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The prevalence of atrial fibrillation (AF) is related to age and is projected to rise exponentially as the population ages and the prevalence of cardiovascular risk factors increases. The risk of ischemic stroke is significantly increased in AF patients, and there is evidence of a graded increased risk of stroke associated with advancing age. Oral anticoagulation (OAC) is far more effective than antiplatelet agents at reducing stroke risk in patients with AF. Therefore, increasing numbers of elderly patients are candidates for, and could benefit from, the use of anticoagulants. However, elderly people with AF are less likely to receive OAC therapy. This is mainly due to concerns about a higher risk of OAC-associated hemorrhage in the elderly population. Until recently, older patients were under-represented in randomized controlled trials of OAC versus placebo or antiplatelet therapy, and therefore the evidence base for the value of OAC in the elderly population was not known. However, analyses of the available trial data indicate that the expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. An important caveat with warfarin treatment is maintenance of a therapeutic international normalized ratio, regardless of the age of the patient, where time in therapeutic range should be ≥65%. Therefore, age alone should not prevent prescription of OAC in elderly patients, given an appropriate stroke and bleeding risk stratification. [ABSTRACT FROM AUTHOR]

Background: Multiple factors influence warfarin metabolism and can significantly affect the risk of adverse events. The extent to which patients understand the modifiable factors that impact on warfarin safety and efficacy is unclear. Methods: A 52-item questionnaire related to knowledge of warfarin was administered to patients with atrial fibrillation in a face-to-face interview with a dietitian. Results were compiled based on five categories: general warfarin knowledge, compliance, drug interactions, herbal or vitamin interactions, and diet. Results: 100 patients were surveyed. Stroke risk factors included hypertension (57%), heart failure (36%), age >75 years (33%), diabetes (22%), and prior stroke/transient ischemic attack (29%). The majority were either high-school (49%) or college graduates (27%). Ten (10%) had a stroke while on warfarin, 11 (11%) had a blood transfusion, and 26 (26%) had at least one fall. The percentages correct for questionnaire items in the five categories were as follows: general knowledge (62%), compliance (71%), drug interactions (17%), herbal or vitamin interactions (7%), and diet (23%). Neither education level nor duration of therapy correlated with warfarin knowledge. Patients at highest risk of stroke had very low knowledge scores in general. Discussion: Patients on warfarin have a poor general understanding of the medication, particularly those at highest risk of stroke. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Clinical guidelines for the management of atrial fibrillation and atrial flutter provide recommendations for anticoagulation based on patients'' overall risk of stroke. To determine the real-world compliance of physicians with these recommendations, we conducted a retrospective cohort study examining the utilization of warfarin in atrial fibrillation/flutter patients by stroke risk level. Methods: Patients with a qualifying atrial fibrillation/flutter diagnosis during ≥18 months'' continuous enrollment between January 2003 and September 2007, and with ≥6 months'' eligibility after the first atrial fibrillation/flutter diagnosis, were identified from the US MarketScan database (Thomson Reuters, New York, NY). Warfarin use within 30 days of the first diagnosis was assessed according to stroke risk, estimated using the Congestive heart failure, Hypertension, Age >75 years, Diabetes, Stroke (CHADS2) score. Results: Of 171,393 patients included in the analysis, 20.0% had a CHADS2 score of 0 (low risk), 61.6% a score of 1-2 (moderate risk), and 18.4% a score of 3-6 (high risk). Warfarin, recommended for high stroke-risk patients, was given to only 42.1% of those with a CHADS2 score of 3-6. A similar percentage of patients with moderate (43.5%) or low stroke risk (40.1%) received warfarin. Only 29.6% of high-risk, 33.3% of moderate-risk, and 34.1% of low-risk patients who were started on warfarin received uninterrupted therapy for 6 months following their initial prescription. Conclusions: These data suggest that guideline recommendations that anticoagulation should be provided in accordance with stroke risk in atrial fibrillation patients are not routinely followed in clinical practice. The causes and clinical implications of under-utilization of anticoagulation in atrial fibrillation patients with high stroke risk warrant further study. [Copyright &y& Elsevier]

