Adherence to Guidelines on Anticoagulant Management Among Adult Patients with Atrial Fibrillation at the Philippine General Hospital

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1 Philippine Journal of Internal Medicine Original Article Adherence to Guidelines on Anticoagulant Management Among Adult Patients with Atrial Fibrillation at the Philippine General Hospital Leora Flor Macapugay, M.D.*; Giselle G. Gervacio, M.D.*; Felix Eduardo R. Punzalan, M.D.*; Jodette Joy H. Lavente, M.D.* Abstract Background: Atrial fibrillation (AF) is the most common cause of embolic stroke. Although there is impressive risk reduction in stroke associated with warfarin therapy in clinical trials and guidelines on anticoagulation in AF, there are limited data on how well these goals are being met. This study aims to determine the adherence to guidelines on anticoagulant management among adult patients with AF at the Department of Internal Medicine Ward of the University of the Philippines - Philippine General Hospital (UP-PGH). Methods: This is a prospective study, which included patients aged 8 years and older with diagnosis of AF, which can be paroxysmal, persistent, longstanding or permanent. Upon admission, patients were interviewed and information like age, gender, duration of AF, co-morbid illnesses, and medical history were collected using a checklist. Risk factors for bleeding, use of antiplatelet/anticoagulant agents and International Normalized Ratio (INR) values were also determined. Results: There were 40 subjects included in the study, majority of which were female (77.5%) and in the years age range (35%). There were 2 (52.5%) patients who had valvular AF and 9 (47.5%) who had non-valvular AF. Of those patients with valvular AF, 80.9% received warfarin. Of those patients with non-valvular AF, 94.7% were at moderate or high risk for thromboembolism, but only 47.4% of those patients received warfarin. We found that only a small percentage of patients (6%) had INR in the therapeutic range of The majority of the patients had their INR in the sub-therapeutic ranges at 40% and 24% at INR values of and respectively. The majority of the patients on warfarin had INR monitoring 30 days, and these were patients already on chronic or long-term warfarin use. Those patients who had more frequent INR monitoring were those newly initiated on the treatment whose INR values where in the sub-therapeutic range. Conclusion: The adherence of anticoagulant management among AF patients admitted at the Internal Medicine Wards of UP-PGH, to evidencebased clinical practice guidelines, was high at 80.9% for patients with valvular AF and was quite low at 47.4% for non-valvular AF patients. Patients were found to have low bleeding risks based on a HAS-BLED score and patients with moderate to high thromboembolic risk factors were more often prescribed with warfarin, although only a few patients achieved a therapeutic INR. A more frequent INR monitoring including a close follow-up with the patients should be performed to achieve target INR in most patients with AF. Moreover, we should not discount starting anticoagulation in patients with non-valvular AF who have moderate to high thromboembolic risk factors. Keywords: atrial fibrillation, anticoagulation, warfarin, anticoagulation guidelines Introduction Atrial fibrillation (AF) is the most common cause of embolic stroke, which is an event that produces a high rate of neurologic disability and death. Evidence-based clinical practice guidelines recommend the use of warfarin therapy (International Normalized Ratio [INR], ) for AF patients who are at highest *Philippine General Hospital - University of the Philippines Manila Reprint request to: Jodette Joy H. Lavente, M.D., Philippine General Hospital - University of the Philippines Manila, Taft Avenue, Ermita, Metro Manila 000, jjhl82@yahoo.com risk for stroke, i.e., valvular heart disease, patients with a previous stroke or transient ischemic attack, hypertension, structural heart disease, or left ventricular dysfunction, or in patients aged 75 years or older. -3 For patients with AF who are 65 to 75 years and who have one of these risk factors for stroke, warfarin is recommended. For patients in this age group without risk factors for stroke, warfarin or aspirin therapy should be used, depending on a patient s risk of bleeding. -3 For AF patients in whom warfarin therapy is declined, contraindicated, or not tolerated, use of the newer anticoagulant (dabigatran), 4 or aspirin, or aspirin and clopidogrel is recommended. In a study by Bradley, et al. 5 on the frequency Volume 52 Number 3 July-September, 204

