in-hospital mortality, reoperation for bleeding, delayed sternal closure, thromboembolic events, duration of chest tube use, time to extubation, intensive care unit length of stay, and hospital length of stay.. The study included 106 consecutive heart transplant patients (PCC cohort = 57, historical control cohort = 49). There was a significant reduction in fresh frozen plasma utilization in the PCC cohort (6 units versus 8 units, p = 0.002). Rates of packed red blood cells and platelet transfusion were similar between groups. There was a significant increase in the incidence of cryoprecipitate utilization in the PCC cohort, which can likely be attributed to decreased antifibrinolytic utilization. There were no differences in secondary endpoints between groups, including thromboembolic events.. This study found that a PCC-based warfarin reversal protocol significantly reduced fresh frozen plasma utilization compared with historical controls without affecting other clinically important surgical outcomes. These data suggest that PCC is a valuable tool for INR normalization that could safely reduce fresh frozen plasma administration and offer a practical alternative to traditional approaches for INR reversal before heart transplantation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Blood Transfusion; Clinical Protocols; Female; Heart Failure; Heart Transplantation; Humans; International Normalized Ratio; Length of Stay; Male; Middle Aged; Plasma; Postoperative Complications; Retrospective Studies; Warfarin; Young Adult

Large artery stiffening contributes to the pathophysiology of heart failure (HF) and associated comorbidities. MGP (matrix Gla-protein) is a potent inhibitor of vascular calcification. MGP activation is vitamin K-dependent. We aimed (1) to compare dp-ucMGP (dephospho-uncarboxylated MGP) levels between subjects with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) and subjects without HF; (2) to assess the relationship between dp-ucMGP levels and arterial stiffness; and (3) to assess the relationship between warfarin use, dp-ucMGP levels, and arterial stiffness in HF. We enrolled 348 subjects with HFpEF (n=96), HFrEF (n=53), or no HF (n=199). Carotid-femoral pulse wave velocity, a measure of large artery stiffness, was measured with arterial tonometry. Dp-ucMGP was measured with ELISA. Dp-ucMGP levels were greater in both HFrEF (582 pmol/L; 95% CI, 444-721 pmol/L) and HFpEF (549 pmol/L; 95% CI, 455-643 pmol/L) compared with controls (426 pmol/L; 95% CI, 377-475 pmol/L; ANCOVA P=0.0067). Levels of dp-ucMGP were positively associated with carotid-femoral pulse wave velocity (standardized β, 0.31; 95% CI, 0.19-0.42; P<0.0001), which was also true in analyses restricted to patients with HF (standardized β, 0.34; 95% CI, 0.16-0.52; P=0.0002). Warfarin use was significantly associated with carotid-femoral pulse wave velocity (standardized β, 0.13; 95% CI, 0.004-0.26; P=0.043), but this relationship was eliminated after adjustment for dp-ucMGP. In conclusion, levels of dp-ucMGP are increased in HFpEF and HFrEF and are independently associated with arterial stiffness. Future studies should investigate whether vitamin K supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffness in HFpEF and HFrEF.

Topics: Aged; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Heart Failure; Humans; Male; Matrix Gla Protein; Middle Aged; Prospective Studies; Pulse Wave Analysis; Stroke Volume; Vascular Stiffness; Vitamin K; Warfarin

Although novel oral-anticoagulants are widely used in patients with atrial fibrillation (AF) for stroke prevention, there was only limited evidence for their use in left ventricular (LV) thrombus.. A 41-year-old man who presented with acute onset of right-hand clumsiness and aphasia even under high international normalized ratio (INR: 7.64) from warfarin use. He was previously treated with warfarin for the LV thrombus and non-valvular AF. Brain magnetic resonance imaging (MRI) showed multiple acute infarction in the cortex of the bilateral frontal lobes, left parietal lobe, and bilateral central semiovale, which highly suggested embolic stroke.. The repeated transthoracic echocardiogram still revealed LV thrombus (1.27 × 0.90 cm), which failed to respond to warfarin therapy.. Due to acute infarctions occurred under supratherapeutic range of INR, we switched warfarin to edoxaban (dose: 60 mg/day) after INR decreased to less than 2.. The thrombus disappeared after receiving edoxaban for 23 days, and no more recurrent stroke was noted for more than 6 months.. This is the first case demonstrates that while facing ineffective treatment of warfarin for LV thrombus, edoxaban could be safely and effectively used under this situation.

Topics: Adult; Anticoagulants; Brain Ischemia; Heart Failure; Heart Ventricles; Humans; Male; Pyridines; Retreatment; Stroke; Thiazoles; Thrombosis; Warfarin

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

Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48-0.85), MB (hazard ratio = 0.66, 0.58-0.76), and MACE (hazard ratio = 0.73,0.67-0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77-0.99; hazard ratio = 0.84, 0.79-0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52-0.81) and higher MB rate (hazard ratio = 1.18, 1.08-1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57-0.89; hazard ratio = 0.55, 0.49-0.63) and MACE rates (hazard ratio = 0.80, 0.69-0.93; hazard ratio = 0.86, 0.79-0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Heart Failure; Humans; Incidence; Kaplan-Meier Estimate; Male; Medicare; Patient Safety; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Risk; Rivaroxaban; Treatment Outcome; United States; Warfarin

The aim of this study was to investigate the factors associated with low health-related quality of life (HRQoL) compared between younger and older Thai patients with non-valvular atrial fibrillation (NVAF).. This is a cross-sectional analysis of baseline data from a prospective NVAF registry from 24 hospitals located across Thailand. Patient demographic, clinical, lifestyle, and medication data were collected at baseline. EuroQOL/EQ-5D-3L was used to assess HRQoL. Health utility was calculated for the entire study population, and low HRQoL was defined as the lowest quartile. Multivariate logistic regression was used to identify factors that significantly predict low HRQoL among younger and older (≥ 65 years) patients with NVAF.. Among the 3218 participants that were enrolled, 61.0% were aged older than 65 years. Mean HRQoL was lower in older than in younger patients (0.72 ± 0.26 vs. 0.84 ± 0.20; p < 0.001). Factors associated with low HRQoL among younger NVAF patients were the treatment-related factors bleeding history (p = 0.006) and taking warfarin (p = 0.001). Among older patients, the NVAF-related complications ischemic stroke or TIA, heart failure (HF), and dementia (all p < 0.001) were all significantly associated with low HRQoL. Dementia is the factor that most adversely influences low HRQoL among older NVAF. Interestingly, symptomatic NVAF was found to be a protective factor for low HRQoL (p < 0.001).. Bleeding history and taking warfarin among younger patients, and ischemic stroke/TIA, HF, and dementia among older patients are significant predictors of low HRQoL. These factors should be taken into consideration when selecting treatment options for patients with NVAF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Dementia; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Registries; Stroke; Thailand; Warfarin

Topics: Atrial Fibrillation; Body Mass Index; Heart Failure; Humans; Obesity; Pyridines; Thiazoles; Warfarin

In patients with left ventricular assist device support and aspirin allergy, the choice of effective antiplatelet strategy remains a challenge. We compared the antithrombotic effect of clopidogrel vs ticagrelor in an LVAD patient with aspirin allergy by using a modified protocol of the thrombin generation test, accounting selectively for the platelet contribution on thrombin generation. Our results demonstrate enhanced antithrombotic efficacy offered by ticagrelor. Consistent with experimental results, the patient has passed more than 300 days without thromboembolic complications. This study provides additional mechanistic rationale supporting clinical evidence and opens the perspective to identify individual poor responsiveness to drugs by specifically evaluating drug-mediated platelet function.

Topics: Aspirin; Clopidogrel; Drug Hypersensitivity; Drug Therapy, Combination; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Thrombosis; Ticlopidine; Warfarin

Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes.. A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression.. Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (β = -6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p = 0.01).. Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal.

Topics: Adult; Aged; Anticoagulants; Blood Banks; Blood Coagulation Factors; Blood Transfusion; Female; Health Care Costs; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Male; Middle Aged; Plasma; Procedures and Techniques Utilization; Retrospective Studies; Treatment Outcome; Warfarin

Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality.. Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses.. From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85).. Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.

Topics: Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Female; Heart Failure; Heart-Assist Devices; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Quality of Life; Retrospective Studies; Risk Factors; Stroke; Warfarin

The HeartMate 3 left ventricular assist system is engineered to avoid pump thrombosis, yet bleeding complications persist. We investigated the safety of low-intensity anti-coagulation in patients with the HeartMate 3.. The Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot study is a prospective, single-arm study of low-intensity warfarin anti-coagulation in patients implanted with the HeartMate 3 pump. After standard warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and aspirin for 6 weeks post-implant, patients were transitioned to a lower INR target range of 1.5 to 1.9. The primary end-point was a composite of survival free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or major bleeding (excluding peri-operative bleeding) with at least 6-month post-implant follow-up. Time in therapeutic range (TTR) was measured to assess anti-coagulation target efficacy using the Rosendaal method. A safety algorithm to monitor for signs of pump thrombosis was developed and implemented.. We enrolled 15 patients (mean age 57.3 ± 13.3 years), 13 men with advanced heart failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of bridge-to-transplant or destination therapy. The primary end-point was met in 14 of 15 (93 ± 6%) patients; 1 patient developed recurrent gastrointestinal bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months) was 75.3 ± 8.6%. No thrombotic events occurred.. This pilot study suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6-months post-implant. A large-scale trial is now warranted.

Topics: Adult; Aged; Anticoagulants; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Prosthesis Design; Warfarin

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

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

This study aimed to investigate relationships between times in therapeutic range (TTR) or warfarin sensitivity indexes (WSI) and VKORC1-1639G>A and CYP2C9 polymorphisms in patients with left ventricular assist devices (LVAD).. Severe heart failure patients who received LVAD from January 1, 2013 to October 31, 2017 were recruited. Relationships between TTR or WSI and VKORC1-1639G>A and CYP2C9 gene polymorphisms were investigated immediately after LVAD implantation (period 1) and immediately prior to hospital discharge (period 2).. Among 54 patients, 31 (72.1%) had VKORC1-1639AA and CYP2C9*1/*1 (AA group) polymorphisms and 12 (27.9%) had VKORC1-1639GA and CYP2C9*1/*1 (GA group) polymorphisms. During period 1, mean prothrombin time-international normalized ratio (PT-INR) values were significantly higher in the AA group than in the GA group (2.21 vs. 2.05, p < 0.0001). Mean WSI values were 1.68-fold greater in the AA group than in the GA group (1.14 vs. 0.68, p < 0.0001). In addition, times below the therapeutic range (TBTR) in the GA group were significantly greater than in the AA group during period 1 (39.8 vs. 28.3%, p = 0.032), and insufficient PT-INR was more frequent in the GA group than in the AA group. However, mean PT-INR values during period 2 did not differ and no significant differences in TTR, TATR, and TBTR values were identified. In subsequent multivariable logistic regression analyses, the VKORC1-1639GA allele was significantly associated with insufficient anticoagulation.. Patients with the VKORC1-1639GA and CYP2C9*1/*1 alleles may receive insufficient anticoagulation therapy during the early stages after implantation of LVAD, and VKORC1-1639G>A and CYP2C9 genotyping may contribute to more appropriate anticoagulant therapy after implantation of LVAD.

Topics: Adult; Anticoagulants; Asian People; Cytochrome P-450 CYP2C9; Female; Genotype; Heart Failure; Heart Ventricles; Heart-Assist Devices; Humans; Japan; Male; Middle Aged; Polymorphism, Genetic; Treatment Outcome; Vitamin K Epoxide Reductases; Warfarin

We describe a case with severe heart failure and moderate aortic stenosis. Due to previous atrial fibrillation and ischaemic heart disease, this patient was treated with both dabigatran and clopidogrel. Despite this, a large mural thrombus was found on echocardiography. The treatment was altered to warfarin, but the thrombus did not resolve during the next eight months.Guidelines for the use of anticoagulant treatment in left ventricular thrombus are needed. Previously, a few cases presenting resistance to novel oral anticoagulants have been published and cases with thrombus formation due to dabigatran have been described. Our patient showed resistance to both dabigatran and warfarin, and there was no thrombus resolution when changing the treatment to warfarin.

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Clopidogrel; Dabigatran; Diagnosis, Differential; Drug Therapy, Combination; Dyspnea; Echocardiography; Fatal Outcome; Heart Diseases; Heart Failure; Humans; Male; Thrombosis; Ticlopidine; Warfarin

A 20-year-old male affected by transfusion-dependent β-thalassemia (β-thal), was prescribed intensive chelation therapy with deferoxamine (DFO) and deferiprone (DFP) because of severe hepatic and cardiac iron overload and β-blocker and warfarin to manage a previous event of atrial fibrillation (AFib) and heart failure. After a few months, he developed critical liver failure, renal tubulopathy and severe electrolyte imbalance. Laboratory and instrumental evaluations were performed to carry out differential diagnosis of acute liver failure and an exclusion diagnosis of drug induced liver injury (DILI) was made. The cholestatic pattern suggested warfarin as the main causative agent and polypharmacy, liver iron overload and heart failure as aggravating factors. Warfarin is a drug commonly prescribed in thalassemia patients who often need polypharmacy for the management of anemia- and iron-related complications. Strict monitoring and multidisciplinary approaches are mandatory to avoid preventable mortality in this fragile population.

Topics: Adrenergic beta-Antagonists; beta-Thalassemia; Chelation Therapy; Chemical and Drug Induced Liver Injury; Critical Illness; Deferiprone; Heart Failure; Humans; Iron Overload; Male; Warfarin; Young Adult

Stroke prophylaxis in patients with atrial fibrillation (AF) and heart failure (HF) in the era of direct oral anticoagulants is not well characterized. Using data from American Heart Association Get With The Guidelines-AFIB, we sought to evaluate oral anticoagulation (OAC) use at discharge among AF patients with concomitant HF.. AF patients with a diagnosis of HF hospitalized from January 2013 to March 2017 were included. We compared patient characteristics and use of OAC at discharge among patients with reduced (redundant ejection fraction [EF], EF≤40%), borderline (40%

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Humans; Patient Discharge; Practice Patterns, Physicians'; Risk Factors; Warfarin

Hypereosinophilic syndrome is a rare entity that can develop secondary to overproduction of eosinophilopoietic cytokines or as idiopathic disease. Cardiac involvement, which occurs often, is divided into 3 stages, the latter of which is nonreversible and leads to severe heart failure. Early detection and treatment of the syndrome is essential. For this reason, genetic testing for the FIP1L1-PDGFRA fusion gene has recently been added to the diagnostic algorithm. Patients with this mutation are at increased risk for the development of cardiac involvement and typically respond to treatment with the tyrosine kinase inhibitor imatinib mesylate.

Topics: Adult; Anticoagulants; Antineoplastic Agents; Bone Marrow Examination; Echocardiography; Heart Failure; Humans; Hypereosinophilic Syndrome; Imatinib Mesylate; Male; mRNA Cleavage and Polyadenylation Factors; Mutation; Oncogene Proteins, Fusion; Prednisone; Receptor, Platelet-Derived Growth Factor alpha; Thrombosis; Treatment Outcome; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Component Transfusion; Breast Neoplasms; Female; Heart Failure; Humans; International Normalized Ratio; Plasma; Pleural Effusion, Malignant; Preoperative Care; Stroke; Thoracentesis; Transfusion Reaction; Vitamin K; Warfarin

Pump thrombosis and hemolysis in patients with left ventricular assist devices (LVADs) are associated with significant morbidity and mortality. Intensification of anticoagulation has been suggested as potential therapy, with mixed results. The aim of this study is to assess the safety and efficacy of adding eptifibatide with or without an anticoagulation agent in managing patients with LVAD presenting with hemolysis and suspected pump thrombosis. This retrospective single center study included all patients who presented with their first episode of suspected pump thrombosis and were treated with eptifibatide with or without an anticoagulant between March 1, 2011 and July 30, 2015. A total of 27 patients (23 HeartMate II, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average lactate dehydrogenase on presentation was 1111 and 63% of patients had power elevations. The average international normalized ratio (INR) on admission was 2.4, with INR of ≥2 in 21/27 patients. All patients received eptifibatide: 10 received eptifibatide only, 9 received eptifibatide and argatroban, and 8 received eptifibatide and heparin. Warfarin was continued in 25/27 patients. Overall, 21 patients (77.8%) were successfully treated medically, 5 (18.5%) underwent pump exchange, and 1 (3.7%) died. There were no differences in outcomes or complications between the three treatment groups. Despite initial success, 12/21 patients developed repeat episodes of hemolysis at 1 year. The 1-year survival in the patients treated medically was 90% and surgically was 60%. Our experience indicates that medical therapy for hemolysis and suspected LVAD thrombosis with warfarin and eptifibatide alone or in combination with argatroban or heparin appears safe and may be effective, although the episodes of recurrent hemolysis after medical management remain high.

