Clinical Implications of Recommendations in Current Guidelines on Anticoagulation in Patients with Atrial Fibrillation

Research Article

Austin J Clin Cardiolog. 2015; 2(2): 1038.

Clinical Implications of Recommendations in Current Guidelines on Anticoagulation in Patients with Atrial Fibrillation

Ozdemir E¹, Gursul E²*, Bayata S¹ and Safak O³

¹Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey

²Biga State Hospital, Canakkale, Turkey

³Burdur State Hospital, Burdur, Turkey

*Corresponding author: Erdal Gursul, Biga State Hospital , Kibris Sehitleri Street, Canakkale, Turkey

Received: March 30, 2015; Accepted: September 13, 2015; Published: October 01, 2015


Atrial Fibrillation (AF) is the most common arrhythmia in the clinics. We aimed to evaluate the clinical implications of anticoagulation in terms of warfarin that is recommended by current guidelines. Among patients having an indication for Oral Anti Coagulation (OAC), those under treatment with warfarin and those that are not taking were compared (n: 205). 117 of the 190 patients with an indication for OAC (57.0% of the patient population; 61.6% of those with an indication for OAC) were found to be taking OAC. 73 patients had an indication, but were not taking warfarin for a variety of reasons. 83 patients were detected, who had an indication for warfarin and did take warfarin, and found to have INR controls in the retrospective screening, 58 of which (69.9%) had an effective INR. No statistically significant differences were found between the groups who were taking and who were not taking warfarin, in terms of HAS-BLED and CHA2DS2-VASc scores (p = 0.656, p = 0.696, respectively). Treatment may not be initiated in patients with an indication for OAC treatment, due to patientrelated reasons, physician-related reasons, medication-related reasons, or therapeutic levels may not be achieved, or drug treatment is interrupted due to various reasons, as a result of patient non-compliance.

Keywords: Atrial fibrillation; Warfarin; INR


OAC - Oral Anticoagulant Therapy; AF - Atrial Fibrillation; INR - International Normalized Ratio; CAD - Coronary Arterial Disease; DM - Diabetes Mellitus; ECHO – Echocardiography; CRF - Chronic Renal Failure; CHF - Chronic Heart Failure


Atrial Fibrillation (AF) is a supraventricular tachyarrhythmia, which is the most common arrhythmia and its prevalence increases with ageing. Although AF is often associated with structural heart diseases, there is no structural heart disease in a considerable portion of patients with AF. Hemodynamic defects and thrombo-embolic events associated with AF cause significant morbidity and mortality [1]. Ischemic stroke is uppermost among thrombo-embolic events due to AF, and AF is a strong independent risk factor for ischemic stroke. Ischemic stroke risk in AF patients varies between 3% and 8% depending on other associated stroke risk factors [2]. Presence of associated structural heart diseases in AF further increases the stroke risk. Ischemic stroke which is a dramatic complication of AF is still an important issue because of its mortality, morbidity, adult disability and incurred costs as it was before.

Currently, in the light of previous studies the most effective treatment for preventing such an important and dramatic complication secondary to AF is Oral Anticoagulant Therapy (OAC) [3]. Randomized controlled studies have shown that OAC therapy achieving effective levels decreases ischemic stroke risk by 68% in unselected AF patients [4]. Also, even though new OAC drugs such as dabigatran, etexilate, rivaroxaban, apixaban are available, currently the most widespread treatment in our country and the world is still warfarin. In short, OAC therapy in AF is an accepted treatment method in preventing thrombo-embolic complications.

In this study, hospitalized patients having AF diagnosis according to criteria in European Society of Cardiology (ESC) 2010 AF treatment guideline and updated guideline published in 2012 were evaluated [5,6]. The patients’ use of warfarin and International Normalized Ratio (INR) effectiveness were evaluated and compared with demographic and clinical data. CHADS2 and CHA2DS2-VASc scores were simultaneously applied to patients and the patients with varying warfarin indication were determined [5,7]. The aim of our study is to evaluate clinical implications of guidelines on warfarin use in AF.

