Warfarin Therapy For Atrial Fibrillation Research Articles

Meta-analysis study on direct oral anticoagulants vs warfarin therapy in atrial fibrillation and PCI: Dual or triple approach?

BackgroundDual antiplatelet therapy and anticoagulants may be required in the case of coexistence of coronary artery disease and atrial fibrillation (AF) undergoing (PCI), with associated increased bleeding rates. The introduction of direct oral anticoagulants (DOACs), however, significantly reduced the incidence of bleeding complications in this clinical setting of patients. We therefore sought to assess whether the recent publication of the AUGUSTUS and ENTRUST-AF PCI studies significantly impacted current evidence on the use of DOACs in AF patients treated with PCI.MethodsWe performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed pooled estimates of risk ratios (RRs) and 95%CIs for any bleeding (AB), cardiovascular events (CVE), and death at follow-up: 12,542 patients have been included in the analysis. We particularly analyzed data comparing dual anti-thrombotic therapy (DOAC plus single anti-platelet therapy) with triple (DOAC plus dual anti-platelet therapy).ResultsWhen compared with patients receiving standard triple therapy with warfarin, patients receiving DOACs had a significantly lower risk of AB (RR 0.65; 95% CI, 0.61–0.70, p < 0.00001) and of MB (RR 0.63; 95% CI, 0.53–0.73, p < 0.00001). The risk of cardiovascular events and mortality were comparable between DOAC and VKA groups (RR 1.05, 95% CI 0.93–1.18, RR 1.14, 95% CI 0.94–1.37, respectively, p n.s.). Similar results were observed comparing triple therapy vs dual therapy.ConclusionsDOACs are safer than and as effective as warfarin when used in patients with AF undergoing PCI; dual therapy with DOACs is comparable to triple therapy in terms of safety and efficacy.

Warfarin therapy in atrial fibrillation: assessment of patient knowledge of risks and benefits

ABSTRACT Patients with atrial fibrillation are at an increased risk for stroke, and many benefits from anticoagulation. Despite the emergence of direct oral anticoagulants, many patients continue to rely on warfarin for their anticoagulation due to logistical, pharmacokinetic, clinical, or patient preference issues. Previous work has suggested that outcomes of warfarin therapy are related to patient education/knowledge. We assessed knowledge of indications, benefits, and complications of warfarin therapy in 99 randomly selected patients enrolled in the Warfarin Anticoagulation Clinic at the Mayo Clinic in Florida who were taking warfarin for non-valvular atrial fibrillation. Patients were labeled as ‘knowledgeable’ or ‘not knowledgeable’ regarding warfarin therapy according to the results of a cross-sectional questionnaire. The majority of patients in both the knowledgeable and not knowledgeable groups displayed understanding that they were taking warfarin for atrial fibrillation (valvular vs non-valvular atrial fibrillation was not an included answer choice). However, there was a clear lack of knowledge amongst patients with atrial fibrillation in both groups about their stroke risk while on and off warfarin, and their risk of major bleeding or adverse events related to their warfarin therapy. There was only a significant difference between the two groups regarding their knowledge of what increases or decreases the risk of bleeding while on warfarin. There was no major difference between the groups with regards to demographic and medical characteristics, except that ‘not knowledgeable’ patients tended to have more peripheral vascular disease, ulcer disease, and moderate-severe renal disease compared to ‘knowledgeable’ patients.

Importance of HAS-Bled Score in Patients on Warfarin Therapy for Atrial Fibrillation

Importance of HAS-Bled Score in Patients on Warfarin Therapy for Atrial Fibrillation

Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based Cohort of Atrial Fibrillation

ObjectiveTo study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF). Patients and MethodsWe conducted an observational population-based study of 2800 nondemented patients with incident AF from January 1, 2000, through December 31, 2010. The association of incident dementia with warfarin therapy and TTR was examined using Cox proportional hazards regression models. ResultsMean patient age was 71.2 years; 53% were men (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a mean ± SD follow-up of 5.0±3.7 years. After adjusting for confounders, warfarin therapy was associated with a reduced incidence of dementia (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest quartiles of TTR were associated with lower risk of dementia. A 10% increase in TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI, 0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were associated with decreased risk of dementia. ConclusionIn the community, warfarin therapy for AF is associated with a 20% reduction in risk of dementia. Increasing TTR on warfarin is associated with reduced risk of dementia. The risk of dementia was reduced with a reduction in time spent in subtherapeutic and supratherapeutic international normalized ratio range. Effective anticoagulation may prevent cognitive impairment in patients with AF.

Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy for Atrial Fibrillation as a Test Case.

ObjectivesTo construct and validate a prediction model for individual combined benefit and harm outcomes (stroke with no major bleeding, major bleeding with no stroke, neither event, or both) in patients with atrial fibrillation (AF) with and without warfarin therapy.MethodsUsing the Kaiser Permanente Colorado databases, we included patients newly diagnosed with AF between January 1, 2005 and December 31, 2012 for model construction and validation. The primary outcome was a prediction model of composite of stroke or major bleeding using polytomous logistic regression (PLR) modelling. The secondary outcome was a prediction model of all-cause mortality using the Cox regression modelling.ResultsWe included 9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In the derivation cohort (n = 4632), there were 136 strokes (2.94%), 280 major bleedings (6.04%) and 1194 deaths (25.78%) occurred. In the prediction models, warfarin use was not significantly associated with risk of stroke, but increased the risk of major bleeding and decreased the risk of death. Both the PLR and Cox models were robust, internally and externally validated, and with acceptable model performances.ConclusionsIn this study, we introduce a new methodology for predicting individual combined benefit and harm outcomes associated with warfarin therapy for patients with AF. Should this approach be validated in other patient populations, it has potential advantages over existing risk stratification approaches as a patient-physician aid for shared decision-making

Late leakage from four-branch prosthetic graft after total aortic arch repair.

We present two cases with late graft leakage of unknown aetiology after open total aortic arch repair (TAR). Case 1: a 73-year-old woman underwent TAR for arch aneurysm with 24-mm four-branch graft. She had a previous history of pacemaker implantation for sick sinus syndrome and warfarin therapy for atrial fibrillation. Follow-up computed tomography (CT) revealed increased low-density area around the graft 4 years after surgery and blood leakage was shown in delayed-phase CT. Thoracic endovascular aortic repair (TEVAR) was performed to cover the haematic leakage, and shrinkage of the lesion was achieved 1 month after TEVAR. Case 2: a 72-year-old man with diabetes mellitus, hypertension and hyperlipidaemia was admitted to our institute for treatment of aortic arch aneurysm. TAR was successfully performed; however, leakage from the prosthetic graft was noticed by expert radiologists in follow-up delayed-phase CT scan 6 years after surgery. The leakage was resolved 1 month after TEVAR. Although the cause of late leakage was not determined, the slowly expanding haematoma proved to be treatable by additional TEVAR.

Stroke associated with discontinuation of warfarin therapy for atrial fibrillation

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

Socioeconomic status and risk of hemorrhage during warfarin therapy for atrial fibrillation: A population-based study

Among patients taking warfarin, lower socioeconomic status is associated with poorer control of anticoagulation. However, the extent to which socioeconomic status influences the risk of hemorrhage is unknown. We examined the extent to which socioeconomic status influences the risk of hemorrhage in older individuals newly commencing warfarin therapy for atrial fibrillation. We conducted a population-based cohort study of individuals 66 years or older with atrial fibrillation who commenced warfarin therapy between April 1, 1997, and November 30th 2011, in Ontario, Canada. We used neighborhood-level income quintiles as a measure of socioeconomic status. The primary outcome was an emergency department visit or hospitalization for hemorrhage, and the secondary outcome was fatal hemorrhage. We studied 166,742 older patients with atrial fibrillation who commenced warfarin therapy. Of these, 16,371 (9.8%) were hospitalized for hemorrhage during a median follow-up of 369 (interquartile range 102-865) days. After multivariable adjustment using Cox proportional hazards regression, we found that those in the lowest-income quintile faced an increased risk of hospitalization for hemorrhage relative to those in the highest quintile (adjusted hazard ratio 1.18, 95% CI 1.12-1.23). Similarly, the risk of fatal hemorrhage (n = 1,802) was increased in the lowest-income relative to the highest-income quintile (adjusted hazard ratio 1.28, 95% CI 1.11-1.48). Among older individuals receiving warfarin therapy for atrial fibrillation, lower socioeconomic status is a risk factor for hemorrhage and hemorrhage-related mortality. This factor should be carefully considered when initiating and monitoring warfarin therapy.