Topics: Adult; Aged; Anticoagulants; Arginine; Eptifibatide; Female; Heart Failure; Heart-Assist Devices; Hemolysis; Heparin; Humans; Male; Middle Aged; Peptides; Pipecolic Acids; Platelet Aggregation Inhibitors; Retrospective Studies; Sulfonamides; Thrombosis; Warfarin; Young Adult

Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6%) patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients) associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32-0.53). Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days) continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Incidence; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke; Warfarin

Sex-specific effectiveness of rivaroxaban (RIVA), dabigatran (DABI), and warfarin in reducing myocardial infarction (MI), heart failure (HF), and all-cause mortality among patients with atrial fibrillation are not known. We assessed sex-specific associations of RIVA, DABI, or warfarin use with the risk of MI, HF, and all-cause mortality among patients with atrial fibrillation.. Medicare beneficiaries (men: 65 734 [44.8%], women: 81 135 [55.2%]) with atrial fibrillation who initiated oral anticoagulants formed the study cohort. Inpatient admissions for MI, HF, and all-cause mortality were compared between the 3 drugs separately for men and women using 3-way propensity-matched samples. In men, RIVA use was associated with a reduced risk of MI admissions compared with warfarin use (hazard ratio [95% confidence interval (CI): 0.59 [0.38-0.91]), with a trend towards reduced risk compared with DABI use (0.67 [0.44-1.01]). In women, there were no significant differences in the risk of MI admissions across all 3 anticoagulants. In both sexes, RIVA use and DABI use were associated with reduced risk of HF admissions (men: RIVA; 0.75 [0.63-0.89], DABI; 0.81 [0.69-0.96]) (women: RIVA; 0.64 [0.56-0.74], DABI; 0.73 [0.63-0.83]) and all-cause mortality (men: RIVA; 0.66 [0.53-0.81], DABI; 0.75 [0.61-0.93]) (women: RIVA; 0.76 [0.63-0.91], DABI; 0.77 [0.64-0.93]) compared with warfarin use.. RIVA use and DABI use when compared with warfarin use was associated with a reduced risk of HF admissions and all-cause mortality in both sexes. However, reduced risk of MI admissions noted with RIVA use appears to be limited to men.

Topics: Administration, Oral; Administrative Claims, Healthcare; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Chi-Square Distribution; Dabigatran; Databases, Factual; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Medicare; Multivariate Analysis; Myocardial Infarction; Patient Admission; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Rivaroxaban; Sex Factors; Time Factors; Treatment Outcome; United States; Warfarin

The effect of non-vitamin K antagonist oral anticoagulants on left atrial appendage (LAA) thrombus has not been fully elucidated. There are a few reports showing resolution of LAA thrombus with apixaban. An 84-year-old woman was admitted to our hospital due to acute exacerbation of chronic heart failure and marked tachycardia with atrial fibrillation. She had permanent atrial fibrillation and was treated with warfarin; however, transthoracic echocardiography revealed a non-mobile thrombus in the LAA. Therefore, we switched warfarin to apixaban at a dose of 5 mg/day. After two weeks on that therapy, the thrombus in the LAA was successfully resolved.

Topics: Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Echocardiography; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Heart Failure; Humans; Pyrazoles; Pyridones; Thrombosis; Warfarin

We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy.. A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy.. Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis.. The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation.

Topics: Adult; Aged; Anticoagulants; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Middle Aged; Time Factors; Ventricular Dysfunction, Right; Warfarin

The purpose of this study was to elucidate the barriers and enablers to adherence to anticoagulation in individuals with chronic heart failure (CHF) with concomitant atrial fibrillation (AF) from the perspective of patients and providers.. CHF and AF commonly coexist and are associated with increased stroke risk and mortality. Oral anticoagulation significantly reduces stroke risk and improves outcomes. Yet, in approximately 30% of cases, anticoagulation is not commenced for a variety of reasons.. Qualitative study using narrative inquiry.. Data from face-to-face individual interviews with patients and information retrieved from healthcare file note review documented the clinician perspective. This study is a synthesis of the two data sources, obtained during patient clinical assessments as part of the Atrial Fibrillation And Stroke Thromboprophylaxis in hEart failuRe (AFASTER) Study.. Patient choice and preference were important factors in anticoagulation decisions, including treatment burden, unfavourable or intolerable side effects and patient refusal. Financial barriers included cost of travel, medication cost and reimbursement. Psychological factors included psychiatric illness, cognitive impairment and depression. Social barriers included homelessness and the absence of a caregiver or lack of caregiver assistance. Clinician reticence included fear of falls, frailty, age, fear of bleeding and the challenges of multimorbidity. Facilitators to successful prescription and adherence were caregiver support, reminders and routine, self-testing and the use of technology.. Many barriers remain to high-risk individuals being prescribed anticoagulation for stroke prevention. There are a number of enabling factors that facilitate prescription and optimise treatment adherence. Nurses should challenge these treatment barriers and seek enabling factors to optimise therapy.. Nurses can help patients and caregivers to understand complex anticoagulant risk-benefit information, and act as a patient advocate when making complex stroke prevention decisions.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Health Services Accessibility; Heart Failure; Humans; Male; Medication Adherence; Middle Aged; Patient Preference; Practice Patterns, Physicians'; Qualitative Research; Risk Assessment; Risk Factors; Stroke; Warfarin

The effect of warfarin on the risk of cardiovascular (CV) disease is unknown among chronic hemodialysis patients with atrial fibrillation (HD-AF).. Population-based propensity score and prescription time-distribution matched cohort study including 6719 HD-AF patients with CHA. Warfarin treatment in HD-AF patients with AF preceding HD was associated with higher risks of developing congestive heart failure [hazard ratio (HR)=1.82, 95% confidence interval (CI)=1.29-2.58, p<0.01], peripheral artery occlusive disease (HR=3.42, 95% CI=1.86-6.31, p<0.01), and aortic valve stenosis (HR=3.20, 95% CI=1.02-9.98, p<0.05). Warfarin users were not associated with risks of ischemic or hemorrhagic stroke and all-cause mortality as compared to nonusers.. Warfarin may be associated with vascular calcification, increasing the risks of congestive heart failure and peripheral artery occlusive disease among HD-AF patients.

Topics: Adult; Aged; Anticoagulants; Arterial Occlusive Diseases; Atrial Fibrillation; Brain Ischemia; Female; Heart Failure; Humans; Male; Middle Aged; Renal Dialysis; Stroke; Vascular Calcification; Warfarin

Warfarin is the most commonly used oral anticoagulant and is widely prescribed to prevent thromboembolic events. Warfarin-dependent spontaneous breast hematoma is a very rare complication. Presently described is rare case of warfarin-induced breast hematoma.

Topics: Anticoagulants; Breast; Female; Heart Failure; Hematoma; Humans; Middle Aged; Warfarin

Topics: Aged; Angiodysplasia; Blood Coagulation Tests; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Prosthesis Design; Pyrazoles; Pyridones; Risk Factors; Thrombosis; Treatment Outcome; Ventricular Function, Left; Warfarin

Hematologic adverse events are common during continuous flow left ventricular assist device support; yet, their relation to antiplatelet therapy, including aspirin (ASA) dosing, is uncertain.. A single-center retrospective review of all patients supported by a continuous flow left ventricular assist device (Heart Mate II) from June 2006 to November 2014 was conducted. Patients were categorized into 3 groups: (1) ASA 81 mg+dipyridamole 75 mg daily (n = 26) with a target international normalized ratio (INR) of 2 to 3 from June 2006 to August 2009; (2) ASA 81 mg daily (n = 18) from September 2009 to August 2011 with a target INR of 1.5 to 2; and (3) ASA 325 mg daily from September 2011 to November 2014 with a target INR of 2 to 3 (n = 70). Hemorrhagic and thrombotic outcomes were retrieved ≤ 365 days after implantation. Cumulative survival free from adverse events was calculated using Kaplan-Meier curves and Cox proportional hazard ratios were generated. Hemorrhagic events occurred in 6 patients on ASA 81 mg+dipyridamole (26%; 0.42 events per patient year; mean INR at event, 2.2), 4 patients on ASA 81 mg (22%; 0.38 events per patient year; mean INR at event, 2.0), and in 38 patients on ASA 325 mg (54%; 1.4 events per patient year; mean INR at event, 2.2); P = 0.004. Patients on ASA 325 mg had a higher adjusted hazard ratio of 2.9 (95% confidence interval, 1.2-7.0 versus ASA 81 mg+dipyridamole; P = 0.02) and 3.4 (95% confidence interval, 1.2-9.5 versus ASA 81 mg; P = 0.02) for hemorrhagic events. Thrombotic events rates were not different between groups.. High-dose ASA in Heart Mate II patients treated concomitantly with warfarin is associated with an increased hazard of bleeding but does not reduce thrombotic events.

Topics: Adult; Aged; Anticoagulants; Aspirin; Chi-Square Distribution; Dipyridamole; Disease-Free Survival; Drug Therapy, Combination; Female; Heart Failure; Heart-Assist Devices; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; New York City; Platelet Aggregation Inhibitors; Prevalence; Proportional Hazards Models; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome; Ventricular Function, Left; Warfarin

Heart failure (HF) patients are at high risk of having drug-related problems (DRPs). We aim to describe the frequency, types, and temporal occurrence of DRPs in Taiwanese HF outpatients receiving case management.. In this study, we included 141 patients from HF clinics in three hospitals in Taiwan from October 2008 to December 2010. Nurse case managers at each of the participating sites registered case report forms (CRFs) for patients during clinic visits. DRPs were classified using the Pharmaceutical Care Network Europe Foundation (PCNE) classification system and documented by pharmacists after reviewing CRFs and participating in multidisciplinary team discussions.. For 141 clinic participants, the average duration of medication use was 17 months, and 796 DRPs were reported. The DRPs most frequently recorded were the need for laboratory tests (32.7% of total DRPs), followed by potential interaction (29.6%), nonallergic side effects (13.3%), and insufficient awareness of health and disease (9.5%). The drugs most frequently causing a DRP were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, warfarin, spironolactone, and β-blockers. The incidence rates of total DRPs was maximal during the initial 3 months of medication treatment, whereas the incidence rates of each category of DRPs showed multiform changes over time among various drug classes.. In Taiwan where the clinical pharmacist system is not well organized, HF outpatients still had a high prevalence of DRPs despite intensive monitoring by nurse case managers. Clinical pharmacists play critical roles in detecting potential DRPs during long-term medication treatment for this population.

Topics: Adrenergic beta-Antagonists; Aged; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Case Management; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Male; Middle Aged; Outpatients; Prospective Studies; Spironolactone; Taiwan; Warfarin

Topics: Aged; Aspirin; Echocardiography, Transesophageal; Esophageal Mucosa; Heart Failure; Hemorrhage; Humans; Male; Warfarin

Topics: Angiodysplasia; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Pyrazoles; Pyridones; Ventricular Function, Left; Warfarin

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

Topics: Aspirin; Atrial Fibrillation; Clinical Laboratory Techniques; Coronary Artery Disease; Fibrinolysis; Fibrinolytic Agents; Heart Diseases; Heart Failure; Humans; Thrombelastography; Thrombosis; Tissue Array Analysis; Warfarin

The purpose of this study was to investigate the possible interaction between warfarin and linezolid in patients with a left ventricular assist system (LVAS) for the treatment of severe heart failure.. Patients with LVAS who were treated with linezolid for the treatment of infections from January 2003 to March 2013 were identified from medical records. The impact of linezolid on the clotting function, as well as the dose of warfarin during the first 10 days of linezolid therapy, was investigated. The mean prothrombin time-international normalized ratio (PT-INR) and mean doses of warfarin during 7 days before and 10 days after the initiation of linezolid therapy were calculated for individual patients. The PT-INR per mg of WF dose on the previous day (X) was calculated. The warfarin dose, PT-INR, and warfarin sensitivity index (WSI) value before and after the initiation of linezolid were compared to evaluate the impact of linezolid on the effect of warfarin.. Sixteen patients were enrolled in the study. Although the mean PT-INR increased from 3.74 to 4.06, no significant difference was observed (p=0.05). A significant difference was observed in the mean dose of warfarin before and after the initiation of linezolid administration, with a decrease from 3.23 to 2.69 mg/day (p=0.001). In contrast, the mean WSI value significantly increased from 1.37 to 1.82 (p=0.014). After 10 days of linezolid administration, the mean X values increased over the baseline value by 31.7%.. These findings suggest that co-administration of linezolid results in increased PT-INR in patients with LVAS treated with warfarin.

Topics: Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Tests; Drug Interactions; Female; Heart Failure; Heart-Assist Devices; Humans; International Normalized Ratio; Japan; Linezolid; Male; Prothrombin Time; Warfarin

Antithrombotic therapy could trigger diffuse alveolar hemorrhage (DAH), and there are several case reports of DAH that occurred during antithrombotic therapy (DAH-AT). However, little is known about the clinical features and outcomes of DAH-AT. The purpose of this study was to clarify the features and mortality of DAH-AT.. 76 consecutive patients with DAH who were admitted to our hospital between January 2003 and April 2014 were retrospectively reviewed to identify the clinical features and outcomes of DAH-AT. The primary outcome was 90-day mortality.. Of the 76 patients with DAH, 39 patients (51 %) had DAH-AT, and 37 patients (49 %) had DAH that occurred with no antithrombotic therapy (DAH-NAT). Of the patients with DAH-AT, 25 (64 %) were taking aspirin, 14 (36 %) were taking warfarin, 5 (13 %) were taking clopidogrel sulfate, and 4 (10 %) were taking cilostazol. Pre-existing cardiac disease was present in 23 (59 %) DAH-AT cases and 5 (14 %) DAH-NAT cases. Logistic regression analysis was used to assess the effect of antithrombotic therapy on the mortality of DAH patients, and no significant difference in survival was seen with antithrombotic therapy (OR 1.18, 95 % CI 0.38-3.78).. Antithrombotic therapies had no effect on the 90-day mortality of DAH patients.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Cilostazol; Clopidogrel; Connective Tissue Diseases; Female; Fibrinolytic Agents; Heart Failure; Hemorrhage; Humans; Infections; Lung Diseases; Male; Middle Aged; Neoplasms; Pneumonia; Pulmonary Alveoli; Retrospective Studies; Survival Rate; Tetrazoles; Ticlopidine; Vasculitis; Warfarin

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.. We used the "National Health Insurance Research Database" in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively.. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94).. In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Topics: Administration, Oral; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Insurance Claim Review; Intracranial Hemorrhages; Male; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Risk Assessment; Sex Distribution; Stroke; Taiwan; Vascular Diseases; Warfarin

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

To identify the factors influencing the prognosis of patients with acute pulmonary embolism(PE) and to establish a prognostic model.. The clinical data of 331 patients (141 males and 190 females, aged 9 to 87 years ) with acute PE in Fujian Hospital from January 2007 to September 2013 were analyzed. Univariate analysis and logistic regression analysis were used for selecting the independent prognostic factors for acute PE. Based on logistic regression analysis, a prognostic model for PE was established.. Univariate analysis showed that statistically significant (all P<0.05) factors influencing the prognosis of PE were diabetes, tricuspid systolic murmur, body temperature, respiratory rate, heart rate, aspartate aminotransferase, triglycerides, abnormal ECG, mechanical ventilation, circulatory failure during hospitalization, risk stratification of PE, types of treatment, and use of low-molecular-weight heparin and Warfarin. Logistic regression analysis showed that recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, circulatory failure during hospitalization and mechanical ventilation were independent factors for poor prognosis of PE, while combined use of low-molecular-weight heparin and Warfarin was a protective factor for the prognosis of PE. The Fisher prognostic model equation was y=0.144+ 1.266x1+ 0.869x2+ 1.794x3-0.517x4+ 3.555x5+ 0.661x6. The accuracy of the Fisher discriminant function was 93.0%.. Recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, shock during hospitalization and mechanical ventilation were signs of poor prognosis for PE, while combined use of low-molecular-weight heparin and Warfarin were beneficial for the prognosis. The discriminant function based on these data can be helpful for predicting the prognosis of patients with PE.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Heart Failure; Heart Murmurs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Prognosis; Pulmonary Embolism; Risk Assessment; Triglycerides; Warfarin; Young Adult

Anticoagulation with warfarin following bioprosthetic mitral valve replacement (BMVR) is recommended by multiple practice guidelines. We assessed practice variability and patient characteristics associated with warfarin prescription following BMVR.. We analyzed 7,637 patients in the Society of Thoracic Surgeons Database (January 1, 2008 to June 30, 2011) who were discharged following isolated primary nonemergent BMVR. Patients requiring preoperative warfarin, those with preoperative atrial fibrillation, or those with a contraindication to warfarin were excluded. The association between patient, hospital, and surgeon characteristics and warfarin prescription were evaluated.. Fifty-eight percent of this cohort (median age, 66 years; female sex, 58.7%) was prescribed warfarin. Patients receiving warfarin were older (67 vs 65 years; P < .0001), were less likely to have had preoperative stroke (9.3% vs 12.1%; P < .001), CHF (51.4% vs 54.1%; P < .02), or dialysis (4.9% vs 9.0%; P < 0.001), and had a longer postoperative length of stay (8.0 vs 7.0 days; P < 0.01). Warfarin was prescribed less often for patients with postoperative GI events (44.4% vs 55.6%; P < .001) but more often for patients with postoperative myocardial infarction (75.8% vs 24.2%; P < .001) or new atrial fibrillation (68% vs 32%; P < .001) and those requiring blood transfusions intraoperatively (55.7% vs 44.3%; P < .001) or postoperatively (57% vs 43%; P < .03). Similar rates of warfarin prescription were observed in patients requiring reoperation for bleeding (54.9% vs 45.1%; P = .20) and those with postoperative stroke (53.6 % vs 46.4 %; P = .30). After adjusting for patient characteristics, significant surgeon and hospital variation in warfarin prescription at hospitals was observed.. Although patient characteristics and postoperative events may be associated with the prescription of warfarin following BMVR, substantial surgeon and hospital variability remains. This variability largely ignores the established practice guidelines and warrants further study to define the optimal anticoagulation strategy in patients undergoing BMVR.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Bioprosthesis; Blood Loss, Surgical; Blood Transfusion; Databases, Factual; Female; Guideline Adherence; Heart Failure; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Length of Stay; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Multivariate Analysis; Myocardial Infarction; Patient Discharge; Postoperative Complications; Postoperative Hemorrhage; Practice Guidelines as Topic; Practice Patterns, Physicians'; Renal Dialysis; Stroke; Warfarin

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

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

In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments.. In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups.. Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04).. In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Topics: Aged; Aspirin; Cardiovascular Diseases; Cerebral Hemorrhage; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Warfarin

The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation.. Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin.. The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m(2). The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose.. Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Heart Failure; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Male; Middle Aged; Rivaroxaban; Stroke; Thromboembolism; Warfarin

The aim of this study was to determine whether the CHA. CHA. The CHA

Topics: Aged; Anticoagulants; Aspirin; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Stroke Volume; Systole; Warfarin

Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke-preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) ≥70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR ≥70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR ≥70%.. Within the community-based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR ≥70% in an initial 6-month period (TTR1; months 4-9), we described the distribution of TTR2 (months 10-15) and assessed multivariable correlates of persistent TTR ≥70%. Of patients with TTR1 ≥70%, 57% persisted with TTR2 ≥70% and 16% deteriorated to TTR2 <50%. Only initial TTR1 ≥90% (adjusted odds ratio 1.47, 95% CI 1.07-2.01) independently predicted TTR2 ≥70%. Heart failure was moderately associated with marked deterioration (TTR2 <50%); adjusted odds ratio 1.45, 95% CI 1.00-2.10.. Nearly 60% of AF patients with high-quality TTR1 on warfarin maintained TTR ≥70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6-month period. Our analyses support watchful waiting for AF patients with initial high-quality warfarin anticoagulation before considering alternative anticoagulants.