2 Macapugay LF, et al. Adherence to Guidelines on Anticoagulant Management of anticoagulation for AF and reasons for its nonuse at the Veterans Affairs Medical Center, the rate of warfarin use was 5%, with an estimated rate of 67% in all indicated cases and 89% in cases without contraindications. Of 2,327 international normalized ratio (INR) tests performed in this period, 87% were therapeutic, 9.0% were low (<.5),and 4.0% were high (>4.0). Of the 494 patients who did not receive warfarin, 240 (43%) had documentation of being prescribed aspirin. Thus, the number of patients with AF receiving warfarin or aspirin in this study was 708 (7%). Stafford and Singer found that warfarin use in AF patients without contraindications in a sample of US practices increased from approximately 3% in 989 to 40% by 993, coincident with the publication of the large randomized trials. 6 Antani and colleagues found that only 37% of 98 patients received warfarin when indicated in Albers and colleagues found that only 36% of 309 patients with AF admitted to US university hospitals from 992 to 994 were receiving warfarin, and that at discharge, only 44% of patients with risk factors for stroke without contraindications received warfarin. 8 However, a larger study found that patients with AF at tertiary care hospitals were twice as likely to be discharged on anticoagulation as patients at community hospitals, but neither setting achieved a particularly high rate (42% vs 2%). 9 Based on the yearly census in our institution, the estimated number of patients admitted with AF is approximately 200 in a year but to date no prevalence studies have been conducted. There is also no data on how many of these AF patients with indications for anticoagulation receive said therapy. Although there is impressive risk reduction in stroke associated with warfarin therapy in clinical trials and the existence of guidelines on anticoagulation in AF, there are limited data on how well these goals are being met. Internationally, numerous randomized controlled trials of warfarin have conclusively demonstrated that long-term anticoagulation therapy can reduce the risk for stroke by approximately 68% per year in patients with non-valvular AF, and even more in patients with valvular AF. 0 This study will be relevant in finding out whether there is concordance between the randomized controlled trial evidence and clinical practice patterns in PGH. The primary objective of the study was to determine the physician s adherence to the guidelines on anticoagulant management among adult patients with AF at the Department of Internal Medicine Ward of PGH. Moreover, this study aimed to describe cardiovascular profile, risk for stroke and bleeding risk and complications among patients with AF receiving anticoagulation and to determine the quality of PT monitoring for warfarin in terms of achieving target INR levels and frequency of monitoring of INR. Materials and Methods Inclusions and Exclusions The study included patients aged 8 years and older with diagnosis of AF. For the purposes of this study, patients were included if a diagnosis of AF is confirmed within 24 hours of admission by means of an electrocardiogram or chart documentation of a diagnosis of AF. Atrial fibrillation is defined as a supraventricular arrhythmia characterized electrocardiographically by low amplitude baseline oscillations (fibrillatory or f waves) and an irregular ventricular rhythm. AF that terminates spontaneously within seven days is termed paroxysmal; AF that is present continuously for more than seven days is called persistent, AF persistent; for more than one year is