Warfarin therapy for atrial fibrillation in haemodialysis patients: mind the (evidence) gap

Warfarin therapy for atrial fibrillation in haemodialysis patients: mind the (evidence) gap

A case of factitious hyponatremia and hypokalemia due to the presence of fibrin gel in serum

We describe here the case of a 84-year-old woman under warfarin therapy for atrial fibrillation, who was admitted to the Emergency Department for severe gluteal hemorrhage. Blood samples were drawn after patient admission and transported within 20 min to the laboratory. Results of laboratory testing revealed a markedly increased value of international normalized ratio and extremely low values of serum sodium (60 mmol/L) and potassium (1.4 mmol/L). A second serum sample was collected approximately 2 h after the former, showing normal values of both sodium (145 mmol/L) and potassium (3.5 mmol/L). The analysis of the specimen collected upon patient admission revealed the presence of a small, transparent fibrin gel in the serum, which was partially aspirated by the sample probe of the instrument. This case underscores the importance that serum samples need to be allowed to clot completely prior to centrifugation and analysis, especially those collected from patients under anticoagulant treatment.

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Spontaneous intramural small-bowel hematoma due to a rare complication of warfarin therapy: Report of two cases

Spontaneous intramural small-bowel hematoma secondary to warfarin therapy has been reported in the literature, but this complication of anticoagulant therapy is still considered rare. Here we report two cases of spontaneous nontraumatic jejunal intramural hematoma treated in our institution. After emergent admission for acute abdomen, both cases were found to have a history of warfarin therapy for atrial fibrillation. Prothrombin time, activated partial thromboplastin time, and international normalized ratio were elevated in both cases. For Case 1, abdominal computed tomography revealed segmental mural thickening with precontrast hyperdensity and perienteric haziness affecting the distal jejunum. The patient underwent emergent laparotomy under the impression of mesentery occlusion with impending bowel ischemia due to her history of atrial fibrillation. Abdominal computed tomography for Case 2 revealed jejunal intramural hematoma and bloody ascites. The patient received conservative therapy with nil by mouth, fresh frozen plasma transfusion, and vitamin K1 supplementation, and no surgical intervention was done based on experience gained with the first case. Although a few other recent cases have been reported, the differences in our two cases were especially helpful in demonstrating that surgery can be avoided. We suggest that a history of anticoagulant use with prolonged international normalized ratio values in patients presenting with abdominal pain should alert physicians to consider spontaneous intramural small-bowel hematoma secondary to warfarin therapy. Recognizing this syndrome is important in order to avoid unnecessary surgery because excellent outcomes can be achieved with conservative treatment.

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin. We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism). We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged. In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.

Role for the left atrial appendage occlusion device in managing thromboembolic risk in atrial fibrillation

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

Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack

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

Initiation and Persistence with Warfarin Therapy in Atrial Fibrillation According to Ethnicity