Topics: Aged; Atrial Fibrillation; Cohort Studies; Comorbidity; Crotalid Venoms; Female; Heart Failure; Humans; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Stroke; Warfarin

Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration.. A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting.. The final model had five variables: warfarin indication, insurance status, number of doctor's visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction.. Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Aged; Algorithms; Anticoagulants; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Insurance, Health; Male; Middle Aged; Models, Theoretical; Proportional Hazards Models; Prospective Studies; Smoking; Time Factors; Warfarin

The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain.. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years.. Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported.. Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Topics: Aged, 80 and over; Anemia; Anticoagulants; Comorbidity; Female; Heart Failure; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Recurrence; Registries; Renal Insufficiency; Spain; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Chest Pain; Coronary Artery Disease; Drug-Eluting Stents; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Tachycardia, Ventricular; Treatment Outcome; Warfarin

We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD).. Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors.. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009).. Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Comorbidity; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Warfarin

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

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

Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk.. Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.

Topics: Adolescent; Adult; Aged; Aortic Valve Stenosis; Blood Platelets; Cohort Studies; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Heart-Assist Devices; Hemorrhage; Heparin; Humans; Male; Middle Aged; Platelet Activation; Platelet Glycoprotein GPIb-IX Complex; Platelet Membrane Glycoproteins; Stress, Mechanical; Thrombosis; von Willebrand Factor; Warfarin; Young Adult

Topics: Anesthesia, General; Anticoagulants; Capnography; Cardiopulmonary Resuscitation; Clopidogrel; Defibrillators, Implantable; Epinephrine; Female; Heart Failure; Heart Ventricles; Heart-Assist Devices; Hemorrhage; Humans; Middle Aged; Monitoring, Intraoperative; Platelet Aggregation Inhibitors; Ticlopidine; Treatment Outcome; 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

Topics: Aspirin; Heart Failure; Humans; Stroke; Stroke Volume; Warfarin

Topics: Aspirin; Heart Failure; Humans; Stroke; Stroke Volume; Ventricular Function, Left; Warfarin

Risk factors of stroke/thromboembolism (TE) and major bleeding, and incidence of these events in specific age categories in warfarin-treated patients with mechanical heart valves (MHV) are uncertain. Our objective was to calculate event rates in specific age categories and identify risk factors for adverse events.. We identified 4,810 treatment periods with MHV between January 2006 and December 2011 in the Auricula and Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. There were 3,751 treatment periods with aortic valve replacements (AVR) and 866 with mitral valve replacements (MVR). Median follow-up time was 4.5 years (IQR, 1.5-6.0). Time in therapeutic range with warfarin for patients with AVR was 74.2% for international normalized ratio of 2.0 to 3.0, with 72% of the patients having this target range. Rate of stroke/TE for AVR and MVR was 1.3 and 1.6 per 100 patient years, respectively (P=.20). The rate of first major bleeding was 2.6 and 3.9 per 100 patient years with AVR and MVR, respectively (P<.001). By multivariate analysis for AVR, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03 per year) and previous stroke (HR, 2.4; 95% CI, 1.7-3.5) emerged as independent risk factors for stroke/TE. Heart failure (HR, 0.9; 95% CI, 0.6-1.4) and atrial fibrillation (HR, 1.0; 95% CI, 0.7-1.4) were not associated to stroke/TE. For major bleeding events, age (HR, 1.02; 95% CI, 1.01-1.03 per year) and previous major bleeding (HR, 2.5; 95% CI, 1.9-3.3) emerged as independent risk factors for AVR.. In a nationwide cohort study with MHV and high time in therapeutic range, heart failure and atrial fibrillation did not appear as risk factors of stroke/TE.

Topics: Aged; Anticoagulants; Aortic Valve; Atrial Fibrillation; Cohort Studies; Female; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Mitral Valve; Multivariate Analysis; Proportional Hazards Models; Risk Factors; Stroke; Sweden; Thromboembolism; Warfarin

Modern data on the need to appoint oral anticoagulants in patients with atrial fibrillation and concomitant heart failure. Based on the Phase III study analysis comparing the direct oral anticoagulant warfarin and meta-analysis shows that taking direct oral coagulants no less effective and safer than warfarin in patients with atrial fibrillation and heart failure, which affects significantly fewer intracranial and heavy bleeding.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Warfarin

Topics: Anticoagulants; Aspirin; Enoxaparin; Female; Heart Failure; Heart Transplantation; Heart Ventricles; Heart-Assist Devices; Humans; Middle Aged; Thrombosis; Treatment Outcome; Warfarin

Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted.. Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users. Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association.. Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation in Denmark, warfarin initiation has declined since the introduction of dabigatran in August 2011. Dabigatran is the most frequently used alternative option to warfarin; however, use of rivaroxaban and apixaban is increasing. Patients initiated with rivaroxaban or apixaban in general have a higher predicted stroke and bleeding risks compared with warfarin or dabigatran initiators.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Denmark; Female; Heart Failure; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Registries; Renal Insufficiency, Chronic; Rivaroxaban; Sex Factors; Stroke; Thiophenes; Warfarin

The use of oral anticoagulation in patients with heart failure in sinus rhythm remains controversial as previous large randomized controlled trials (RCTs) have not shown a survival benefit. However, heterogeneity exists among heart failure patients and it is possible that high-risk subgroups may benefit from anticoagulation (warfarin). We hypothesize that one such subgroup are patients with heart failure and pulmonary hypertension (PH), conditions associated with coagulation abnormalities.. We conducted a retrospective, population-based, longitudinal cohort study in patients with left ventricular systolic dysfunction (LVSD) and PH [defined as a right ventricular systolic pressure (RVSP) >35 mmHg] identified from echocardiograms performed between January 1994 to May 2011. This data was linked using a unique patient-specific identifier to community-dispensed prescriptions, hospital admissions, and mortality data. For comparison, we included patients with LVSD and no PH.. A total of 2619 subjects with LVSD and a measurable RVSP were identified (mean ± SD age of 73 ± 12 years); 1606 out of 2619 had PH and 1013 out of 2619 had no PH. The overall mean follow-up period was 2.56 ± 3.0 years. In patients with LVSD and PH, the use of warfarin was associated with an improved survival [hazard ratio (HR) = 0.72 95% confidence interval (CI) 0.58-0.90, P = 0.0003], fewer non-cardiovascular disease-related deaths (HR = 0.65, 95%CI 0.49-0.87, P = 0.0033 and showed a trend towards reduced cardiovascular disease-associated mortality (HR = 0.72, 95%CI 0.51-1.02). Warfarin did not improve survival in those with LVSD with no PH.. In patients with both LVSD and PH, the use of warfarin is associated with a 28% reduction in mortality. Further prospective trials are required to confirm our findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cohort Studies; Female; Heart Failure; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Systole; Ventricular Dysfunction, Left; Warfarin

Several trials have compared aspirin or warfarin with either placebo or no antithrombotic drug therapy in a total of a few hundred patients with heart failure in sinus rhythm and no particular thrombotic risk.There is no evidence that antiplatelet or anticoagulant therapy reduces mortality or cardiovascular events, but antithrombotic drugs can provoke severe bleeding.

Topics: Aspirin; Fibrinolytic Agents; Heart Failure; Hemorrhage; Humans; Patient Safety; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Unnecessary Procedures; Warfarin

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs).. CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events.. A prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels.. A total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001).. Levels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Hemolysis; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Prosthesis Failure; Thromboembolism; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Cardiac Tamponade; Diastole; Heart Failure; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Male; Middle Aged; Postoperative Complications; Pulsatile Flow; Sternotomy; Systole; Thoracotomy; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Female; Heart Failure; Humans; Male; Stroke; Warfarin

Among patients receiving oral anticoagulation for atrial fibrillation (AF), heart failure (HF) is associated with poor anticoagulation control. However, it is not known which patients with heart failure are at greatest risk of adverse outcomes. We evaluated 62,156 Veterans Health Administration (VA) patients receiving warfarin for AF between 10/1/06-9/30/08 using merged VA-Medicare dataset. We predicted time in therapeutic range (TTR) and rates of adverse events by categorising patients into those with 0, 1, 2, or 3+ of five putative markers of HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline phosphatase> 150 U/l, serum sodium< 130 mEq/l, any receipt of metolazone, and any inpatient admission for HF exacerbation. These risk categories predicted TTR: patients without HF (referent) had a mean TTR of 65.0 %, while HF patients with 0, 1, 2, 3 or more markers had mean TTRs of 62.2 %, 57.2 %, 53.5 %, and 50.7 %, respectively (p< 0.001). These categories also discriminated for major haemorrhage well; compared to patients without HF, HF patients with increasing severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p< 0.001). However, although patients with HF had an elevated hazard for bleeding compared to those without HF, these categories did not effectively discriminate risk of ischaemic stroke across HF. In conclusion, we developed a HF severity model using easily available clinical characteristics that performed well to risk-stratify patients with HF who are receiving anticoagulation for AF with regard to major haemorrhage.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Databases, Factual; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs; Veterans Health; Warfarin; Young Adult

Adequate anticoagulation represents a major problem for left ventricle assist device (LVAD) utilization in patients awaiting heart transplantation as well as for regeneration of the native heart. The proper management of hemostatic abnormalities during LVAD support may improve survival by reducing the incidence of hemorrhagic and/or thromboembolic complications.. A 40-year-old man with implanted pulsatile LVAD due to dilated cardiomyopathy received aspirin and warfarin. The patient underwent serial weekly monitoring of hemostatic biomarkers including international normalization ratio, prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen, D-dimer, platelet aggregation induced by adenosine diphosphate and arachidonic acid, platelet count, and mean platelet volume. The external pump was exchanged three times - twice because of a clot formation in the blood chamber of the pump, and once according to the standard protocol.. LVAD use was consistently associated with enhanced adenosine diphosphate-induced platelet aggregation independent from the timing of clot formation or external pump exchange. Among coagulation indices, increased D-dimer holds predictive value for clot formation. The fibrinogen level peaked before the first pump exchange and was twice as high than the average values. Gradual improvement in exercise capacity was observed 2 years after implantation, after which the patient underwent a controlled stress test in the stop mode of the LVAD and the device was successfully explanted.. Serial assessment of hemostatic biomarkers may benefit and triage LVAD patients. Consistent platelet activation during long-term LVAD may justify the addition of clopidogrel, while high D-dimer and/or elevated fibrinogen may indicate adding heparin to the conventional antithrombotic regimen. Randomized evidence is needed to test such a hypothesis.

Topics: Adult; Anticoagulants; Aspirin; Biomarkers; Clopidogrel; Drug Therapy, Combination; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heart Failure; Heart Ventricles; Heart-Assist Devices; Heparin; Humans; Male; Platelet Activation; Platelet Aggregation; Ticlopidine; Warfarin

Although atrial fibrillation (AF) is a known complication of amyloidotic cardiomyopathy (AC), a precise pathophysiological and prognostic characterization is not available. We therefore aimed to assess prevalence, incidence, risk factors and prognostic significance of AF in light-chain (AL), hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC.. Retrospective study of 262 patients with AC (123 AL, 94 m-ATTR, 45 wt-ATTR) from a single center.. AF prevalence was 15% (AL 9%, m-ATTR 11%, wt-ATTR 40%). During a median follow-up of 1.2 years 11 patients developed AF (2.1% person-years). Age, heart failure (HF), left ventricular (LV) ejection fraction, renal involvement, left atrial size and right atrial pressure were independently associated with AF. AF was associated with incident HF but not with increased mortality. All AF patients were prescribed warfarin and none suffered thromboembolic events.. In AC the prevalence of AF varies widely according to etiology with a mean value of 15% that reaches 40% in wt-ATTR amyloidosis. Age, HF, LV ejection fraction, left atrial size and right atrial pressure were the main independent risk factors, while wall thickness and etiology were not the main independent risk factors. AF does not seem to impact all-cause mortality but was strongly associated with prevalent and incident HF.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amyloidosis; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Female; Heart Failure; Humans; Incidence; Italy; Longitudinal Studies; Male; Middle Aged; Prealbumin; Prevalence; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Survival Analysis; Thromboembolism; Ventricular Function, Left; Warfarin

Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice.. Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR.. Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) (P < .0001).. Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Frail Elderly; Heart Failure; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Registries; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Heart failure (HF) has been associated with an elevated international normalized ratio (INR) in patients on warfarin.. Compare warfarin sensitivity during hospital admission for HF exacerbation and chronic obstructive pulmonary disease (COPD) exacerbation with admissions unrelated to HF or COPD (controls) as well as during disease stability.. We conducted a case-controlled observational study. Patients admitted to a tertiary teaching hospital for HF exacerbation (n = 37), COPD exacerbation (n = 26), and admissions unrelated to HF or COPD (controls, n = 60) were included. Warfarin sensitivity (INR per daily mg dose of warfarin) at admission was compared to periods of disease stability and also compared between the 3 groups.. The increase in warfarin sensitivity at admission was 94% for HF patients (P < 0.0001), 59% for COPD (P = 0.003) patients, and 24% for controls (P = 0.002). HF patients with New York Heart Association (NYHA) class 3 and 4 and NYHA class 1 and 2 experienced changes in warfarin sensitivity of 125% (P = 0.006) and 50% (P = 0.13) at admission. HF patients had higher warfarin sensitivity at admission (mean = 1.62 [SD = 1.27]) compared to the control group (0.91 [0.52], P < 0.0001) and COPD group (1.03 [0.79], P = 0.04). and required greater intervention with vitamin K than controls (14% vs 0%, P = 0.007).. HF and COPD patients were more sensitive to warfarin during disease exacerbation, with HF exacerbation having the largest impact, resulting in clinically significant management implications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Disease Progression; Female; Heart Failure; Hospitalization; Humans; International Normalized Ratio; Male; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin

Anticoagulation therapy with warfarin is recommended for stroke prevention in patients with atrial fibrillation (AF) or atrial flutter (AFL) whose risks for stroke are high. However, previous studies suggest that warfarin is markedly underused. This study aims to investigate the incidence and risk factors of warfarin underutilization in patients with high risk of stroke in Korea.. This was a cross-sectional study using the data of 2009 from National Patients Sample compiled by the Health Insurance Review and Assessment Service. Patients with high risk of thromboembolism were identified with congestive heart failure, hypertension, age ≥75 years, diabetes, and prior stroke (CHADS2) score ≥2. High-risk patients of bleeding were excluded using Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) score >4. Warfarin and antithrombotic therapy underutilization were defined and estimated in high-risk patients. Any demographic and clinical factors associated with warfarin and antithrombotic therapy underutilization were explored using a logistic regression model.. Of the national patient sample, 15,885 patients were identified with AF or AFL. Among them, a total of 8475 patients who had an admission history, CHADS2 ≥2, and ATRIA score ≤4 were included in the analysis. From the study sample, warfarin underutilization and antithrombotic therapy underutilization were estimated to be 64.0% and 20.4%, respectively. Predictors of warfarin underutilization include female sex, age ≥80 years, lower CHADS2 score, and insurance type (Medical Aid program).. A high portion of AF/AFL patients with CHADS2 score ≥2 were undertreated with warfarin. As ischemic stroke is one of the leading causes of death in Korea, a more aggressive approach to prevent stroke in patients with AF/AFL is required.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Cross-Sectional Studies; Diabetes Complications; Female; Health Status Indicators; Heart Failure; Hospitalization; Humans; Hypertension; Incidence; Logistic Models; Male; Middle Aged; Republic of Korea; Risk Factors; Stroke; Thromboembolism; Warfarin

Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness.