termed longstanding, and longstanding; AF that is refractory to cardioversion is termed permanent. In this study, patients were included if they had paroxysmal, persistent, long-standing or permanent AF, but patients with secondary AF due to a temporary condition (i.e. electrolyte abnormality, infection) or medical procedure who reverted to sinus rhythm on further follow-up were excluded. Study Setting, Population and Study Period The study ran for three months, from January to March 202, and included all patients admitted at Ward One and Ward Three of the PGH Internal Medicine Ward. Within 24 hours of admission, all the patients at Ward One and Ward Three were screened. The patients who met the inclusion criteria were interviewed using a checklist and their medical charts were reviewed within 24 hours of inclusion. Data Collection and Analysis Information such as age, gender, duration of AF, comorbid illnesses, and medical history were collected from the patients satisfying the study entry criteria. Risk factors for bleeding based were also recorded through a checklist. Use of warfarin or aspirin, aspirin + clopidogrel, and other antiplatelet/anticoagulant agents and all INR values (and the dates on which they were obtained) during the three-month study period were also determined. The distribution of patients with AF receiving any type of anticoagulation was determined. The cardiovascular profile of AF patients including their risk for cardioembolic events (using the CHA 2 -VASC Score for non-valvular AF) were described as well as the type of anticoagulant used. The CHA2DS2 -VASC Score is a validated scoring system to guide antithrombotic therapy in patients with non-valvular AF 2 Volume 52 Number 3 July-September, 204

3 Adherence to Guidelines on Anticoagulant Management Macapugay LF, et al. based on various stroke risk factors 2,3 and has been used in the new European Society of Cardiology (ESC) guidelines for the management of AF. The risk factors for stroke and the corresponding points for each can be seen in Table I. majority of which were female (77.5%) and in the years age range (35%). Almost all (97.5%) had permanent AF with valvular heart disease (52.5%) and hypertension (45%) as the most common co-morbid conditions. (Table III). C H Condition Table I: CHA2DS2 -VASC Score Congestive heart failure (or Left ventricular systolic dysfunction) Hypertension (blood pressure above 40/90mmHg or treated hypertension on medication) A2 Age 75 years 2 D Diabetes Mellitus S2 Prior Stroke or Transient Ischemic Attack (TIA) 2 V Vascular disease (eg. Peripheral arterial disease [PAD], Coronary Artery Disease [CAD], myocardial infarction, aortic plaque) A Age years Sc Sex category (i.e. female gender) Points Stroke risk assessment should also be accompanied by assessment of risk of bleeding. Thus, the distribution of AF patients with risk of bleeding and the type of anticoagulant used was also determined. Bleeding risk assessment was done using a validated bleeding risk scoring system such as the HAS-BLED Scores. 4 The bleeding risk factors based on the HAS-BLED scores can be seen in Table II. Condition Table II: HAS BLED score H Hypertension (Systolic blood pressure 60mmHg) A Abnormal renal function (defined as the presence of chronic dialysis or renal transplantation or serum creatinine 200µmol/L (>~2.3 mg/dl)) AND / ORAbnormal liver function (defined as chronic hepatic disease (eg. cirrhosis) or biochemical evidence of significant hepatic derangement (eg. bilirubin >2x upper limit of normal, in association with AST/ALT/ALP >3x upper limit normal) S Stroke (Previous history of stroke) B L Bleeding (Major bleeding history (anemia or predisposition to bleeding)) Labile INR*s (refers to unstable/high INRs or poor time in therapeutic range (eg<60%)) E Elderly (age 65) D Drug Therapy (concomitant therapy such as antiplatelet agents, NSAID's); AND / OR Alcohol intake (consuming eight or more alcoholic drinks per week) *INR= International Normalized Ratio Points Lastly, for patients started on warfarin therapy, the frequency of INR monitoring was determined as well as the last determined INR prior