The aim of this study was to investigate initiation of and persistence with warfarin treatment in patients with atrial fibrillation (AF) according to ethnicity. Patients hospitalized with first-time AF from 1997 to 2009, prescription claims of warfarin and country of birth were identified by individual-level linkage of nationwide administrative agencies. Cox proportional hazards models were used to estimate the relationship between covariates affecting initiation and non-persistence with warfarin treatment. A total of 151,537 patients were included in the study and 5,061(3.3%) were of non-Danish origin. CHADS2 score distribution varied substantially according to ethnicity, the proportion of patients with CHADS2 score ≥1 being 79.2, 78.1, 65.9, and 46.0% for patients of Danish, Western, Eastern, and African origin, respectively. 79,239(52.4%) of all patients initiated treatment with warfarin at some point in time. Multivariable Cox proportional hazard analyses indicated patients of Eastern and African origin were less likely to initiate warfarin therapy (HR 0.75; 95% CI 0.69–0.82 and HR 0.58; 95% CI 0.44–0.76, respectively). Patients of Eastern origin were more likely to interrupt treatment (HR 1.23; 95% CI 1.02–1.47; for all patients; HR 1.62; 95% CI 1.22–2.16; for patients with CHADS2 score >1). African origin was associated with a trend to interrupt treatment (HR 1.44; 95% CI 0.46–4.47; for patients with CHADS2 score >1). Initiation of and persistence with warfarin in AF patients is lower among patients of Eastern and African origin compared to patients of Danish and Western origin, despite equal access to health care and medication. Future studies should address, beyond ethnicity, all possible driving factors of (non)initiation and persistence with treatment in general. This will be particularly interesting in light of the new generation of anticoagulants, which might render different adherence to treatment.

Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

AbstractSingle-nucleotide polymorphisms in genes that affect warfarin metabolism (cytochrome P450 2C9 gene, CYP2C9) and response (vitamin K epoxide reductase complex 1 gene, VKORC1) have an important influence on warfarin therapy, particularly during initiation; however, there is a lack of consensus regarding the optimal pharmacogenetics-based initiation strategy. We conducted a prospective cohort study in which patients requiring warfarin therapy for atrial fibrillation or venous thromboembolism were initiated with a novel pharmacogenetics-initiation protocol (WRAPID, Warfarin Regimen using A Pharmacogenetics-guided Initiation Dosing) that incorporated loading and maintenance doses based on genetics, clinical variables, and response (n = 167, followed up for 90 days), to assess the influence of genetic variations on anticoagulation responses. Application of the WRAPID algorithm resulted in a negligible influence of genetic variation in VKORC1 or CYP2C9 on time to achievement of first therapeutic response (P = .52, P = .28) and risk of overanticoagulation (P = .64, P = .96). After adjustment for covariates, time to stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype. Importantly, time spent within or above the therapeutic range did not differ among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time course of the anticoagulation response among the genotype groups was similar and predictable. We demonstrate the clinical utility of genetics-guided warfarin initiation with the WRAPID protocol to provide safe and optimal anticoagulation therapy for patients with atrial fibrillation or venous thromboembolism.

Antikoagulan Tedaviye Bağlı Kas İçi Kanamalar: İleri Yaş Bir Risk Faktörü müdür?

Oral anticoagulant therapy (OAT) is very effective in the prevention of cerebral embolism, especially in certain cardiac diseases. Hematomas are the major complication of OAT. It may threaten the patient’s life by bleeding into the vital structures. Herein, we describe four patients with hematomas in the psoas, quadriceps, pectoral, or rectus abdominis muscles accompanied by anemia during warfarin therapy for atrial fibrillation and artificial heart valves. Computed tomography and magnetic resonance imaging helped us establish a definitive diagnosis in each case. Our patients were three women and one man. Their international normalized ratios were within the therapeutic range during this period. They suffered from minor traumas, such as falls or a hit while taking warfarin therapy. All anticoagulation treatments were discontinued for approximately 1 week after the episode of bleeding. Although conservative management was sufficient for three patients, one patient had surgical decompression due to a rectus abdominis hematoma with retroperitoneal hemorrhage. There were no episodes of bleeding or other complications after starting oral anticoagulant therapy during the follow-up. The common aspects of our cases were older age and a history of minor trauma. As a result, we suggest that special attention needs to be paid to the patients under anticoagulant therapy, especially those at an advanced age, and to warn them avoid trauma. (Archives of Neuropsychiatry 2010; 47: 267-70)