Topics: Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Dilated; Echocardiography; Heart Atria; Heart Diseases; Heart Failure; Heparin; Humans; Male; Middle Aged; Recurrence; Thrombosis; Warfarin

To evaluate clinical characteristics and outcome of acute ischemic stroke patients with atrial fibrillation.. Consecutive acute ischemic stroke patients who were hospitalized in the neurology department of General Hospital of Jinan Military Region were prospectively recruited from August 2010 to November 2013.The baseline datum including age, sex, National Institute of Health Stroke Scale (NIHSS), type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction), serum creatinine, serum albumin levels etc.were recorded.Atrial fibrillation (AF) was defined as a history of persistent atrial fibrillation or paroxysmal atrial fibrillation, supported by past electrocardiogram or diagnosed by the attending physicians based on physical examination, electrocardiogram and/or 24-hour electrocardiogram monitoring during hospitalization. Outcome was assessed by modified Rankin Scale (mRS) which was obtained 180 days after stroke by telephone interview (mRS ≤ 2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis), and death defined as all-cause mortality. Multivariate regression model was used to analyze predictors of mortality and disability.. Of the 965 patients included in this study, 113 (11.71%) had AF; valvular AF was observed in 11 patients (9.7%) among them.Only 4 patients with valvular AF and none of the patients with non-valvular AF took warfarin before the stroke event. 14.2% (16/113) acute ischemic stroke patients with AF took aspirin. Compared to patients without AF, patients with AF had a higher NIHSS score on admission (median 11 vs 5, P=0.000); were more often with diabetes (26.55% vs 9.74%, P=0.028), congestive heart failure (12.37% vs 11.03%, P=0.000), prior stroke (31.86% vs 21.83%, P=0.023), total anterior circulation infarct subtype (51.33% vs 19.37%, P=0.000); they were less often smokers (20.35% vs 37.32%, P=0.000), alcohol consumers (13.27% vs 27.58%, P=0.001), partial anterior circulation infarction subtype (24.78% vs 36.74%, P=0.012), lacunar infarct subtype (0 vs 17.61%, P=0.000); they had less often experienced myocardial infarction (11.50% vs 11.74%, P=0.041). AF was a significant independent prognostic factor for long-term poor outcomes (OR=2.227, 95%CI: 1.262-3.933, P=0.006).. Oral anticoagulants are underused in AF patients.Brain infarction patients with AF is more severe than patients without AF; have higher frequency of total anterior circulation infarct subtype, prior stroke and lower frequency of lacunar infarct subtype. AF is a significant independent prognostic factor for long-term poor outcome in patients with acute brain infarction.

Topics: Anticoagulants; Atrial Fibrillation; Brain Infarction; Diabetes Mellitus; Heart Failure; Humans; Myocardial Infarction; Prognosis; Stroke; Treatment Outcome; Warfarin

Postdischarge adherence and long-term persistence in the use of warfarin among patients with heart failure and atrial fibrillation without contraindications have not been fully described.. We identified patients with heart failure and atrial fibrillation who were ≥ 65 years old, eligible for warfarin, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry from January 1, 2006, to December 31, 2009. We used linked Medicare prescription drug event data to measure adherence and persistence. The main outcome measures were rates of prescription at discharge, outpatient dispensing, discontinuation, and adherence as measured by the medication possession ratio. We hypothesized that adherence to warfarin would differ according to whether patients received the prescription at discharge. Among 2,691 eligible patients, 1,856 (69.0%) were prescribed warfarin at discharge. Patients prescribed warfarin at discharge had significantly higher prescription fill rates within 90 days (84.5% vs 12.3%; P < .001) and 1 year (91.6% vs 16.8%; P < .001) and significantly higher medication possession ratios (0.78 vs 0.63; P < .001). Among both previous nonusers and existing users, fill rates at 90 days and 1 year and possession ratios were significantly higher among those prescribed warfarin at discharge.. One-third of eligible patients with heart failure and atrial fibrillation were not prescribed warfarin at discharge from a heart failure hospitalization, and few started therapy as outpatients. In contrast, most patients who were prescribed warfarin at discharge filled the prescription within 90 days and remained on therapy at 1 year.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Causality; Drug Prescriptions; Female; Heart Failure; Humans; Male; Medicare; Medication Adherence; Outcome Assessment, Health Care; Outpatients; Patient Discharge; Registries; Stroke; United States; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Prescriptions; Heart Failure; Humans; Male; Patient Discharge; Practice Guidelines as Topic; Registries; Warfarin

Topics: Adult; Aged; Anticoagulants; Aspirin; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Warfarin; Withholding Treatment

Left ventricular assist devices (LVADs) have been increasingly used for 20 years in terminally ill patients with advanced heart failure or awaiting cardiac transplantation. Despite improvement in morbidity and mortality from use of these devices, quality of life may be limited by cataract. Access to cataract surgery in this predominantly elderly population is essential but limited by unfamiliarity with these devices. We describe phacoemulsification and intraocular lens implantation in 2 patients with LVADs. The patients had extensive preoperative cardiology evaluations and were instructed to continue warfarin through the day of surgery. Monitored sedation was used with fentanyl and midazolam. Both patients experienced significant improvement in visual acuity and quality of life. Neither experienced intraoperative hemodynamic instability. Cataract surgery may be safely performed in patients with LVAD support when adequate monitoring resources are available.. No author has a financial or proprietary interest in any material or method mentioned.

Topics: Activities of Daily Living; Aged; Anticoagulants; Cardiomyopathy, Dilated; Cataract; Heart Failure; Heart-Assist Devices; Humans; Lens Implantation, Intraocular; Male; Middle Aged; Phacoemulsification; Quality of Life; Warfarin

This study aimed to describe the contemporary aetiology, clinical characteristics and mortality and its predictors in heart failure (HF) in Tanzania.. Design; Prospective observational study. Setting; Cardiovascular Center of the Muhimbili National Hospital in Dar es Salaam, Tanzania. Patients ≥18 years of age with HF defined by the Framingham criteria.. All-cause mortality.. Among 427 included patients, 217 (51%) were females and the mean (SD) age was 55 (17) years. HF aetiologies included hypertension (45%), cardiomyopathy (28%), rheumatic heart disease (RHD) (12%) and ischaemic heart disease (9%). Concurrent atrial fibrillation (AF), clinically significant anaemia, diabetes, tuberculosis and HIV were found in 16%, 12%, 12%, 3% and 2%, respectively, while warfarin was used in 3% of the patients. The mortality rate, 22.4 per 100 person-years over a median follow-up of 7 months, was independently associated with AF, HR 3.4 (95% CI 1.6 to 7.0); in-patient 3.2 (1.5 to 6.8); anaemia 2.3 (1.2 to 4.5); pulmonary hypertension 2.1 (1.1 to 4.2) creatinine clearance 0.98 (0.97 to 1.00) and lack of education 2.3 (1.3 to 4.2).. In HF in Tanzania, patients are younger than in the developed world, but aetiologies are becoming more similar, with hypertension becoming more and RHD less important. Predictors of mortality possible to intervene against are anaemia, AF and lack of education.

Topics: Anemia; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Educational Status; Female; Heart Failure; HIV Infections; Humans; Kidney Function Tests; Male; Middle Aged; Mortality; Prognosis; Prospective Studies; Tanzania; Tertiary Care Centers; Tuberculosis; Warfarin

The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely on cardioembolic and bleeding risk stratification. Sharing some risk factors, schemes to predict thrombotic and bleeding risk are expected not to be independent, yet the degree of their association has never been clearly quantified.. We described the cardioembolic (Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack [CHADS2]/Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack, Vascular disease, Age 65-75, Sex category i.e. females [CHA2DS2-VASc]) and bleeding risk (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly [HAS-BLED]) co-distribution among patients of the Euro Heart Survey on atrial fibrillation. We measured the within-patient correlation (Spearman) and concordance between the 2 types of score and score-based risk categorization (low, intermediate, high). The score-based predicted risk co-classification was then related to the observed 1-year stroke and bleeding occurrence.. In 3920 patients, we found a between-scores correlation of 0.416 (P < .001) between HAS-BLED and CHADS2, and 0.512 (P < .001) between HAS-BLED and CHA2DS2-VASc. In 89% (CHADS2/HAS-BLED) and 97% (CHA2DS2-VASc/HAS-BLED) of patients, the bleeding risk category was equal to or lower than their cardioembolic risk category (P < .001 for symmetry test). A complete concordance between risk categories was found in 39.6% (CHADS2/HAS-BLED) and 21.7% (CHA2DS2-VASc/HAS-BLED) of patients; 4.4% (CHADS2/HAS-BLED) and 7.7% (CHA2DS2-VASc/HAS-BLED) of patients had high cardioembolic risk/low bleeding risk or vice versa. A tendency for an increasing frequency of stroke was observed for increasing bleeding risk within cardioembolic risk categories and vice versa.. In a real-world population with atrial fibrillation, we confirmed that the cardioembolic and bleeding risk classifications are correlated but not exchangeable. It is then worth verifying the advantages of a strategy adopting a combined risk assessment over a strategy relying only on the cardioembolic risk evaluation.

Topics: Age Distribution; Aged; Alcohol Drinking; Anticoagulants; Aspirin; Atrial Fibrillation; Diabetes Complications; Europe; Female; Health Surveys; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Risk Assessment; Sex Distribution; Stroke; Substance-Related Disorders; Thromboembolism; Warfarin

We prospectively evaluated long-term clinical outcomes of patients diagnosed with isolated left ventricular noncompaction (ILVNC) and heart failure from a sub-Saharan African population.. Patients in this single-center study were followed at a tertiary care institution. Clinical follow-up was performed with the use of protocol-driven echocardiographic screening for ventricular thrombus every 4 months. Warfarin was maintained or initiated only if thrombus was detected with the use of echocardiography. Fifty-five patients were followed for 16.7 ± 5.9 (range 12-33) months. All individuals had left ventricular (LV) ejection fraction <50% (mean 29.6 ± 11.8%). Of the 55 patients, 7 (12.7%) died, and sudden cardiac death was the cause in 5 (71.4%). There were no differences in baseline clinical, echocardiographic, or electrocardiographic characteristics between survivors and nonsurvivors. Recurrent heart failure developed in 12 patients (21.8%); 1 patient developed a ventricular arrhythmia. No thromboembolic or major bleeding complications occurred in the 16 patients on warfarin; 1 episode of thromboembolism occurred in the 39 patients not on warfarin. Mean survival probability at 33 months was 0.64.. Sudden cardiac death was the most common cause of death in patients with ILVNC and heart failure. Recurrent heart failure occurred in 21.8% of patients. Development of LV thrombus and cardioembolism is uncommon in this population.

Topics: Adult; Africa South of the Sahara; Anticoagulants; Death, Sudden, Cardiac; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Stroke Volume; Survival Analysis; Thrombosis; Ventricular Dysfunction, Left; Ventricular Function, Left; Warfarin

Anticoagulants such as warfarin are recommended for patients with atrial fibrillation (AF) to decrease stroke risk associated with thrombus formation in the left atrium (LA). In a subgroup of patients, however, warfarin is unable to prevent LA thrombus formation at therapeutic doses. This study characterized the clinical and echocardiographic features of patients having warfarin-resistant LA thrombus.Of the 1364 nonvalvular AF patients examined by transesophageal echocardiography, 431 received warfarin. A total of 10 patients (2.3% of warfarin-treated patients) exhibited LA thrombus formation even during warfarin treatment at a dose and duration sufficient for increasing the prothrombin time-international normalized ratio (PT-INR) to the therapeutic range for ≥ 30 days. Categorical regression analysis revealed that decreased LA appendage (LAA) flow velocity, greater LA spontaneous echocardiographic contrast (LASEC), and lower left ventricular ejection fraction (LVEF) significantly contributed to residual LA thrombus (P < 0.05 for all). Receiver operating characteristic (ROC) curve analysis indicated that higher right ventricular systolic pressure, which suggests LA pressure (area under curve, 0.85), LV mass index (0.81), and LA dimension (0.68), as well as lower LAA flow velocity (0.92) and LVEF (0.91) predicted warfarin resistant LA thrombus formation (all P < 0.05).These results suggest that blood stasis secondary to heart failure contributes to the formation of warfarin-resistant LA thrombus. We propose that therapies to increase LVEF should be administered together with warfarin for AF patients with heart failure to decrease stroke risk.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Echocardiography; Female; Heart; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Retrospective Studies; Thrombosis; Warfarin

Topics: Adult; Aged; Antibodies; Anticoagulants; Blood Coagulation; Factor X; Female; Heart Failure; Heart-Assist Devices; Heparin; Humans; Incidence; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Risk Factors; Thrombosis; Ventricular Dysfunction, Left; Warfarin

Warfarin-related nephropathy (WRN) is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR) >3.0) causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors.. During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea.. WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN.. WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Asian People; Creatinine; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Serum Albumin; Survival Analysis; Warfarin

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin.. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups.. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Embolism; Female; Heart Failure; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Stroke; Ventricular Dysfunction, Left; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Coronary Occlusion; Dabigatran; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Male; Percutaneous Coronary Intervention; Stroke; Transplantation; Warfarin

The clinical characteristics and long-term outcomes of patients presenting with acute pulmonary embolism (PE) during treatment with warfarin have not been described. Clinical details of all patients admitted to a tertiary institution from 2000-2007 with acute PE were retrieved retrospectively, baseline warfarin status and the international normalised ratio (INR) were recorded, and their outcomes tracked using a statewide death registry. Of 923 patients with clearly documented warfarin status included in this study, 83 (9%) were taking warfarin. Mean (± standard deviation) day-1 INR of those taking warfarin was 2.3 ± 0.9, with 67% of patients therapeutically anti-coagulated (INR ≥2.0) at presentation (49 patients with INR <2.5 and 34 with INR ≥2.5). Patients taking warfarin on admission were more likely to have heart failure, atrial fibrillation and valvular heart disease, with similar prevalence of malignancy and ischaemic heart disease, compared to patients not on warfarin. Total mortality of the cohort (mean follow-up 4.0 ± 2.5 years) was 31.6% (in-hospital mortality 1.5%), and was similar between warfarin and no warfarin groups. There was however a greater than four-fold increased risk of post-discharge death due to recurrent PE for the patients taking warfarin on admission (hazard ratio [HR] 4.43, 95% confidence interval [CI] 1.36-14.42, p=0.01). Among patients taking warfarin on admission, day-1 INR <2.5 significantly increased long-term all-cause mortality compared to INR ≥2.5 (adjusted HR 2.51, 95% CI 1.08-5.86, p=0.03). In conclusion, patients presenting with PE during treatment with warfarin have an increased risk of death from recurrent PE. Admission INR appears to have independent long-term prognostic importance in these patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; International Normalized Ratio; Male; Middle Aged; Prognosis; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Patients with heart failure are at higher risk for thromboembolic events, even in the absence of atrial fibrillation, but the effect of anticoagulation therapy on outcomes is uncertain.. With data from a clinical registry linked to Medicare claims, we estimated the adjusted associations between anticoagulation and 1-year outcomes with the use of inverse probability of treatment weighting. Eligible patients had an ejection fraction ≤35%, had no concurrent atrial fibrillation, were alive at discharge, and had not received anticoagulation therapy before admission. Of 13,217 patients in 276 hospitals, 1,140 (8.6%) received anticoagulation therapy at discharge. Unadjusted rates of thromboembolic events and major adverse cardiovascular events did not differ by receipt of anticoagulation therapy. Patients discharged on anticoagulation therapy had lower unadjusted rates of all-cause mortality (27.2% vs 32.3%; P < .001) and readmission for heart failure (29.4% vs 35.4%; P < .001) and higher rates of bleeding events (5.2% vs 2.8%; P < .001). After adjustment for probability of treatment and discharge medications, there were no differences in all-cause mortality (hazard ratio 0.92; 95% confidence interval 0.80-1.06) or readmission for heart failure (0.91, 0.81-1.02), but patients receiving anticoagulation therapy were at higher risk for bleeding events (2.09, 1.47-2.97).. Anticoagulation therapy at discharge is infrequent among older patients with heart failure and without atrial fibrillation. There were no statistically significant propensity-weighted associations between anticoagulation therapy and 1-year outcomes, except for a higher risk of bleeding.

Topics: Aged; Anticoagulants; Female; Heart Failure; Hemorrhage; Humans; Male; Outcome Assessment, Health Care; Patient Discharge; Patient Readmission; Registries; Thromboembolism; United States; Warfarin

This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS₂ score of ≥2 was defined as "higher" CHADS₂. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS₂ score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Decision Support Techniques; Diabetes Complications; Female; Heart Failure; Humans; Hypertension; International Normalized Ratio; Logistic Models; Longitudinal Studies; Male; Middle Aged; Risk Factors; Software; Stroke; Time Factors; Warfarin

Topics: Atrial Fibrillation; Brain Ischemia; Heart Failure; Humans; Stroke; Warfarin

The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses.. We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions.. Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups.. The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin.