to hospital discharge. Results Table III: Baseline characteristics of patients with atrial fibrillation Characteristic Age (7.5%) (2.5%) (35%) (0%) (25%) 75 4 (0%) Gender Male 9 (22.5%) Female 3 (77.5%) Type of Atrial fibrillation Unable to determine 0 Paroxysmal (2.5%) Permanent 39 (97.5%) Risk factors for stroke Hypertension 8 (45%) Coronary Artery Disease 3 (7.5%) Congestive Heart Failure 5 (37.5%) Stroke/ Transient Ischemic Attack (27.5%) Diabetes 3 (7.5%) Arterial Thrombosis 0 Valvular heart disease 2 (52.5%) Presence of mechanical valves 3 (7.5%) Echocardiographic findings LVH 3 (77.5%) Spontaneous Echo Contrast/Rheologic stasis Intracardiac Thrombus 2 (5%) Risk factors for bleeding Bleeding history 7 (7.5%) Frequent falls 0 Dementia 0 Blood Dyscrasia 0 Vascular malformation 0 Inability to cooperate with therapy 2 (5%) Seizure disorder 0 Liver disease 0 Other potential contraindications to warfarin therapy Warfarin allergy 0 Patient refusal of warfarin 2 (5%) Active cancer/terminal illness 0 No. (%) of patients (Total n=40) 0 There were 40 subjects included in the study, Volume 52 Number 3 July-September, 204 3

4 Macapugay LF, et al. Adherence to Guidelines on Anticoagulant Management There were 2 (52.5%) patients who had valvular AF and 9 (47.5%) who had non-valvular AF. Seventeen of the 2 (80.9%) patients with valvular AF received warfarin as anticoagulant. There were four (9%) patients with valvular AF who did not receive warfarin due to patients refusal (two patients) and inability to comply with INR monitoring (two patients) and was on aspirin (9.5%) and aspirin and clopidogrel (9.5%) instead. Of the 9 patients who had non-valvular AF, 6 (84.2%) had CHA2DS2 VASc Score of 2. Almost half of them (42.%) received warfarin with the remainder receiving aspirin (5.8%), aspirin + clopidogrel (0.5%) and warfarin + aspirin (5.3%). Two patients (0.5%) did not receive any anti-coagulant despite having a CHA2DS2 VASc Score of 2. One of these patients was admitted for hemorrhagic stroke and the other had a recent history of upper gastrointestinal bleeding due to peptic ulcer disease (Table IV). When it comes to the bleeding risks of these patients, Table V showed that most of the subjects have low HAS-BLED Scores, with 42.5% having a score of 0 and 40% having a score of. Majority of them were on warfarin as anticoagulant at 64.7% and 56.2% with HAS-BLED Score of 0 and respectively. For patients given warfarin (n=25), the frequency of INR monitoring was determined and Table VI showed that for 40% of patients INR monitoring was done every 30 days or more, and most of these patients were on long term warfarin use. More frequent INR monitoring was done in those newly initiated on warfarin treatment. Table VII showed that of the 25 patients on warfarin, 9 (76%) were on chronic warfarin use with 4 (56%) on continuous chronic warfarin use, with five (20%) on chronic warfarin but currently on hold. Table IV: Distribution of study patients and the type of anticoagulant and/or antiplatelet used Indication for anti-coagulation TREATMENT No.(%) of patients Warfarin Aspirin None (n=40) Aspirin & Warfarin Aspirin + Clopidogrel Other Anticoagulants Valvular AF 7 (80.9%) 2(9.5%) 0 2(9.5%) 0 0 2(52.5%) Non-valvular AF 0* * 2* 8 (42.%) 2(0.5%) 3 (5.8%) (5.3%) 2(0.5%) 0 (5.3%) 2(0.5%) 9(47.5%) *CHA2DS2 -VASC Score: C=Congestive heart failure (or Left ventricular systolic dysfunction), pt; H=Hypertension, pt; A2=Age 75 years, 2pts; D=Diabetes Mellitus, pt; S2=Prior Stroke or TIA, 2pts; V= Vascular disease (eg. PAD, CAD, myocardial infarction, aortic plaque), pt; A= Age years, pt; Sc=Sex category (i.e. femalegender), pt. Table V: Risk factors for bleeding and type of anticoagulant and/or antiplatelet used HAS-BLED Score* Treatment No. of patients Warfarin Aspirin Aspirin & Warfarin Aspirin + Clopidogrel Other anticoagulants None (n=40)% 0 (64.7%) 3(7.6%) 0 2(.8%) 0 (5.9%) 7 (42.5%) 9(56.2%) 3(8.7%) (6.3%) 2(2.5%) 0 (6.3%) 6 (40%) 2 4(66.7%) (6.6%) (6.6%) 6 (5%) 3 (00%) (2.5%) *H- hypertension (SBP=60), (Points: ); A-Abnormal renal function (defined as the presence of chronic dialysis or renal transplantation