Thromboembolism is a severe complication in atrial fibrillation. This overview presents thromboembolic disease as a single entity, ranging from stroke through mesenteric ischemia to acute limb ischemia. The PubMed, Embase, and Cochrane databases were systematically searched for the terms “atrial fibrillation” and “thromboembolism” in reports published from January 1986 to September 2009. The information of 10 evidence-based practice guideline documents and 61 further sources was systematically extracted. In atrial fibrillation, the average annual stroke risk is increased by 2.3% (lethality 30%). The annual incidence of acute mesenteric ischemia is 0.14% (lethality 70%), and that of acute limb ischemia is 0.4% (lethality 16%). In total, approximately 80% of embolism-related deaths are from stroke and 20% from other systemic thromboembolism. The ischemic symptoms generally have an acute onset but may mimic other diseases, particularly in mesenteric ischemia. Early diagnosis and treatment can limit or even prevent tissue infarction. Guideline-recommended therapy with aspirin or warfarin reduces the thromboembolic risk. Suitable patients may optimize their warfarin therapy by self-monitoring of the international normalized ratio (INR). New oral and parenteral anticoagulants with more stable pharmacokinetics are being developed. In conclusion, atrial fibrillation predisposes to thromboembolism. If ischemic stroke or systemic thromboembolism occurs, early diagnosis and treatment can improve outcomes. The thromboembolic risks are reduced by guideline-adherent antithrombotic therapy with warfarin or aspirin. Future directions may include self-monitoring of the international normalized ratio and novel anticoagulants. [Copyright &y& Elsevier]

Background: Genetic variants of the warfarin sensitivity gene CYP2C9 have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.Objective: Would testing patients with non-valvular atrial fibrillation (AF) for CYP2C9 before initiating warfarin improve outcomes?Design: Markov state transition decision model.Setting: Ambulatory or inpatient settings necessitating new initiation of anticoagulation.Patients: The base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culprit CYP2C9 alleles.Measures: Quality-adjusted life years (QALYs).Results: In the base case, testing and treating patients with CYP2C9*2 and/or CYP2C9*3 with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.Conclusion: For patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: We aimed to determine the level of INR control associated with reduced stroke and mortality. Material and methods: The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK. Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (>5 INR tests) categorised as at moderate or high risk of stroke (CHADS2 score ≥2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS2 score. Outcome measures were time to stroke and mortality. Results: 6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS2 score ≥2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range. Conclusions: Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR. [Copyright &y& Elsevier]

Abstract: Objectives: This study examined compliance with prescribing guidelines for antithrombotic therapy in patients with atrial fibrillation (AF) in Taiwan, using the 2001 joint guideline from the American College of Cardiology, American Heart Association, and European Society of Cardiology. The study also sought to identify factors associated with the appropriate prescribing of antithrombotic therapy. Methods: Patients with AF were identified by the presence of ≥2 inpatient or outpatient claims with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 427.31 in the Taiwanese National Health Insurance claims database between July 1, 2003, and June 30, 2004. Patients were stratified according to their stroke risk (highest, high, low, or lowest) and antithrombotic medication (aspirin, warfarin, ticlopidine/clopidogrel, or none). Based on these categories, rates of prescribed treatments that were compliant with the antithrombotic guidelines were calculated. Antithrombotic therapies were considered guideline compliant when warfarin was prescribed for the highest- or high-risk patients, aspirin was prescribed for low-risk patients, and aspirin or no antithrombotic treatment was prescribed for the lowest-risk patients. Because the role of ticlopidine/clopidogrel in AF remains unclear, prescription of these drugs without aspirin or warfarin was considered noncompliant with the guidelines. Results: Of 39,541 identified patients with AF, 70.3% were at high risk for thromboembolic events and 18.3% were at highest risk; however, only 24.7% of the overall population received appropriate antithrombotic therapy. When patients with risk factors for bleeding were excluded, the rate of compliance increased to 26.2%. Factors that were inversely associated with prescription of warfarin included risk factors for bleeding (cancer, predisposition to falls, previous hemorrhage, history of peptic ulcer, cirrhosis, renal dialysis, and psychiatric disease), hypertension, coronary artery disease, thyrotoxicosis, and age ≥60 years. Conclusions: Most of these patients with AF in Taiwan did not receive appropriate antithrombotic therapy over the period studied. Bleeding risk factors, hypertension, coronary artery disease, thyrotoxicosis, and older age were associated with low rates of warfarin use. [Copyright &y& Elsevier]