Topics: Anticoagulants; Aspirin; Brain Damage, Chronic; Brain Ischemia; Cerebral Hemorrhage; Heart Failure; Humans; Intracranial Embolism; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Severity of Illness Index; Stroke; Stroke Volume; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Heart Failure; Humans; Male; Stroke; Warfarin

The intersection of heart failure (HF) and atrial fibrillation (AF) is common, but the burden of AF among black patients with HF is poorly characterized. We sought to determine the prevalence of AF, characteristics, in-hospital outcomes, and warfarin use associated with AF in patients hospitalized with HF as a function of race.. We analyzed data on 135 494 hospitalizations from January 2006 through January 2012 at 276 hospitals participating in the American Heart Association's Get With The Guidelines HF Program. Multivariable logistic regression models using generalized estimating equations approach for risk-adjusted comparison of AF prevalence, in-hospital outcomes, and warfarin use. In this HF population, 53 389 (39.4%) had AF. Black patients had markedly less AF than white patients (20.8% versus 44.8%, P < 0.001). Adjusting for risk factors and hospital characteristics, black race was associated with significantly lower odds of AF (adjusted odds ratio 0.52, 95% CI 0.48 to 0.55, P < 0.0001). There were no racial differences in in-hospital mortality; however, black patients had a longer length of stay relative to white patients. Black patients compared with white patients with AF were less likely to be discharged on warfarin (adjusted odds ratio 0.76, 95% CI 0.69 to 0.85, P < 0.001).. Despite having many risk factors for AF, black patients, relative to white patients hospitalized for HF, had a lower prevalence of AF and lower prescription of guideline-recommended warfarin therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Black or African American; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Prevalence; Risk Factors; Treatment Outcome; Warfarin; White People

Effective warfarin thromboprophylaxis requires maintaining anticoagulation within the recommended international normalized ratio (INR) range. INR testing rates and associations between testing and outcomes are not well understood.. INR testing rates after hospitalization for acute decompensated heart failure are suboptimal, and testing is associated with lower risks of mortality and adverse clinical events.. We conducted a retrospective cohort study of patients who were long-term warfarin users and were hospitalized for heart failure, had a medical history of atrial fibrillation or valvular heart disease, and were enrolled in fee-for-service Medicare. INR testing was defined as ≥1 outpatient INR test within 45 days after discharge. Using Cox proportional hazards models, we examined associations between testing and all-cause mortality, all-cause readmission, and adverse clinical events at 1 year.. Among 8558 patients, 7722 (90.2%) were tested. After 1 year, tested patients had lower all-cause mortality (23.5% vs 32.6%; P < 0.001) and fewer myocardial infarctions (2.0% vs 3.3%; P = 0.02). These differences remained significant after multivariable adjustment with hazard ratios of 0.72 (95% confidence interval [CI]: 0.63-0.84; P < 0.001) and 0.58 (95% CI: 0.41-0.83; P = 0.003), respectively. Differences in all-cause readmission, thromboembolic events, ischemic stroke, and bleeding events were not statistically significant.. Postdischarge outpatient INR testing in patients with heart failure complicated by atrial fibrillation or valvular heart disease was high. INR testing was associated with improved survival and fewer myocardial infarctions at 1 year but was not independently associated with other adverse clinical events.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Humans; Insurance, Pharmaceutical Services; International Normalized Ratio; Kaplan-Meier Estimate; Male; Medicare; Multivariate Analysis; Patient Discharge; Patient Readmission; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Warfarin

Topics: Atrial Fibrillation; Brain Ischemia; Clinical Trials as Topic; Heart Failure; Humans; Risk Factors; Stroke; Warfarin

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

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

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Male; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Aspirin; Heart Failure; Humans; 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

Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation..   To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu..   Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS(2) (Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification..   This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE..   Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS(2) score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors..   Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Echocardiography, Transesophageal; Female; Heart Failure; Humans; Hypertension; Hyperthyroidism; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Warfarin

The Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke (CHADS(2)) score is used to predict the need for oral anticoagulation for stroke prophylaxis in patients with atrial fibrillation. The Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65-74 years, Sex category (CHA(2)DS(2)-VASc) schema has been proposed as an improvement. Our objective is to determine how adoption of the CHA(2)DS(2)-VASc score alters anticoagulation recommendations.. Between 2004 and 2008, 1664 patients were seen at the University of Virginia Atrial Fibrillation Center. We calculated the CHADS(2) and CHA(2)DS(2)-VASc scores for each patient. The 2006 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for atrial fibrillation management were used to determine anticoagulation recommendations based on the CHADS(2) score, and the 2010 European Society of Cardiology guidelines were used to determine anticoagulation recommendations based on the CHA(2)DS(2)-VASc score.. The average age was 62±13 years, and 34% were women. Average CHADS(2) and CHA(2)DS(2)-VASc scores were 1.1±1.1 and 1.8±1.5, respectively (P<.0001). The CHADS(2) score classified 33% as requiring oral anticoagulation. The CHA(2)DS(2)-VASc score classified 53% as requiring oral anticoagulation. For women, 31% had a CHADS(2) score ≥ 2, but 81% had a CHA(2)DS(2)-VASc score ≥ 2 (P = .0001). Also, 32% of women with a CHADS(2) score of zero had a CHA(2)DS(2)-VASc score ≥ 2. For men, 25% had a CHADS(2) score ≥ 2, but 39% had a CHA(2)DS(2)-VASc score ≥ 2 (P<.0001).. Compared with the CHADS(2) score, the CHA(2)DS(2)-VASc score more clearly defines anticoagulation recommendations. Many patients, particularly older women, are redistributed from the low- to high-risk categories.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Complications; Drug Administration Schedule; Europe; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Male; Middle Aged; Practice Guidelines as Topic; Predictive Value of Tests; Primary Prevention; Propensity Score; Risk Assessment; Risk Factors; Secondary Prevention; Sex Factors; Societies, Medical; Stroke; United States; Warfarin

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Male; Platelet Aggregation Inhibitors; 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

Upper extremity deep vein thrombosis (DVT) has become a common occurrence nowadays due to emergence of multiple newer risk factors, such as implantation of permanent pacemaker (PPM) and implantable cardioverter-defibrillators. We are reporting 20 cases of upper extremity DVT related to PPM implantation.. All the patients presented within 6 months, with unilateral upper extremity swelling (90%), pain (45%), erythema (15%), and other less frequent features. Venography established the diagnosis in all the cases. Considering the distribution of possible risk factors of venous thrombosis among our patients, diabetes was the most frequent (present in 45%) followed by smoking (35%), hypertension (30%), obesity with body mass index ≥30 (30%), history of acute myocardial infarction (25%), chronic obstructive pulmonary disease (20%), and history of congestive cardiac failure (15%). Antiplatelets were not found protective against the development of this situation. There was no statistically significant difference in respect to venous access, number of leads, use of previous temporary pacing lead, or poor left ventricular systolic function (ejection fraction ≤40%) among the six patients who presented with complete occlusion of subclavian vein compared to the rest of the 14 patients who had partial occlusion. There were complete resolutions of symptom in 85% of patients after 6 months of anticoagulation therapy in the form of initial intravenous unfractinated heparin followed by oral warfarin.. Anticoagulation with warfarin for 6 months with initial intravenous unfractionated heparin was a safe and effective mode of therapy in most of the patients with PPM related upper extremity DVT.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Defibrillators, Implantable; Female; Heart Failure; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Pacemaker, Artificial; Radiography; Risk Factors; Severity of Illness Index; Stroke Volume; Subclavian Vein; Treatment Outcome; Upper Extremity Deep Vein Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Male; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Humans; Male; Platelet Aggregation Inhibitors; Warfarin

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Heart-Assist Devices; Humans; International Normalized Ratio; Male; Middle Aged; Thrombosis; Warfarin

Topics: Adenoma; Adenomatous Polyps; Anticoagulants; Aspirin; Coffee; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Female; Heart Failure; Humans; Male; Mortality; Platelet Aggregation Inhibitors; Warfarin

Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important.. From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported.. Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes.. Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Diabetes Complications; Female; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Male; Risk Assessment; Stroke; Ticlopidine; Treatment Outcome; Warfarin

Warfarin use and associated outcomes in patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device have not been described previously.. We hypothesized that warfarin is underused and is associated with lower risks of mortality, thromboembolic events, and myocardial infarction.. Using data from a clinical registry linked with Medicare claims, we examined warfarin use at discharge and 30-day and 1-year Kaplan-Meier estimates of all-cause mortality and cumulative incidence rates of mortality, thromboembolic events, myocardial infarction, and bleeding events in patients 65 years or older, with a history of atrial fibrillation and a cardiovascular implantable electronic device admitted with heart failure between 2001 and 2006, who were naïve to anticoagulation therapy at admission. We compared outcomes between patients who were or were not prescribed warfarin at discharge and tested associations between treatment and outcomes.. Of 2586 eligible patients in 252 hospitals, 2049 were discharged without a prescription for warfarin. At 1 year, the group discharged without warfarin had a higher mortality rate after discharge (37.4% vs 28.8%; P < 0.001) but similar rates of thromboembolism, myocardial infarction, and bleeding events. After adjustment, treatment with warfarin was associated with lower risk of all-cause death 1 year after discharge (hazard ratio: 0.76, 95% confidence interval: 0.63-0.92).. Among older patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device, 4 of 5 were discharged without a prescription for warfarin. Warfarin nonuse was associated with a higher risk of death 1 year after discharge. Clin. Cardiol. 2011 DOI: 10.1002/clc.22064 Damon M. Seils, MA, Duke University, assisted with manuscript preparation. Mr. Seils did not receive compensation for his assistance apart from his employment at the institution where the study was conducted. This study was supported by a research agreement between Duke University and Janssen Pharmaceuticals. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiac Pacing, Artificial; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Chi-Square Distribution; Defibrillators, Implantable; Electric Countershock; Female; Heart Failure; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Medicare; Myocardial Infarction; Pacemaker, Artificial; Patient Discharge; Proportional Hazards Models; Registries; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; United States; Warfarin

Chronic heart failure (HF) with either reduced or preserved left ventricular (LV) ejection fraction is common and remains an extremely serious disorder with a high mortality and morbidity. Many complications related to heart failure can be related to thrombosis. Epidemiological and pathophysiological data also link HF to an increased risk of thrombosis, leading to the clinical consequences of sudden death, stroke, systemic thromboembolism and/or venous thromboembolism. This executive summary of a joint consensus document of the Heart Failure Association (EHFA) of the European Society of Cardiology (ESC) and the ESC Working Group on Thrombosis reviews the published evidence, summarises 'best practice', and puts forward consensus statements that may help to define evidence gaps and assist management decisions in everyday clinical practice. In HF patients with atrial fibrillation, oral anticoagulation is clearly recommended, and the CHA2DS2-VASc and HAS-BLED scores should be used to determine the likely risk-benefit ratio (thromboembolism prevention versus risk of bleeding) of oral anticoagulation. In HF patients with reduced LV ejection fraction who are in sinus rhythm there is no evidence of an overall benefit of vitamin K antagonists (e.g. warfarin) on mortality, with risk of major bleeding. Whilst there is the potential for a reduction in ischaemic stroke, there is currently no compelling reason to routinely use warfarin for these patients. Risk factors associated with increased risk of thromboembolic events should be identified and decisions regarding use of anticoagulation individualised. Patient values and preferences are important determinants when balancing the risk of thromboembolism against bleeding risk. Novel oral anticoagulants that offer a different risk-benefit profile compared with warfarin may appear as an attractive therapeutic option, but this would need to be confirmed in clinical trials.

Topics: Anticoagulants; Aspirin; Case-Control Studies; Coronary Thrombosis; Europe; Fibrinolytic Agents; Heart Failure; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Societies, Medical; Stroke; Thromboembolism; Ventricular Dysfunction, Left; Warfarin

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

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

Topics: Anticoagulants; Evidence-Based Medicine; Heart Failure; Humans; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Warfarin

Topics: Aged; Alcohol Withdrawal Delirium; Anticoagulants; Aortic Aneurysm; Aortic Dissection; Aortic Valve Insufficiency; Atrial Fibrillation; Delayed Diagnosis; Diagnostic Errors; Dyspnea; Edema; Epilepsy, Tonic-Clonic; Fatal Outcome; Heart Failure; Heart Valve Prosthesis; Humans; Hypertension; Male; Postoperative Complications; Psychomotor Agitation; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Blood Coagulation; Drug Administration Schedule; Female; Heart Failure; Heart-Assist Devices; Hemorrhage; Humans; International Normalized Ratio; Male; Michigan; Middle Aged; Pilot Projects; Prosthesis Design; Retrospective Studies; Thromboembolism; Time Factors; Treatment Outcome; Ventricular Function, Left; Warfarin

Topics: Anticoagulants; Aspirin; Clopidogrel; Electrodes, Implanted; Equipment Design; Female; Heart Failure; Hemodynamics; Humans; Male; Microchip Analytical Procedures; Monitoring, Physiologic; Pulmonary Artery; Pulmonary Wedge Pressure; Sensitivity and Specificity; Survival Analysis; Ticlopidine; Warfarin

Thromboembolic events have been observed in heart failure (HF) patients supported by long-term mechanical circulatory support (MCS) devices. It has been hypothesized that these adverse events may be the result of platelet activation associated with high rotational speeds common to axial flow pumps. In this study, markers of platelet activation were investigated in HF patients supported by a HeartMate II left ventricular assist device (LVAD).. The study group consisted of 34 HF patients supported by a HeartMate II axial flow LVAD implanted for destination therapy (DT). This patient population was 94% male (31 M, 3 F), supported by LVAD for 30 to 723 days (average 268 days), and with an anticoagulation regimen of Coumadin (0-8 mg daily dose) and aspirin (0-325 mg daily dose). Platelet adhesion markers (soluble P-selectin and solube CD40 ligand), platelet count (PC), hematocrit (Hct), and creatinine (Cr) were measured.. The soluble P-selectin marker was within normal platelet activity limits for all end points. The soluble CD40 ligand marker indicated platelet inactivity for all end points. Despite high shear stresses associated with a high-speed axial flow pump, the HeartMate II had no discernable effect on platelet activation. Current clinical doses of aspirin also appear to have little effect on platelet activation. Platelet count, hematocrit, and creatinine were normal in these patients over duration of support.. There were no discernable changes in platelet activation markers soluble P-selectin and soluble CD40 ligand in HF patients support by HeartMate II LVAD independently of length of support, anti-platelet, and anti-coagulation regimens.

Topics: Aged; Anticoagulants; Aspirin; Biomarkers; CD40 Ligand; Creatinine; Cross-Sectional Studies; Female; Heart Failure; Heart-Assist Devices; Hematocrit; Hemolysis; Humans; Illinois; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Prosthesis Design; Time Factors; Treatment Outcome; Warfarin

Almost 50% of patients with congestive heart failure (HF) have preserved ejection fraction (PEF). Data on the effect of HF-PEF on atrial fibrillation outcomes are lacking. We assessed the prognostic significance of HF-PEF in an atrial fibrillation population compared to a systolic heart failure (SHF) population. A post hoc analysis of the National Heart, Lung, and Blood Institute-limited access data set of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was carried out. The patients with a history of congestive HF and a preserved ejection fraction (EF >50%) were classified as having HF-PEF (n = 320). The patients with congestive HF and a qualitatively depressed EF (EF <50%) were classified as having SHF (n = 402). Cox proportional hazards analysis was performed. The mean follow-up duration was 1,181 ± 534 days/patient. The patients with HF-PEF had lower all-cause mortality (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46 to 0.85, p = 0.003) and cardiovascular mortality (HR 0.56, 95% CI 0.38 to 0.84, p = 0.006), with a possible decreased arrhythmic end point (HR 0.39, 95% CI 0.16 to 1.006, p = 0.052) than did the patients with SHF. No differences were observed for ischemic stroke (HR 1.08, 95% CI 0.48 to 2.39, p = 0.86), rehospitalization (HR 0.89, 95% CI 0.75 to 1.07, p = 0.24), or progression to New York Heart Association class III-IV (odds ratio 0.80, 95% CI 0.42 to 1.54, p = 0.522). In conclusion, although patients with HF-PEF have better mortality outcomes than those with SHF, the morbidity appears to be similar.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Disease Progression; Female; Heart Failure; Humans; Hypertension; Male; Patient Readmission; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Sex Factors; Stroke; Stroke Volume; United States; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Heart Failure; Hemorrhage; Humans; Patient Selection; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

Previous studies have not confirmed associations between some current performance measures for inpatient heart failure processes of care and postdischarge outcomes. It is unknown if alternative measures are associated with outcomes.. Using data for 20,441 Medicare beneficiaries in OPTIMIZE-HF from March 2003 through December 2004, which we linked to Medicare claims data, we examined associations between hospital-level processes of care and patient outcomes. Performance measures included any beta-blocker for patients with left ventricular systolic dysfunction (LVSD); evidence-based beta-blocker for patients with LVSD; warfarin for patients with atrial fibrillation; aldosterone antagonist for patients with LVSD; implantable cardioverter-defibrillator for patients with ejection fraction < or =35%; and referral to disease management. Outcome measures were unadjusted and adjusted associations of each process measure with 60-day and 1-year mortality and cardiovascular readmission at the hospital level.. Adjusted hazard ratios for 1-year mortality with a 10% increase in hospital- level adherence were 0.94 for any beta-blocker (95% CI, 0.90-0.98; P = .004), 0.95 for evidence-based beta-blocker (95% CI, 0.92-0.98; P = .004); 0.97 for warfarin (95% CI, 0.92-1.03; P = .33); 0.94 for aldosterone antagonists (95% CI, 0.91-0.98; P = .006); 0.92 for implantable cardioverter-defibrillator (95% CI, 0.87-0.98; P = .007); and 1.01 for referral to disease management (95% CI, 0.99-1.03; P = .21).. Several evidence-based processes of care are associated with improved outcomes, can discriminate hospital-level quality of care, and could be considered as clinical performance measures.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Evidence-Based Medicine; Female; Heart Failure; Hospitalization; Humans; Male; Medicare; Mineralocorticoid Receptor Antagonists; Patient Readmission; Proportional Hazards Models; Quality of Health Care; Registries; Survival Analysis; Treatment Outcome; United States; Ventricular Dysfunction, Left; Warfarin