or serum creatinine 200µmol/L (>~2.3 mg/dl)), (Points: ); Abnormal liver function (defined as chronic hepatic disease (eg. cirrhosis) or biochemical evidence of significant hepatic derangement (eg. bilirubin >2x upper limit of normal, in association with AST/ALT/ALP >3x upper limit normal) (Points: ); S- Stroke (Previous history of stroke) (Points: ); Bleeding (Major bleeding history (anemia or predisposition to bleeding)) (Points: ); L- Labile INRs (refers to unstable/high INRs or poor time in therapeutic range(eg<60%))(points: ); E- Elderly (age >/= 65) (Points: ); D- Drug Therapy (concomitant therapy such as antiplatelet agents, NSAID s) (Points: ); A- Alcohol intake (consuming 8 or more alcoholic drinks per week) (Points: ) Table VI: Frequency of monitoring of INR* Interval between INR determinations No. of patients, n=25 (%) 3 days 4 (6%) 5 days (4%) 7 days 4 (6%) 4 days 2 (8%) 5-30 days 4 (6%) 30 days 0 (40%) *For patients given warfarin (including those with warfarin on hold) Warfarin was on hold for reasons such as patients being admitted for procedures necessitating temporary cessation of warfarin (four patients), or due to significant bleeding (periorbital hematoma) in one patient. Six (24%) were newly started on warfarin treatment. Overall, only 6% had INR in the therapeutic range of The majority of patients had their INR in the sub-therapeutic ranges at 40% and 24% at INR values of and respectively. 4 Volume 52 Number 3 July-September, 204

5 Adherence to Guidelines on Anticoagulant Management Macapugay LF, et al. Table VII: Distribution of last INR values prior to discharge Patient category INR Values Total No. of patients Newly started on warfarin 2/6 (8%) 3/6 (2%) /6 (4%) 0/6 0/6 0/6 6(24%) Chronic Warfarin use 2/4 (8%) 5/4 (20%) 3/4 (2%) 3/4 (2%) /4 (4%) 0/4 4(56%) Warfarin on hold 2/5 (8%) 2/5 (8%) 0/5 0/5 0/5 /5 (4%) 5(20%) Total No. of patients, n=25 (%) 6(24%) 0(40%) 4(6%) 3(2%) (4%) (4%) Discussion Patients with AF have a stroke risk that is increased four- to five-fold than persons without AF. 5 Atrial fibrillation accounts for up to 5% of strokes in persons of all ages and 30% in patients over the age of 80 years. 6 A 999 meta-analysis found that warfarin, a vitamin K antagonist, reduced the relative risk of ischemic stroke by 62% compared with placebo. 7 Aspirin was found to offer modest protection against stroke (relative risk reduction, 22%; 95% CI, 2-38). Although warfarin was significantly more efficacious in preventing stroke than aspirin (relative risk reduction, 36%; 95% CI, 4-52), it also increased the risk of major hemorrhage. 7 The benefit of stroke prevention with the use of warfarin is offset by an increased risk of bleeding in patients with low risk of thromboembolism. Thus, the American College of Chest Physicians (ACCP) and the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) recommend that antithrombotic therapy be prescribed according to an individual s thromboembolic risk. 8,2,3 For patients with non-valvular AF, they recommend using the CHA2DS2 VASc scoring system to determine the type of anti-thrombotic therapy to give. The maximum CHA 2 VASc score is 9.0 and A CHA 2 -VASc score =0 corresponds to a truly low risk, 2 and thus the recommendation is to prescribe either aspirin or no antithrombotic therapy, but no antithrombotic therapy is preferred. 3 Based on the ESC guidelines on AF, oral anticoagulation is recommended or preferred for patients with one or more stroke risk factors (i.e. a CHA 2 -VASc score of.0 and above). For patients with valvular AF, antithrombotic therapy with warfarin is recommended with a target INR of In this study population, of those patients with valvular AF and thus had a clear indication for anticoagulation therapy with warfarin, 80.9% received the said treatment. For those patients with nonvalvular AF, 94.7% were at moderate or high risk for thromboembolism (CHA2DS2-VASc score of.0 and above). The 20 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation 4 recommend the use of anticoagulants warfarin or dabigatran in such patients, although in this study, only 47.4% of those patients received warfarin. Patients who had hypertension or CAD were more likely to be given anti-platelet therapy (either aspirin or aspirin + clopidogrel) rather than warfarin, as what was seen in our study. In other countries, rates of reported anti-thrombotic prescription compliance have ranged from 24% 3 in a Swedish study 2 to 59% (based on the 2004 ACCP recommendations) in patients newly diagnosed with AF in a large Seattle-based health plan. 20 The rate of warfarin prescribing in Western countries since 999 has been reported to range from 37% to 67%. 