This article reports on a clinical trial that sought to compare the use of idraparinux to vitamin K antagonists to prevent thromboembolism in patients with atrial fibrillation. Non-valvular atrial fibrillation is the leading cause of stroke and studies have showed that anticoagulation with vitamin K antagonists can reduce the risk of stroke by a third. Despite that, the use of the drugs in clinical practice is limited due to the risk of bleeding and the complexity of monitoring the dosage. Researchers are hoping to find an unmonitored, fixed-dose anticoagulant that will be effective. This study was not the answer. It had to be stopped after patients getting the idrapariux bled excessively.

Warfarin is underused for stroke prevention in atrial fibrillation (AF). Previous studies addressing this have lacked longitudinal assessment. This study sought to characterize contemporary warfarin use in new-onset AF and evaluate its change over time. It was hypothesized that AF recurrence has an important influence on warfarin use patterns. One thousand five adults from 17 centers in the United States and Canada were enrolled into a prospective observational registry after their first documented episodes of AF. Detailed demographic, clinical history, and management data were collected on all subjects at enrollment, including medication use. Patients were followed at regular intervals for interim events and changes in AF management. Warfarin use at baseline and last follow-up (mean 25 ± 8 months) after enrollment was modeled using multivariate analysis. Initially, 65% of subjects were prescribed warfarin, but only 44% were taking it at 30 months. Even in “ideal” candidates for warfarin, the rate of warfarin prescription decreased from 70% at baseline to 50% at 30 months. Stroke risk factors, including hypertension, congestive heart failure, valvular heart disease, and previous stroke or transient ischemic attack were significant predictors of warfarin prescription at baseline. At last follow-up, the relation between AF recurrence and warfarin use (odds ratio 2.3, 95% confidence interval 1.6 to 3.1) was stronger than that for any individual stroke risk factor. In conclusion, predictors of warfarin use in patients with AF include AF recurrence and selected stroke risk factors. The discontinuation of warfarin in a large number of patients with AF over time is a cause for concern in light of data from recent clinical trials. [Copyright &y& Elsevier]

Presents a case of a 60-year-old woman with two year history of paroxysmal atrial fibrillation which progressed into persistent AF. Definition and epidemiology of AF; Risk factors; Classification of AF; Clinical course of the disease; Risks and benefits of anticoagulation; Optimal intensity of anticoagulation; Best candidate for the therapy; The factors that influence the decision to take warfarin; Status of clinical research on AF; Recommendations for this patient; Questions and discussion with a cardiologist.

The author explores his views on left atrial appendage occlusion. He highlights the risk of stroke posed to three million Americans who have atrial fibrillation. He discusses the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) as the clinical trial for evaluating the Watchmen percutaneous device which is a self-expanding structure made of nitinol. He downplays the precision of the primary efficacy estimate in PROTECT-AF trial. He also describes providing long-term warfarin therapy to patients with atrial fibrillation as challenging.

This article comments on a study in this issue which looked at the risk of stroke in older patients on warfarin or aspirin for atrial fibrillation. The study found warfarin was superior to aspirin in the prevention of stroke and was no more harmful to the patients in terms of major haemorrhage. The author maintains that the subjects of the study had a lower prevalence of risk factors for stroke overall and that the challenge will be to see if the results are the same on higher risk patients.

The article focuses on sex as a risk factor of ischemic stroke in atrial fibrillation. According to the author, women were discovered to have a much higher rate of thromboembolism when not taking warfarin. With warfarin, the incidence of thromboembolism was almost the same in both sexes and complications were comparable. It was shown that anticoagulation therapy with warfarin can reduce the risk of thromboembolic events in patients with atrial fibrillation.