Some studies have suggested that heart failure (HF) is associated with excessive anticoagulation, but definitive data or data showing causation do not exist. Knowledge of risk factors for excessive anticoagulation is critical to manage warfarin therapy safely.. This study characterized the relation between HF-associated hypervolemia and excessive anticoagulation in patients with HF taking chronic warfarin therapy.. This was a prospective, observational pilot study conducted in a university-based HF clinic. Patients aged 18 to 85 years with HF and taking warfarin were enrolled and were observed for episodes of hypervolemia. Hypervolemia was determined based on multiple clinical factors, including patient-reported symptoms and physical examination. Anticoagulation was assessed longitudinally per standard of care by measurement of the international normalized ratio (INR). A chi(2) analysis was used to determine whether hypervolemia was associated with an increased risk of excessive anticoagulation. Paired and unpaired t tests were used for ad hoc analyses.. Forty patients with 41 HF episodes who were taking warfarin were enrolled between December 2003 and July 2007. Mean (SD) age was 67.2 (11.1) years and mean weight was 218.5 (62.8) pounds; 29 patients (72.5%) were men and 34 (85.0%) were white. Most had systolic dysfunction (n = 26; 65.0%) and were taking warfarin for atrial fibrillation (n = 33; 82.5%); the mean weekly warfarin dose was 30.8 (17.5) mg. There were 41 evaluable hypervolemia episodes over a mean follow-up of 14.5 (9.0) months. The mean INR change during hypervolemia was -0.02 (0.82) INR unit (P = NS vs baseline). No association was found between hypervolemia episodes and INR increases of > or =50% (P = NS); the results remained nonsignificant for both diastolic and systolic HF when analyzed separately. There was no significant change from baseline INR between patients classified with mild, moderate, or severe hypervolemia or between patients classified according to New York Heart Association (NYHA) functional class (all, P = NS). Patients with NYHA class III had a lower weekly warfarin dose than those with NYHA class II (25.73 vs 31.75 mg; P < 0.01).. Mild hypervolemia did not appear to be related to excessive anticoagulation in these patients with HF taking chronic warfarin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Volume; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Pilot Projects; Prospective Studies; Risk Factors; Severity of Illness Index; Warfarin

Anti-coagulation with heparin is often used after left ventricular assist device implantation as a transition to long-term warfarin therapy. We retrospectively evaluated the effects of heparin use on thromboembolic and bleeding complications after implantation of the HeartMate II left ventricular assist device (LVAD).. LVAD patients (n = 418) implanted as a bridge to transplant were divided into three groups: Group A patients (therapeutic, n = 118) received heparin and had a partial thromboplastin time (PTT) of >50 seconds on two or more occasions; Group B patients (sub-therapeutic, n = 178) had at least one PTT value in the range of 40 to 55 seconds; and Group C patients (no heparin, n = 122) had no PTT values >40 seconds. All patients were transitioned to warfarin and aspirin therapy. The following adverse events were evaluated: ischemic stroke; hemorrhagic stroke; pump thrombosis; bleeding requiring surgery; and bleeding requiring > or = 2 units of packed red blood cells in 24 hours.. There was no difference in the percentages of patients with ischemic (5%, 4%, 3%) or hemorrhagic (3%, 3%, 5%) strokes or pump thrombosis (3%, 2%, 2%) after post-operative day (POD) 3 among Groups A, B and C, respectively. From PODs 3 to 30, the percentage of patients requiring transfusion for bleeding was significantly lower for Group C (18%) than for Groups A (32%) and B (26%) (p = 0.04); differences after 30 days were not significant. Multivariate analysis revealed that post-operative heparin use, low post-operative platelet count and low baseline hematocrit value were independent risk factors for bleeding events between PODs 3 and 30.. In patients receiving the HeartMate II LVAD who were directly transitioned to warfarin and aspirin therapy without intravenous heparin there was no short-term increase in risk of thrombotic or thromboembolic events, and bleeding requiring transfusion was significantly reduced. Additional long-term follow-up is needed to evaluate possible late effects.

Topics: Anticoagulants; Aspirin; Drug Administration Schedule; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hemorrhage; Heparin; Humans; Injections, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Postoperative Care; Postoperative Complications; Postoperative Period; Retrospective Studies; Stroke; Thromboembolism; Thrombosis; Time Factors; Unnecessary Procedures; Warfarin

Heart failure is a significant public health problem. The present study is intended to explore in a research database whether antithrombotic therapies (ATTs) affect cardiovascular outcomes in patients with incident heart failure (IHF).. Using the United Kingdom Health Improvement Network research database, several multivariable models (including logistic and Cox's regression models, as well as propensity score methods) were used to examine all-cause mortality and clinical outcomes among five treatment groups.. The cohort included 24,554 patients with IHF (50.2% men), with a mean age (standard deviation [SD]) of 76.4 (11.0) years. Nearly three-fourths of patients received at least one form of ATT. Patients receiving ATTs tended to be younger and more likely to be men, and had more cardiovascular comorbidities. During the 18-month follow-up period, the mortality rates were 11.1%, 14.6%, 17.8%, 19.5%, and 32.6% for warfarin combination therapy, warfarin alone, clopidogrel therapy, aspirin (ASA) alone, and no therapy, respectively, yielding odds ratios (95%confidence intervals [CI]) relative to no therapy of 0.28 (0.24, 0.33), 0.38 (0.34, 0.43), 0.46 (0.40, 0.52), and 0.49 (0.45, 0.53) for each therapy group, accordingly. The use of ATTs also appeared to be associated with a reduced risk for ischemic or thrombotic events.. These data contribute to the formulation of the hypothesis that use of ATTs in clinical practice decreases the risk of morbidity and mortality in patients with IHF, although findings require further confirmative studies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Databases, Factual; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Sex Factors; Ticlopidine; United Kingdom; Warfarin; Young Adult

A cardiac thrombus provides a substrate for thromboembolic events. Delayed enhancement cardiac magnetic resonance imaging detects a thrombus based on avascular tissue properties, and has been shown to provide improved detection of a left ventricular thrombus, compared with anatomic imaging using echocardiography. We present a case of a young man with cerebrovascular stroke in whom delayed enhancement cardiac magnetic resonance provided incremental diagnostic utility for identification of a thrombus within both the left-sided and right-sided cardiac chambers.

Topics: Adult; Anticoagulants; Coronary Thrombosis; Diagnosis, Differential; Follow-Up Studies; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Male; Stroke; Warfarin; Young Adult

Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels.. We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls.. We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS.. We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis.. A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aorta; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Blood Pressure; Calcinosis; Calcium-Binding Proteins; Cause of Death; Echocardiography; Extracellular Matrix Proteins; Female; Heart Failure; Humans; Male; Matrix Gla Protein; Middle Aged; Prognosis; Warfarin

Topics: Aspirin; Atrial Fibrillation; Cardiomegaly; Dyspnea; Echocardiography; Embolization, Therapeutic; Heart Failure; Heparin; Humans; Male; Middle Aged; Stroke Volume; Warfarin

In patients on high-level anticoagulant therapy (prothrombin time-international normalized ratio [PT-INR] ≥ 4.5), surgical procedures can be carried out with bridging therapy using heparin. However, surgical treatment options are severely limited in patients on high-level anticoagulant therapy and who have heparin-induced thrombocytopenia (HIT), as heparin use is contraindicated. We performed tooth extraction using prothrombin complex concentrate (PCC) in 2 HIT patients on high-level anticoagulation therapy (PT-INR ≥ 4.5). Five hundred units of PCC were administered intravenously, and after 15 minutes, it was confirmed that PT-INR was less than 2.0. Tooth extraction was then performed and sufficient local hemostasis was achieved. At 3 hours after tooth extraction, PT-INR was 2.0 or higher and later increased to 4.0 or higher, but postoperative bleeding was mostly absent. When performing tooth extraction in HIT patients on high-level anticoagulant therapy, favorable hemostatic management was achieved through sufficient local hemostasis and transient warfarin reversal using PCC.

Topics: Adult; Aspirin; Blood Coagulation Factors; Blood Loss, Surgical; Cellulose, Oxidized; Contraindications; Electrocoagulation; Female; Fibrinolytic Agents; Gingival Hemorrhage; Heart Failure; Heart-Assist Devices; Hematoma; Hemostatics; Heparin; Humans; International Normalized Ratio; Male; Molar, Third; Periapical Periodontitis; Pericoronitis; Plasma; Postoperative Hemorrhage; Prothrombin Time; Thrombosis; Tooth Extraction; Tooth, Impacted; Warfarin

A case to illustrate the utility of genetic screening in warfarin (Coumadin) management is reported. A 45 year-old woman of Puerto Rican ancestry was admitted to the emergency room twice within one month with chest pain. She was diagnosed with congestive heart failure, which was stabilized both times. At her second release, warfarin therapy was initiated at 5 mg/ day to prevent thrombus formation and was lowered to 3.75 mg/day at day 7 by her primary physician. International Normalized Ratio (INR) test results in the follow-up period at days 1, 7, and 10 of warfarin therapy were 4.5, 6.5, and 7.3, respectively-far in excess of the therapeutic range, despite the lower dosage in effect from day 7 onward. The patient achieved target INR over the next 43 days after downward adjustment of the dose to a dose of 1.5 mg/day by trial and error. DNA-typing specific for the CYP2C9*2,*3,*4,*5,*6 alleles and seven variants in the VKORC1 gene, including the VKORC1-1639 G > A polymorphism, revealed the presence of combinatorial CYP2C9*2/*3 and VKORC1-1639 G/A genotypes in this patient. Entering the patient's demographic and genotype status data into independent algorithms available in the public domain to predict effective warfarin dose yielded predicted doses which ranged from 1.5 to 1.8 mg/day. Notably, the prediction of 1.5 mg/day, which was generated by the online resource www.warfarindosing.org, coincided with the patient's actual effective warfarin dose. We conclude that the rapid rise in INR observed upon the initiation of warfarin therapy and the final effective warfarin dose of 1.5 mg/day, are attributable in some part to the presence of two minor alleles in CYP2C9, which together significantly reduce warfarin metabolism. Warfarin genotyping can therefore inform the clinician of the predicted effective warfarin dose. The results highlight the potential for warfarin genetic testing to improve patient care.

Topics: Anticoagulants; Female; Genotype; Heart Failure; Humans; International Normalized Ratio; Middle Aged; Risk Factors; Warfarin

Topics: Anticoagulants; Bundle-Branch Block; Contrast Media; Defibrillators, Implantable; Diagnosis, Differential; Echocardiography; Electrocardiography; Heart Failure; Humans; Male; Middle Aged; Ventricular Dysfunction, Left; Warfarin

For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cohort Studies; Colorado; Comorbidity; Diabetes Mellitus; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Evidence-Based Medicine; Female; Heart Failure; Humans; Male; Meta-Analysis as Topic; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke; Stroke Volume; Thrombophilia; Ventricular Function, Left; Warfarin

A warfarin treated patient unexpectedly presented with an elevated international normalized ratio (INR). Repeat testing in two laboratories gave conflicting results. The chromogenic assay of factor X was used to determine the correct INR result. The patient had laboratory results consistent with a dysfibrinogenemia, which prevented detection of the endpoint with a photo-optical detection system. The chromogenic assay of factor X is recommended for monitoring patients on warfarin when the INR cannot be accurately determined due to interference with the fibrin endpoint in the INR.

Topics: Aged; Anticoagulants; Blood Coagulation; Chromogenic Compounds; Factor X; Female; Fibrin; Fibrinogen; Heart Failure; Humans; International Normalized Ratio; Lung Neoplasms; Prothrombin Time; Time Factors; Warfarin

This study sought to examine quality of care and warfarin use at discharge in patients with atrial fibrillation (AF) and heart failure (HF).. Atrial fibrillation is common in HF, and national guidelines recommend discharge on warfarin for stroke prophylaxis. However, the frequency and factors associated with the guideline adherence are poorly described.. We analyzed 72,534 HF admissions from January 2005 through March 2008 at 255 hospitals participating in the American Heart Association's Get With The Guidelines HF program. Multivariable logistic regression was used to identify independent factors associated with warfarin use at discharge.. In this HF population, 20.5% (n=14,901) had AF on admission, whereas another 13.7% (n=9,918) had a prior history of AF but were in a regular rhythm at admission. Contraindications to warfarin therapy were documented in 9.2%. Among eligible HF patients without contraindications, the median prevalence of warfarin therapy at discharge was 64.9% (interquartile range 55.5 to 73.4) and did not improve during the 3.5 years of study. After adjustment, major factors associated with no warfarin use at discharge included increasing age, nonwhite race, anemia, and treatment in the south. Warfarin use also varied inversely with CHADS2 (congestive heart failure, hypertension, age>75, diabetes, and prior stroke or transient ischemic attack) risk (70.9% to 59.5% for CHADS2 score 1 to 6, p<0.0001).. Guideline-recommended warfarin use in patients with AF and HF is less than optimal, has not improved over time, and varies significantly according to age, race, risk profile, region, and hospital site.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Drug Utilization; Female; Guideline Adherence; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Patient Discharge; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prospective Studies; Quality of Health Care; Racial Groups; Registries; Residence Characteristics; Risk Assessment; Stroke; United States; 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

The antiphospholipid syndrome is characterized by arterial and venous thrombosis and is associated with the presence of circulating antiphospholipid antibodies. Arterial thrombosis can result in myocardial infarction, which may potentially lead to end-stage heart failure. Here we report our anticoagulation protocol for patients with antiphospholipid syndrome that undergo axial-flow left ventricle assist devices (HeartMate II; Thoratec, Pleasanton, CA) implantation.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Antigens, CD20; Antiphospholipid Syndrome; Heart Failure; Heart-Assist Devices; Heparin; Humans; Male; Plasma Exchange; Plasmapheresis; Preoperative Care; Prosthesis Implantation; Rituximab; Warfarin

We report a case of a 57-year-old patient with a history of a Starr-Edwards mitral valve prosthesis and DeBakey-Surgitool aortic valve prosthesis implanted 30 years ago who presented with symptoms consistent with class IV heart failure. The patient had been on no anticoagulation for approximately 30 years secondary to recurrent epistaxis occurring two years after starting warfarin therapy postoperatively. Throughout the patient's lifetime he experienced no thromboembolic complications from the lack of anticoagulation, despite developing concomitant atrial fibrillation approximately ten years prior to admission. In place of warfarin the patient had substituted large doses of aspirin. A workup revealed normal function of the mechanical valves for this extensive period.

Topics: Anticoagulants; Aortic Valve; Aspirin; Atrial Fibrillation; Endocarditis, Bacterial; Epistaxis; Heart Failure; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve; Platelet Aggregation Inhibitors; Prosthesis Design; Self Medication; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Coronary Thrombosis; Cough; Cytochrome P-450 CYP2C9; Genotype; Heart Failure; Humans; International Normalized Ratio; Losartan; Male; Middle Aged; Pharmacogenetics; Polypharmacy; Ramipril; Warfarin

Patients with mechanical heart valves require anticoagulation which is associated with significant maternal mortality (1-4%) and fetal complications (31%) in pregnancy. The study aim was to identify anticoagulant protocols and outcomes for pregnant women undergoing heart valve replacement (HVR) in the United Kingdom.. Women aged between 18 and 45 years and registered with the United Kingdom Heart Valve Registry (UKHVR) each completed a questionnaire, and their obstetric notes were reviewed. The data analyzed included valve type (mechanical, bioprosthetic, homograft), valve site (mitral, aortic, tricuspid, pulmonary), anticoagulation at confirmation of pregnancy, between 6-12 weeks and from 12 weeks to term, delivery, maternal and fetal outcomes, and cause of death. The summary statistics and a descriptive review of the findings are reported.. Of 2,532 women eligible for the study, 922 responded. Among these women, 72 became pregnant, with 60 pregnancies in the mechanical valve (MV) group and 45 in the tissue valve (TV) group. Three anticoagulation regimes were used during early pregnancy: unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or warfarin. All women received warfarin in the second trimester and heparin for delivery. Live births were recorded in 30% of MV pregnancies and in 60% of TV pregnancies. Miscarriage rates differed markedly (37% MV versus 2% TV). Fetal outcome was poorest in the warfarin-only group, with embryopathy occurring at a dose level of 6 mg. The maternal outcomes did not differ significantly among groups. High-dose heparin during the first trimester and for delivery was effective for the majority of mechanical valves.. The study results illustrate the diverse and uncertain manner in which UKHVR patients are managed during pregnancy. A national notification system would record much-needed prospective information on anticoagulation and pregnancy outcomes, thus aiding evidence-based management.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anticoagulants; Bioprosthesis; Cause of Death; Dose-Response Relationship, Drug; Female; Fetal Diseases; Heart Failure; Heart Valve Prosthesis Implantation; Heparin; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors; United Kingdom; Warfarin

Topics: Anticoagulants; Aortic Valve; Aspirin; Atrial Fibrillation; Endocarditis, Bacterial; Epistaxis; Heart Failure; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Platelet Aggregation Inhibitors; Prosthesis Design; Self Medication; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Adherence to heart failure therapy is important in reducing morbidity and mortality over the course of the disease process. The aim of this study was to examine factors associated with non-adherence to warfarin in chronic heart failure patients.. Eighty patients receiving warfarin therapy in 2002 were included. Adherence was defined as maintenance of international normalized ratio (INR) between 2 and 3.5 and keeping scheduled appointments for INR checks at least 75% of the time. Clinical variables examined included age, gender, race, insurance, left ventricular ejection fraction (LVEF), etiology, New York heart association (NYHA) class, comorbidities, smoking, and alcohol use.. Of 80 patients studied, 59 were male with mean age ( +/- standard deviation) 52 +/- 13 years, 24 had ischemic etiology with mean LVEF of 24% +/- 9%. Non-adherence was associated with tobacco use, odds ratio of 6.5 (p <0.01). Ischemic etiology was associated with adherence, odds ratio of 4.5 (p <0.01). Non-adherent patients were more likely to be insured with Medicare/Medicaid (p = 0.04) and have better NYHA class (p = 0.04). Adherence positively correlated with older age and lower LVEF, and negatively correlated with number of hospitalizations (p<0.01 for all). In a multiple regression model, patients with improvement in LVEF had decreased adherence over the year (p<0.01).. The profile of heart failure patients who demonstrated non-adherence to warfarin therapy included younger age, nonischemic etiology, better NYHA class, smoking, insurance with Medicare/Medicaid and improved LVEF over the study. Measures targeting these patients may result in improved adherence to other pharmacologic treatments of heart failure.