20,2 A study in Taiwan 22 showed that the rate of prescribing appropriate anti-thrombotic therapy was 38.9% based on the 2006 AHA/ACC/ESC recommendations. In our study, though the population is quite small, we were able to show that the rate of anti-thrombotic prescription compliance at 47.4%, although low, was similar to previously reported rates in other countries. As mentioned before, the benefit of stroke prevention with the use of warfarin is offset by an increased risk of bleeding, especially in patients with low risk of thromboembolism. Thus, stroke risk assessment should always include an assessment of bleeding risk. This study used a validated bleeding risk stratification score for those on anticoagulants in AF: the HAS-BLED Score (see methods). A score of 3.0 or more indicates increased one year bleed risk on anticoagulation sufficient to justify caution or more regular review. The risk is for intracranial bleed, bleed requiring hospitalization or a hemoglobin drop > 2g/L or that needs transfusion. 4 In our study, the majority had low HAS-BLED score, and only 2.5% had a score of 3, but despite this low risk of bleeding in the population, there were two (0.5%) patients who were not given any anti-thrombotic therapy even with an indication to do so (CHA2DS2-VASc score 2). One of these patients was admitted for hemorrhagic stroke and another had a recent history of upper gastrointestinal bleeding due to peptic ulcer disease, both having high HAS-BLED scores. The efficacy and risks of oral anti-coagulation are largely associated with maintaining the quality of anticoagulation control. Warfarin can significantly reduce stroke risk but can be difficult to dose and monitor because of its recommended narrow therapeutic range of In this study, we found that only a small percentage of patients (6%) had Volume 52 Number 3 July-September, 204 5

6 Macapugay LF, et al. Adherence to Guidelines on Anticoagulant Management INR in the therapeutic range of The majority of the patients had their INR in the sub-therapeutic ranges at 40% and 24% at INR values of and 0-.49, respectively. The majority of the patients on warfarin had INR monitoring 30 days, and these were patients already on chronic or long-term warfarin use. Those patients who had more frequent INR monitoring were those newly initiated on the treatment, with an average hospital stay of 4.8 days. These patients newly initiated on warfarin also had their INR values in the sub-therapeutic range. Monitoring and adjustment of warfarin dose were planned for on an out-patient basis. The lower international normalized ratio seen in our study was also observed in several Asian studies, reporting that an INR of warfarin (.5-2) than normally used is well tolerated and effective in Chinese patients However, this observation differed from the findings of Western studies. 26 The conflicting results may point to differences in thromboembolic and bleeding risks between races, although this has not been validated. Limitations of the Study The study had several limitations. First of these limitations was the small population size. Another limitation was that, the proportion of time spent in the therapeutic INR, strongly associated with reduced risk of both bleeding and thromboembolism, was not determined in this analysis. This was mainly because the study population was that of in-patients and no follow-up INR determinations were done on an out-patient basis. Another limitation was factors that might have caused subtherapeutic INR like diet or compliance to medications were not included in the analysis. We recommend that