172 Effectiveness of warfarin therapy for atrial fibrillation in a real world population

BACKGROUND: In patients with atrial fibrillation (AF), randomized controlled trials (RCT) indicate that dose-adjusted warfarin is effective in ischemic stroke prevention. However, there is disparity between RCT results and real-world practice in regards to poor INR control, number of monitoring visits and long term compliance. Therefore, we aim to evaluate the clinical characteristics, percentage of adequate anticoagulation and clinical outcomes of patients with AF in a real world population. METHODS AND RESULTS: We performed a retrospective analysis on a randomly selected group of patients (n 147) who visited the anticoagulation clinic (ACC) between March and June 2008. A long term clinical follow-up was available for all patients until June 2010 or the end of anticoagulant therapy. The mean age was 72 10 years and 39% were females. Comorbidities were hypertension 81%, diabetes 31% and previous stroke 14%. The average CHADS2 score was 2.1 1.2. During the follow-up time (median: 813; range: 50-820 days), the mean adequate anticoagulation was 68% 17% and the mean INR was 2.5 0.2. The mean number of visits was 9 5 per year. At clinical follow-up the rate of all cause mortality, myocardial infarction (MI) and stroke was 1.4% for each event. In addition, the rate of bleeding was 5.4% (2.7% for major or life threatening bleeding). In a subgroup analysis of patients younger than 75 years (group 1, n 76 and mean age 65 / 7 years) and older than 75 years (group2, n 71 and mean age 80 / 4 years), no significant difference was noted regarding, hypertension 82% vs. 85%, previous stroke 11% vs.15%, average INR 2.4 0.2 vs. 2.5 0.2 and adequate anticoagulation 68 18% vs. 67 17% respectively; all P NS. However, the group 1 had more diabetes 39% vs. 21%; P 0.010 and the group 2 had more females 32% vs. 48%; P 0.020. During the follow-up period, no difference was found between the group 1 and 2 regarding all cause mortality (1.3% vs. 1.4 %), MI (0% vs. 2.8%) and stroke (1.3%vs. 1.4%) respectively; all P NS. Finally, the group 2 had a higher rate of bleeding (11.3% vs. 0%; P .001) with 5.6% for major or life threatening bleeding. CONCLUSION: In a real world population, achieving therapeutic INR was suboptimal in a cost of frequent visit and mobilisation of numerous resources. Despite intensive monitoring, bleedings are frequent mainly in the elderly population. This study emphasizes the need of new oral anticoagulants that do not require monitoring and achieve a more predictable efficacy with less bleeding events. 173 SILENT ATRIAL FIBRILLATION IN OLMSTED COUNTY: A COMMUNITY-BASED STUDY

Dabigatran Challenges Warfarin’s Superiority for Stroke Prevention in Atrial Fibrillation

Marc Fisher MD Kennedy Lees MD Section Editors: Atrial fibrillation (AF) remains a prominent cause of ischemic stroke worldwide. The incidence of AF increases with age and prevalence reaches 10% in octogenarians.1 The proportion of strokes attributable to this common arrhythmia will continue to rise as our population ages. In the Framingham Study, almost one fourth of all strokes that occurred in patients aged >80 years were attributable to AF.2 Furthermore, cerebral infarctions in patients with AF tend to be larger than strokes caused by most other etiologies and result in high rates of both disability and mortality.3 In use for >50 years, the anticoagulant warfarin was first shown to prevent stroke in patients with AF 2 decades ago. A series of randomized trials demonstrated an exceptional level of efficacy (relative risk reductions close to 70%) for prevention of ischemic stroke and surprisingly low rates of intracerebral hemorrhage or major systemic bleeding.4 Despite this remarkable performance in clinical trials and strong endorsement by international guidelines, both physicians and patients have been reluctant to embrace warfarin therapy in AF. Underuse is typically attributed to the inconvenience of coagulation monitoring, complexities associated with drug and dietary interactions as well as the perception that hemorrhage rates may have been underestimated in the clinical trials. It is estimated that only approximately half of warfarin-eligible patients with AF actually receive anticoagulation.5 Furthermore, even those who are treated are often not maintained in the therapeutic range. This is due in part to warfarin’s nonlinear pharmacokinetics, but also its interaction with multiple other hepatically metabolized drugs and dietary intake of vitamin K that competes with warfarin’s synthetic inhibition of vitamin K-dependent clotting …