Topics: Anticoagulants; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Morbidity; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Treatment Refusal; United States; Warfarin

We report successful surgical management of a 31-year-old man with a left ventricular thrombus following heart failure due to cardiac sarcoidosis. Preoperative echocardiography showed diffuse hypokinesis and a mobile ball-like thrombus in the left ventricle. Computed tomography revealed a left ventricular tumor and bilateral hilar lymphadenopathy, while MRI of the brain showed small infarctions in the occipital lobe. Postoperative pathologic examination of a specimen from the left ventricular free wall and a mediastinal lymph node revealed non-caseating granulomas consistent with cardiac sarcoidosis. The patient was referred to a cardiologist for further treatment with prednisolone. This is a rare case of surgical removal of a left ventricular ball-like thrombus in a patient with cardiac sarcoidosis.

Topics: Adult; Anticoagulants; Cardiomyopathies; Cerebral Infarction; Glucocorticoids; Heart Diseases; Heart Failure; Heart Ventricles; Humans; Lymphatic Diseases; Magnetic Resonance Imaging; Male; Occipital Lobe; Prednisolone; Sarcoidosis; Thrombectomy; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Clopidogrel; Drug Interactions; Heart Failure; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Thromboembolism; Ticlopidine; Warfarin

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; 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

We experienced two cases of heparin-induced thrombocytopenia (HIT) which occurred during unfractionated heparin treatment. The first patient was a 72-year-old man, who was admitted to our hospital because of sudden onset dyspnea in January 2000. He was diagnosed as having a pulmonary embolism and heparin was started. Nine days later, progressive embolization of the pulmonary artery and femoral vein was found and thrombocytopenia (platelet count 20 x 10(9)/l) was observed 14 days after that. Cessation of heparin and administration of argatroban resulted in progressive normalization of the platelet count. The second patient was a 62-year-old woman, who was admitted to our hospital in April 2001, with the chief complaint of sudden onset dyspnea. She was diagnosed as having acute left-sided heart failure and heparin was started. Fifteen 15 days later, thrombocytopenia (platelet count 17 x 10(9)/l) was observed. Cessation of heparin resulted in normalization of the platelet count. Both cases were positive for anti-heparin-platelet factor 4 (PF4) antibody. Here we report on the clinical course of two cases of HIT with a review of the literature.

Topics: Aged; Antibodies; Arginine; Female; Heart Failure; Heparin; Humans; Male; Middle Aged; Pipecolic Acids; Platelet Factor 4; Pulmonary Embolism; Sulfonamides; Thrombocytopenia; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Heart Failure; Humans; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

In 1,009 patients with atrial fibrillation and congestive heart failure, the 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Chi-Square Distribution; Digoxin; Female; Heart Failure; Humans; Male; Proportional Hazards Models; Statistics, Nonparametric; Treatment Outcome; Warfarin

The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF over the observation period: aspirin use increased from 14% to 39% in men and from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and from 17% to 38% in women. There were no significant gender differences in anticoagulant use (p = 0.61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Heart Failure; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prevalence; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Warfarin

Uhl's anomaly, or parchment right ventricle is a myocardial disorder of unknown cause that mainly involves the right ventricle. Uhl's anomaly may represent a cause of right heart dilatation, failure, and premature sudden death due to ventricular arrhythmias. Although most of the cases of Uhl's anomaly end fatally in infancy or childhood, a limited number of cases have been reported in advanced ages. Also, in pregnant women, this situation increases the risk to both mother and baby and requires special management. This is the first report of six successful consecutive gestations and vaginal deliveries without special managements in a patient with Uhl's anomaly.

Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Furosemide; Gestational Age; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Parity; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Ventricular Dysfunction, Right; Warfarin

To evaluate recent trends, we examined longitudinal national data on the outpatient use of warfarin in atrial fibrillation (AF), beta-blockers and aspirin in coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors (ACEIs) in congestive heart failure (CHF).. Previous studies indicate that specific cardiac medications are underutilized.. We used the National Disease and Therapeutic Index (NDTI) (produced by IMS HEALTH, Plymouth Meeting, Pennsylvania) for 1990 to 2002, and the National Ambulatory Medical Care Surveys (NAMCS) for 1990 to 2000 to follow nationally representative samples of outpatient visits. For visits by patients with AF (total n = 14,634 visits), CAD (n = 35,295), and CHF (n = 33,008), we examined trends in the proportion of visits with the selected medications reported.. Warfarin use in AF increased from 12% in 1990, to 41% in 1995, to 58% in 2001 in NDTI; a similar moderation of recent increase was seen in NAMCS. For CAD in NDTI, beta-blocker use increased slowly from 19% in 1990, to 20% in 1995, then to 40% in 2001; NAMCS showed this same pattern. Aspirin use in CAD in NDTI increased from 18% in 1990, to 19% in 1995, to 38% in 2001; NAMCS, however, showed lower use rates. For NDTI, ACEI use in CHF increased from 24% in 1990 to 36% in 1996, but increased to only 39% by 2001, a general pattern also seen in NAMCS.. Both national datasets demonstrate continuing underutilization of these cardiac medications of proven benefit. Although use is increasing, it remains lower than expected, and some increases noted in earlier years have slowed. Substantial public health benefits would result from further adoption of these effective therapies.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Atrial Fibrillation; Cardiovascular Agents; Coronary Artery Disease; Drug Therapy; Drug Utilization; Health Care Surveys; Heart Failure; Hematologic Agents; Humans; Longitudinal Studies; Office Visits; United States; Warfarin

Quality indicators are measurement tools for assessing the structure, processes and outcomes of care. Although quality indicators have been developed in other countries, Canadian cardiovascular disease indicators do not exist.. To develop quality indicators for measuring and improving congestive heart failure (CHF) care in Canada.. An 11-member multidisciplinary national expert panel was selected from nominees from national medical organizations. Potential quality indicators were identified by a detailed search of published guidelines, randomized trials and outcomes studies. A two-step modified Delphi process was employed with an initial screening round of indicator ratings, followed by a national quality indicator panel meeting, where definitions of the indicators were developed using consensus methods. Indicators were designed to be measurable, using retrospective chart review and linking existing administrative databases.. The case definition criterion was developed based on a discharge diagnosis of CHF (International Classification of Diseases, 9th revision [ICD-9] code 428.x), with diagnostic confirmation using clinical criteria. In total, 29 indicators and five test indicators were recommended. Process indicators included prescription for angiotensin-converting enzyme inhibitors, beta-blockers or warfarin (for atrial fibrillation) at hospital discharge. Nonpharmacological in hospital process indicators included evaluation of left ventricular function, weight measurement and selected patient education counselling instructions. Process indicators in the ambulatory setting included prescription and adherence to drug therapies and physician follow-up. Outcome indicators included mortality, readmissions and emergency visits.. A set of Canadian quality indicators for CHF care encompassing organizational attributes, pharmacotherapy, investigations, counselling, continuity of care and disease outcomes has been developed. These quality indicators will serve as a foundation for future studies evaluating the quality of CHF care in Canada.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Benchmarking; Canada; Delphi Technique; Health Services Research; Heart Failure; Hospitalization; Humans; International Classification of Diseases; National Health Programs; Outcome and Process Assessment, Health Care; Patient Education as Topic; Practice Patterns, Physicians'; Quality Indicators, Health Care; Ventricular Function, Left; Warfarin

Previous reports have suggested that internists employ evidence-based care for congestive heart failure (CHF) less frequently than cardiologists. Reasons for this possible difference are unclear.. A retrospective review of 185 consecutive patients admitted to a Canadian tertiary care facility between April 1998 and March 1999 with a primary diagnosis of CHF and who were treated by internists (IM group) or cardiologists (CARD group) was conducted.. The CARD group (n=65) was younger (70 versus 76 years, P<0.001) and had larger left ventricular end-diastolic diameter by echocardiography (57 versus 51 mm, P=0.006) than the IM group (n=120). The CARD group documented ejection fraction in 90% of cases versus 54% in the IM group (P<0.05). There was no difference in angiotensin-converting enzyme (ACE) inhibitor usage (68% versus 63%, P=0.48) or optimal ACE dosage (CARD 50% versus IM 42%, P=0.44). Multivariate predictors of ACE inhibitor usage were serum creatinine, male sex, peripheral edema and increasing serum glucose. The CARD group had higher usage of beta-blockers (69% versus 49%, P<0.009), lipid lowering medication (35% versus 17%, P<0.004) and warfarin therapy for atrial fibrillation (74% versus 28%, P<0.005).. The data suggest that Canadian cardiologists and internists use ACE inhibitors equally and care for a relatively similar group of CHF patients. However, beta-blockade, warfarin, lipid lowering therapy and documentation of critical data occurred more frequently under cardiologist care. The possibility that there may be a gradation of adoption of newer guidelines for CHF care according to physician specialty is raised.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiology; Female; Guideline Adherence; Heart Failure; Humans; Hypolipidemic Agents; Internal Medicine; Male; Medical Records; Nova Scotia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

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

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

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

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Decision Making; Ethics, Clinical; Heart Failure; Hemorrhage; Humans; Judgment; Risk Factors; Stroke; Warfarin; Withholding Treatment

Topics: Aged; Aged, 80 and over; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Heart Failure; Homozygote; Humans; Male; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Warfarin

Topics: Alleles; Anticoagulants; Cytochrome P-450 Enzyme System; Heart Failure; Homozygote; Humans; Steroid Hydroxylases; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Heart Failure; Heart Valve Prosthesis; Humans; International Normalized Ratio; Stroke; Thrombolytic Therapy; Warfarin

An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of patients with asymptomatic elevations in INR is hampered by the lack of understanding of the time course of INR decay after cessation of warfarin therapy.. To identify predictors of the rate of INR normalization after excessive anticoagulation.. Retrospective cohort study.. Outpatient anticoagulant therapy unit.. Outpatients with an INR greater than 6.0 were identified from August 1993 to September 1998. Patients in whom two doses of warfarin were withheld and a follow-up INR was obtained on the second calendar day were enrolled. No patient received vitamin K(1).. The INR was measured 2 days after an INR greater than 6.0 was recorded.. Of 633 study patients with an initial INR greater than 6.0, 232 (37%) still had an INR of 4.0 or greater after two doses of warfarin were withheld. Patients who required larger weekly maintenance doses of warfarin were less likely to have an INR of 4.0 or greater on day 2 (adjusted odds ratio per 10 mg of warfarin, 0.87 [95% CI, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per decade of life, 1.18 [CI, 1.01 to 1.38]), index INR (odds ratio per unit, 1.25 [CI, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [CI, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [CI, 1.11 to 5.57]).. Steady-state warfarin dose, advanced age, and extreme elevation in INR are risk factors for prolonged delay in return of the INR to within the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Half-Life; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cohort Studies; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Vitamin K 1; Warfarin

Topics: Anticoagulants; Cysts; Diabetes Mellitus, Type 2; Diagnosis, Differential; Echocardiography; Electrocardiography; Heart Failure; Heart Ventricles; Heparin; Humans; Male; Middle Aged; Thrombosis; Warfarin

Azithromycin is considered unlikely to interact with warfarin. Unlike other macrolide antibiotics, it is not hepatically metabolized and did not produce an interaction with warfarin in a single-dose study. A 71-year-old woman with a prosthetic heart valve, stabilized with warfarin, had international normalized ratios (INRs) maintained between 2.5 and 3.5. Six days after she received a prescription for a 5-day course of azithromycin, her INR was 15.16. Phytonadione 10 mg was administered subcutaneously, and warfarin was held for 3 days until her INR fell to 2.10. She then was restabilized with warfarin. Until more information is known about the safety of warfarin and azithromycin, caution is advised when the agents are given together. Close monitoring of INR is recommended, and warfarin dosage adjustment may be necessary.

Topics: Aged; Anti-Bacterial Agents; Anticoagulants; Azithromycin; Drug Interactions; Female; Heart Failure; Humans; International Normalized Ratio; Warfarin

It is not known whether quality of care for congestive heart failure (CHF) at rural hospitals is similar to that in larger, urban hospitals.. We reviewed hospital charts for 310 Medicare patients hospitalized with CHF at six hospitals in rural Georgia.. Of the 310 patients, 101 (33%) had left ventricular systolic dysfunction, and 60 (19%) had preserved systolic function. Information on left ventricular function was not available for 48% (range, 29% to 87% across the six hospitals). Among patients with systolic dysfunction, 77% were prescribed an angiotensin converting enzyme (ACE) inhibitor at discharge, and 73% were prescribed digoxin. However, the mean daily ACE inhibitor dose was only 48% of the recommended target dose. Only 30% of all patients with atrial fibrillation were prescribed warfarin.. Overall quality of care for CHF at rural hospitals appears similar to that in other settings, though many patients may not receive evaluation of ventricular function.

Topics: Aged; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiotonic Agents; Digoxin; Drug Utilization; Female; Georgia; Heart Failure; Hospitals, Rural; Humans; Male; Medical Records; Medicare; Quality of Health Care; Retrospective Studies; United States; Ventricular Dysfunction; Warfarin

Topics: Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Myocardial Infarction; Warfarin

To investigate the occurrence of heart failure complications, and to identify variables that predict heart failure in patients with (recurrent) persistent atrial fibrillation, treated aggressively with serial electrical cardioversion and antiarrhythmic drugs to maintain sinus rhythm.. Non-randomised controlled trial; cohort; case series; mean (SD) follow up duration 3.4 (1.6) years.. Tertiary care centre.. Consecutive sampling of 342 patients with persistent atrial fibrillation (defined as > 24 hours duration) considered eligible for electrical cardioversion.. Serial electrical cardioversions and serial antiarrhythmic drug treatment, after identification and treatment of underlying cardiovascular disease.. heart failure complications: development or progression of heart failure requiring the institution or addition of drug treatment, hospital admission, or death from heart failure.. Development or progression of heart failure occurred in 38 patients (11%), and 22 patients (6%) died from heart failure. These complications were related to the presence of coronary artery disease (p < 0.001, risk ratio 3.2, 95% confidence interval (CI) 1.6 to 6.5), rheumatic heart disease (p < 0.001, risk ratio 5.0, 95% CI 2.4 to 10.2), cardiomyopathy (p < 0.001, risk ratio 5.0, 95% CI 2.0 to 12.4), atrial fibrillation for < 3 months (p = 0.04, risk ratio 2.0, 95% CI 1.0 to 3.7), and poor exercise tolerance (New York Heart Association class III at inclusion, p < 0.001, risk ratio 3.5, 95% CI 1.9 to 6. 7). No heart failure complications were observed in patients with lone atrial fibrillation.. Aggressive serial electrical cardioversion does not prevent heart failure complications in patients with persistent atrial fibrillation. These complications are predominantly observed in patients with more severe underlying cardiovascular disease. Randomised comparison with rate control treatment is needed to define the optimal treatment for persistent atrial fibrillation in relation to heart failure.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Electric Countershock; Female; Flecainide; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Risk; Sotalol; Treatment Failure; Warfarin

Improved understanding of the reasons for underuse of diagnostic tests and treatments for congestive heart failure (CHF) may be helpful for designing future interventions to improve quality of care.. To determine differences between family physicians' and cardiologists' practice styles for diagnosis and treatment of CHF, a random sample of family physicians and cardiologists were surveyed with standardized case scenarios.. Survey respondents were 182 family physicians and 163 cardiologists. Family physicians were less likely than cardiologists to rate measurement of left ventricular ejection fraction as "very important" for patients with new CHF, less likely to order an echocardiogram or test for ischemia, and much less likely to identify diastolic dysfunction as a cause of CHF. Family physicians were more likely to prescribe digoxin when it was not indicated (diastolic dysfunction) and less likely to prescribe digoxin and an angiotensin-converting enzyme (ACE) inhibitor when they were indicated (moderately to severely reduced left ventricular ejection fraction). Family physicians expressed more concern over the risks of ACE inhibitors in patients with blood pressure of 100/70 mm Hg or serum creatinine of 2.0 mg/dL and were less likely to prescribe an ACE inhibitor in these settings. Family physicians overestimated the risks of warfarin use for atrial fibrillation and were therefore less likely to prescribe warfarin.. Family physicians appear to have less understanding of CHF pathophysiology (ie, systolic versus diastolic dysfunction) and how treatment differs according to the underlying disease process. Overestimation of the risk of ACE inhibitor and warfarin use may result in underprescribing these medications.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiology; Cardiotonic Agents; Digoxin; Drug Prescriptions; Echocardiography; Heart Failure; Humans; Male; Middle Aged; Physician-Patient Relations; Physicians, Family; Practice Patterns, Physicians'; Retrospective Studies; Stroke Volume; Surveys and Questionnaires; Warfarin

Topics: Anticoagulants; Biopsy, Needle; Cholangiography; Cholecystectomy, Laparoscopic; Endoscopy, Gastrointestinal; Fatal Outcome; Female; Follow-Up Studies; Heart Failure; Hemobilia; Humans; Middle Aged; Recurrence; Sarcoidosis; Warfarin

A 30-year-old female whose mitral valve had been replaced with a mechanical prosthetic valve 23 years ago gave birth to a healthy baby by cesarian section under controlled anticoagulant therapy. Warfarin was replaced with intravenous heparin just one week before cesarian section and heparin administration was stopped several hours prior to the operation which was successfully carried out without excessive blood loss. Although warfarin carries a risk of teratogenecity, fortunately, the baby had not any somatic malformation. We believe that pregnancy is not contraindicated in patients with mechanical prosthetic heart valves, however, a strict observation of the cardiac function during middle and late trimesters of gestation by echocardiography and planned anticoagulant therapy are necessary in order to prevent maternal congestive heart failure and thromboembolism and protect a neonate against intracranial hemorrhage.