further studies on anticoagulant management in patients with AF would take these factors into consideration. Conclusion The adherence to anti-coagulant management among AF patients admitted at the Internal Medicine Wards of the UP-PGH to evidence-based clinical practice guidelines was high at 80.9% for patients with valvular AF and was quite low at 47.4% for non-valvular AF patients. Patients were found to have low bleeding risks and patients with moderate to high thromboembolic risk factors were more often prescribed with warfarin, although only a few patients achieved a therapeutic INR. A more frequent INR monitoring including a close follow-up with the patients should be performed to achieve target INR in most of the patients with AF. Moreover we should not discount starting anticoagulation in patients with non-valvular AF who have moderate to high thromboembolic risk factors. References. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 200;3(9): Fuster V, Ryden LE, Cannom DS, et al. for the American College ofcardiology/american Heart Association Task Force on Practice Guidelines; the European Society of Cardiology Committee for Practice Guidelines; the European Heart Rhythm Association; and the Heart Rhythm Society. 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7 Adherence to Guidelines on Anticoagulant Management Macapugay LF, et al. (ATRIA) Study. Ann Intern Med. 999.;3:9 0. Furie KL, Kasner SE, Adams RJ et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American stroke association. Stroke ;: Bonow R, Mann D, Zipes D, Libby P. Braunwald s Heart Disease. A textbook of Cardiovascular Medicine. Ninth Ed Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J, Selmer C, Ahlehoff O, Olsen AM, Gislason GH, Torp-Pedersen C. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 20;342:d Lip G, Nieuwlaat R, Pisters R, Lane D, Crijns H. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach: The Euro Heart Survey on Atrial Fibrillation. Chest ;2: Lip G, Frison L, Halperin J, Lane, D. Comparative Validation of a Novel RiskScore for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation.The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score.JACC. 20; 57: Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent riskfactor for stroke: the Framingham Study. Stroke. 99;22: Idem. Atrial fibrillation: a major contributor to stroke in the elderly: theframingham Study. Arch Intern Med 987;47: Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy toprevent stroke in patients with atrial fibrillation: A meta-analysis. Ann Intern Med. 999;3: Guyatt G, Akl E, Crowther M, Gutterman D, Schuüremann H. Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. 202;4(2_ suppl):7s-47s. 9. Friberg L, Harnmar N, Ringh M, et al. Stroke prophylaxis in atrial fibrillation: Who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study). EurHeartJ. 2006;27: Glazer NL, Dublin S, Smith NL, et al. Newly detected atrialfibrillation and compliance withantithrombotic guidelines. ArchIntern Med. 2007;67: Nieuwlaat R, Capucci A, Camm AJ, et al. for the European HeartSurvey Investigators. Atrial fibrillation management: A prospective survey in ESC member countries: The Euro Heart Survey on Atrial Fibrillation. Eur Heart J. 2005;26: Li-Jen L, Ming-Hui C, Cheng-Han L, Der-Chang W, Ching-Lan C, and Yea-Huei KY. Compliance with Antithrombotic Prescribing Guidelines for Patients with Atrial Fibrillation A Nationwide Descriptive Study in Taiwan. Clinical Therapeutics ;9: Cheung CM, Tsoi TH, Huang CY. The lowest effective intensity ofprophylactic anticoagulation for patients with atrial fibrillation. Cerebrovasc Dis. 2005;20: Yasaka M, Minematsu K, Yamaguchi T. Optimal intensity of internationalnormalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation. Intern Med. 200;40: You JH, Chan FW, Wong ES, Cheng G. Is INR between 2.0 and 3.0 theoptimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation? BrJClinPharrnacol. 2005;59: Odin A, Fabian M, Hart RG. Optimal INR for prevention of stroke and death in atrial fibrillation: A critical appraisal. Thrornb Res. 2006;7: Volume 52 Number 3 July-September, 204 7