Topics: Adult; Biomarkers; Blood Coagulation Factors; Cerebral Hemorrhage; Cesarean Section; Echocardiography; Female; Fibrinolytic Agents; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Mitral Valve Insufficiency; Monitoring, Physiologic; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Thromboembolism; Thrombolytic Therapy; Warfarin

A 50-year-old man experienced acute heart failure four years after initial mitral valve replacement (MVR) for left atrial thrombosis using a CarboMedics prosthesis, despite satisfactory coagulation control with warfarin. After initial MVR, late cardiac tamponade occurred twice and left circumflex branch stenosis was treated with percutaneous transluminal coronary angioplasty (PTCA). Re-MVR with an Edwards-TEKNA valve was performed after echocardiography and cineradiography showed mitral valve thrombosis, with thrombi on both mitral valve leaflets and covering most of the left atrial wall. Post-surgery progress was favorable with warfarin and dipyridamole therapy. After six weeks cardiac catheter revealed complete right external iliac artery occlusion. Cardiac dysfunction and atrial flutter apparently accelerated thrombosis after a common cold activated coagulation. Cardiac tamponade, circumflex branch stenosis, and right external iliac artery occlusion occurred despite satisfactory coagulation control by warfarin. Warfarin suppresses some coagulation factors but cannot always correct hypercoagulability. Two months after re-MVR, coagulation tests showed normal TT, F1 + 2, and D-Dimer but an increase in TAT, suggesting involvement of additional coagulation factors. After artificial valve replacement, therapy should achieve a PT-INR level of 3.0-4.5, with close follow-up using other indices of fibrinolysis and coagulation activity in addition to TT.

Topics: Acute Disease; Blood Coagulation; Blood Coagulation Factors; Fibrinolysis; Heart Failure; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Prosthesis Failure; Thrombosis; Warfarin

Congestive heart failure is a debilitating disease characterized by impaired cardiac function with accompanying activation of a variety of neural and hormonal counter-regulatory systems. Abnormal activity of the sympathetic nervous system and renin-angiotensin-aldosterone axis and a predisposition to the generation of fatal ventricular arrhythmias are often associated with the development of the disease. Although the underlying cause of sudden death in these patients remains to be unequivocally elucidated, abnormally increased cardiac sympathetic nervous activity may be involved.. Twenty-two patients with severe congestive heart failure (New York Heart Association functional class III or IV with left ventricular ejection fraction of 18 +/- 1%) and 29 healthy male volunteers participated in this study. By combining direct sampling of internal jugular venous blood via a percutaneously placed catheter with a norepinephrine and epinephrine isotope dilution method for examining neuronal transmitter release, we were able to quantify the release of central nervous system monoamine and indoleamine neurotransmitters and investigate their association with the increased efferent sympathetic outflow that is variably present in treated patients with this condition. Mean cardiac norepinephrine spillover was 145% higher in treated heart failure patients than in healthy subjects (P < .05), with norepinephrine release from the heart in 6 of 22 patients being more than the highest control value. Raised internal jugular venous spillover of epinephrine (26 +/- 12 versus 2 +/- 4 pmol/min, P < .05) and of norepinephrine and its metabolites (2740 +/- 480 versus 875 +/- 338 pmol/min, P < .05), indicative of increased central nervous system turnover of both catecholamines, occurred in cardiac failure and was quantitatively linked to the degree of activation of the cardiac sympathetic nervous outflow, as was the jugular overflow of the principal serotonin metabolite, 5-hydroxyindoleacetic acid.. An association between the degree of activation of central monoaminergic neurons and the level of sympathetic nervous tone in the heart was identified in treated patients with heart failure. Epinephrine neurons in the brain may contribute to the sympathoexcitation that is seen in this condition, with the activation of sympathoexcitatory noradrenergic neurons, most likely those of the forebrain, playing an accessory role.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiotonic Agents; Case-Control Studies; Central Nervous System; Digoxin; Dihydroxyphenylalanine; Diuretics; Epinephrine; Heart Failure; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Neurotransmitter Agents; Norepinephrine; Sympathetic Nervous System; Warfarin

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

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

A case is presented of a mechanical cardiac valve dysfunction occurring in a 19-year-old Nigerian 7 years after valve surgery and presenting with cardiac failure, supraventricular tachycardia and later, cardiogenic shock but initially masquerading as generalised bleeding probably from Warfarin-drug interaction. The problem of management of an artificial heart valve in our setting is discussed.

Topics: Adult; Antimalarials; Drug Combinations; Drug Interactions; Fatal Outcome; Heart Failure; Heart Valve Prosthesis; Humans; Male; Nigeria; Prosthesis Failure; Pyrimethamine; Shock, Hemorrhagic; Sulfadoxine; Tachycardia, Supraventricular; Warfarin

A 66-year-old man who had undergone MVR using a ST. Jude Medical valve entered the hospital with acute heart failure and cardiogenic shock 3 months after surgery. He had had a symptom of petechiae due to macrogloburinemia after initial MVR and had been in the poor control of anticoagulation therapy because of presence of petechiae. He was diagnosed as prosthetic valve thrombosis using echocardiography and underwent emergency re-MVR using a Central Open Bioprosthesis (COB) which was developed by our department. He was doing well 8 month after re-MVR. Selection of prosthetic valve should be performed carefully in the patient with hemorrhagic disease, and careful observation and proper anticoagulant therapy should be carried out after valve replacement.

Topics: Aged; Bioprosthesis; Heart Failure; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Prosthesis Failure; Reoperation; Thrombosis; Waldenstrom Macroglobulinemia; Warfarin

Topics: Aged; Atrial Fibrillation; Diazepam; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Hydrochlorothiazide; Kinetics; Male; Warfarin

We reviewed the experience with infective endocarditis at some major US Army Medical Centers. One hundred patients were studied, comparing 82 patients who had native valve endocarditis (NVE) with 18 patients who had prosthetic valve endocarditis (PVE). Among patients with PVE, four had porcine valves and 14 had synthetic. None of the patients with NVE had received anticoagulants; 14 of 18 patients with PVE had received anticoagulants. The major causes of death were central nervous system hemorrhage, congestive heart failure, uncontrolled infection, and embolic phenomena. The principal cause of death in patients with PVE was CNS hemorrhage. Of the patients with PVE, 36% had symptomatic cerebral hemorrhage while receiving anticoagulants and 80% of them died.

Topics: Anti-Bacterial Agents; Anticoagulants; Aortic Valve; Cerebral Hemorrhage; Drug Evaluation; Endocarditis, Bacterial; Heart Failure; Heart Valve Prosthesis; Humans; Mitral Valve; Postoperative Complications; Premedication; Prothrombin Time; Retrospective Studies; Thromboembolism; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Therapeutic; Endocarditis, Bacterial; Female; Heart Diseases; Heart Failure; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Two hundred twenty patients admitted to a Coronary Care Unit were studied by serial plasma fibrinogen chromatography--a method for quantification of HMWFCs, native fibrinogen, and other fibrinogen derivatives in plasma. Enhanced formation of fibrin (intravascular coagulation/thrombosis) is reflected by elevation of plasma HMWFC. One hundred ten patients suffering from documented acute myocardial infarction showed early, sharp elevation of plasma HMWFC (p less than 0.001 when compared to normal and cardiac control groups), a finding which persisted for 10 to 20 days after infarction. Forty-three of the patients did not receive anticoagulant therapy, and the others received either initial heparin, heparin plus warfarin, or werfarin therapy. Plasma fibrinogen chromatographic findings, days 1 to 5, did not differ between the anticoagulated and nonanticoagulated treatment groups, although there were minor differences in the data for days 6 to 10. The results demonstrate that patients with acute myocardial infarction develop a coagulopathy characterized by enhanced fibrin formation, which is influenced to only a minor degree by conventional dosage anticoagulant therapy.

Topics: Anticoagulants; Blood Coagulation Disorders; Fibrinogen; Heart Failure; Heparin; Humans; Myocardial Infarction; Warfarin

Replacement of the mitral valve with the Björk-Shiley tilting disc valve prosthesis was performed in 203 consecutive patients with isolated mitral valvular disease at Karolinska Sjukhuset, Stockholm, Sweden, during the 6-year period ending December 1975. Results with the Delrin and pyrolytic carbon disc prostheses were analysed with actuarial techniques and compared in terms of mortality rate, incidence of thrombo-embolism and frequency of re-operation. Early (4%) and late mortality rates (7.5 deaths per 100 patient years) were similar with both types of prostheses. No case of primary mechanical prosthetic failure was encountered. The pyrolytic carbon disc prostheses have obviously decreased the incidence of systemic emboli from 9.6 to 5.3 per 100 patient years and so far eliminated mortality due to embolization. This benefit is probably related to the increased opening angle from 50 degrees to 60 degrees in the pyrolytic carbon disc model, which causes less resistance to blood flow. Thrombotic obstruction of the prosthetic valve, however, has been a persistent problem in the order of 3.3 incidences per 100 patient years. Only one patient in twelve involved was referred to our clinic and could be saved by an emergency re-operation. The development of the ring-shaped radiopaque marker in the tilting disc occluder provides a valuable tool for instant diagnosis of partly or completely obstructed disc motion caused by thrombosis. Disc motion can be easily visualized by cineradiography or fluoroscopy. Early diagnosis of and emergency operation for thrombotic obstruction of the prosthesis will reduce the mortality due to this dangerous complication.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Child; Dicumarol; Evaluation Studies as Topic; Female; Follow-Up Studies; Heart Failure; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Myocardial Infarction; Thromboembolism; Time Factors; Warfarin

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Topics: Aged; Blood Coagulation Disorders; Female; Gastrointestinal Hemorrhage; Health Education; Heart Failure; Hematuria; Humans; Male; Maryland; Middle Aged; Outpatient Clinics, Hospital; Prothrombin Time; Thromboembolism; Time Factors; Warfarin

The clinical course, through pregnancy and delivery, of a 30-year-old woman with rheumatic heart disease and a prosthetic mitral valve is presented. Despite maternal development of congestive cardiac failure and atrial fibrillation, the delivery of a healthy infant was achieved. The problems encountered during pregnancy and delivery in patients with rheumatic heart disease and prosthetic valves are discussed. These include the management of long-term anticoagulant therapy, prophylaxis against rheumatic fever and subacute bacterial endocarditis, impaired cardiac function, atrial fibrillation, breast feeding, and contraception as they relate both to the mother and the fetus and infant.

Topics: Adult; Atrial Fibrillation; Breast Feeding; Digoxin; Endocarditis, Subacute Bacterial; Female; Fetus; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Penicillin G Benzathine; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Rheumatic Fever; Rheumatic Heart Disease; Sulfadiazine; Warfarin

Twenty-one patients with prosthetic cardiac valves successfully underwent transurethral prostatic resection at the Mayo Clinic. Temperature elevation in 4 patients was the only postoperative complication; in particular, neither congestive heart failure nor thromboembolic complications developed and there were no operative deaths. Preoperative evaluation and clinical management of potential complications are based on the recognition of the complications that are peculiar to these patients. Particularly important is the proper use of antibiotics and anticoagulants and avoidance of overloading the circulation with fluid from open prostatic venous sinuses.

Topics: Aged; Aortic Valve; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Preoperative Care; Prostatectomy; Sodium; Thromboembolism; Urethra; Vitamin K 1; Warfarin

Size-frequency distribution curves of erythrocytes were generated with the Coulter Counter in 73 normal subjects and patients. Mean corpuscular volume (MCV) determined by routine calculation and MCV determined by size-frequency distribution were similar in all normal subjects and in patients with a single population of erythrocytes. Some patients with iron-deficiency anemia, folate deficiency, and vitamin B12 deficiency had two discrete erythrocyte populations. Some patients with microcytic anemia were shown to have a population of normocytes in addition to the predominant microcytic population. Reticulocytes and normocytes were identified in two patients recovering from macrocytic anemia. Transfused blood was identified as a separate population in a patient with microcytic anemia. In cases with two erythrocyte populations, the MCV of the principal population, as determined from size-distribution curves, differed from the MCV of the entire erythrocyte pool, as was determined by routine methods. Analysis of sequential erythrocyte size distributions in patients under treatment demonstrated the dynamics of erythrocyte subpopulations. Anisocytosis was quantified and shown to be associated frequently with hospitalized patients.

Topics: Adenocarcinoma; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Brain Diseases; Electronics, Medical; Erythrocyte Count; Erythrocytes; Female; Folic Acid Deficiency; Heart Failure; Hematocrit; Hemorrhage; Humans; Male; Methotrexate; Middle Aged; Reticulocytes; Thrombophlebitis; Vitamin B 12 Deficiency; Warfarin

Eighty-four patients with mitral stenosis and cerebral embolism have been followed up for 20 years. Half of the series (those treated in the early years) had no anticoagulant treatment and half were given long-term warfarin therapy. Mortality rate and causes of death have been reviewed, and comparison of survival times of treated and untreated groups by life-table analysis bears out the immediate need for anticoagulants when a diagnosis of systemic embolism is established. It is wise to continue the treatment for six months but it may be reasonable to discontinue it after one year with patients who can be assured of regular review.

Topics: Adult; Aged; Atrial Fibrillation; Female; Follow-Up Studies; Heart Failure; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Mitral Valve Stenosis; Phenindione; Pneumonia; Recurrence; Warfarin

Topics: Acute Disease; Administration, Oral; Adult; Aged; Female; Half-Life; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Premedication; Time Factors; 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: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Cholesterol; Cholestyramine Resin; Clofibrate; Diet; Female; Heart Failure; Humans; Hyperlipidemias; Hyperthyroidism; Male; Middle Aged; Myocardium; Oxygen Consumption; Pacemaker, Artificial; Propranolol; Warfarin

Topics: Aged; Anticoagulants; Female; Heart Failure; Hemorrhage; Humans; Infarction; Necrosis; Skin; Skin Diseases; Warfarin

Topics: Adrenal Gland Diseases; Aged; Electrocardiography; Heart Failure; Hemorrhage; Heparin; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Organ Size; Pulmonary Edema; Thrombophlebitis; Warfarin

Topics: Anticoagulants; Arrhythmias, Cardiac; Coronary Disease; Geriatrics; Heart Diseases; Heart Failure; Humans; Thromboembolism; Warfarin

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Surgical Procedures; Digoxin; Endocarditis; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart, Artificial; Humans; Isoproterenol; Methicillin; Middle Aged; Postoperative Complications; Psychoses, Substance-Induced; Psychotic Disorders; Thoracic Surgery; Warfarin

Topics: Anticoagulants; Artificial Organs; Cardiac Catheterization; Cardiac Surgical Procedures; Heart Failure; Heart, Artificial; Heparin; Humans; Mitral Valve; Mitral Valve Stenosis; Pathology; Postoperative Complications; Prostheses and Implants; Radiography, Thoracic; Thoracic Surgery; Thrombosis; Warfarin

Topics: Abdomen; Abdomen, Acute; Diagnosis; Heart Failure; Heparin; Humans; Infarction; Intestine, Small; Intestines; Surgical Procedures, Operative; Warfarin

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

Topics: Angina Pectoris; Anticoagulants; Carotid Artery Thrombosis; Diabetic Angiopathies; Fibrinolysis; Gangrene; Heart Failure; Humans; Myocardial Infarction; Raynaud Disease; Thromboangiitis Obliterans; Thromboembolism; Warfarin