Material and Method


The medical records of patients hospitalized for any reason in our clinic which is a tertiary health institution between January 1, 2010 and March 31, 2012 were screened and 205 AF patients with adequate information were included into the study. Evaluated demographic and clinical data of the patients were as follows: age, sex, arterial hypertension, Diabetes Mellitus (DM), presence of vessel disease such as Coronary Arterial Disease (CAD) and peripheral arterial disease, smoking, thyrotoxicosis, presence of heart failure, diagnosis of rheumatic mitral valve, presence of cardiac valve prosthesis, previous ischemic stroke or transient ischemic attack or history of systemic embolism, presence of cardiomyopathy, hemogram, creatinine values, presence of chronic renal failure (CRF), dimension of left atrium, presence of spontaneous echo contrast or thrombus at left atrial appendix, number of hospitalizations, etiology of AF (valvular/ non-valvular AF). EF=40 was considered as Echocardiographically (ECHO) confirmed Cardiac Failure (CF). CHA2DS2-VASc and HASBLED scores were calculated in non-valvular AF [6,8].

AF classification

Valvular and non-valvular AF patients were determined. Patients with valve prosthesis, moderate-severe mitral stenosis or moderate-severe mitral insufficiency were considered as valvular AF patients. The patients without above mentioned valvular diseases were considered as non-valvular AF patients. The number of both groups of patients was determined and the groups were compared in terms of INR effectiveness. The patients were evaluated in 3 groups according to AF period. Paroxysmal AF episodes lasting less than 2 days with spontaneous resolution, persistant AF episodes lasting more than 7 days and requiring intervention with drugs or electrophysiological tools and permanent AF patients whose disease was accepted as being permanent [6]. The number of paroxysmal, persistent and permanent AF patients was determined and the groups were compared in terms of INR effectiveness.

Embolism and bleeding risk score systems in Nonvalvular AF

CHA2DS2-VASc, CHADS2 scores for anticoagulant indication and HAS-BLED to determine bleeding risk were calculated in non valvular AF. In 2001, CHADS2 scoring system was developed in order to determine embolism risk in non-valvular AF [7]. In calculating the score Chronic Heart Failure (CHF), age, Diabetes Mellitus (DM) are considered as 1 point and stroke as 2 points. The highest score is 6 and in patients with a score of =2 to start anticoagulant therapy is recommended. CHADS2 scores are calculated and mean of the score and number of patients with and without anticoagulant indication were determined. By CHADS2 scoring system low risk patients were thought to be overlooked; thus, in 2012 CHA2DS2- VASc score was developed [6]. In CHA2DS2-VASc scoring system CHF, hypertension, DM, vessel disease, age between 64-75 years and female sex are considered as 1 point and age over 75 years, ischemic cerebrovascular disease and systemic emboli as 2 points. The highest score is 9point and in patients with a score of 2 to start anticoagulant therapy is recommended. The CHA2DS2-VASc score of the patients was calculated and the number of patients with and without anticoagulant indication according to CHA2DS2-VASc scoring system was determined. The patients were separated into 3 groups according to CHA2DS2-VASc score: patients with a score of 0, 1 and 2. The number of the patients in each group was determined and INR effectiveness was compared between groups. The patients requiring different recommendations for anticoagulant therapy based on CHADS2 and CHA2DS2-VASc scores were determined and characteristics of the patients were reported. To determine bleeding risk in non valvular AF HAS-BLED scoring system was developed. [7] In HAS-BLED scoring system hypertension (systolic blood pressure over 160 mmHg), abnormal kidney (chronic dialysis or presence of renal transplant or serum creating in =200 mmol/L)/abnormal liver function (chronic liver disease or aspartat aminotransferase/ alanin aminotransferase/ alkalin phospatase >3x ULN together with bilirubin >2 x ULN), stroke, history of or tendency for bleeding, labile INR (time within therapeutic range is <60% or non-stable, high INR values, advanced age (>65 years), concomittant drug use (such as antiplatelet agents, nonsteroidal anti-inflammatory drugs)/alcohol intake are considered as 1 point. Patients with a score of = 3 were considered as having high risk for bleeding. HAS-BLED risk score of the patients was calculated and the number of patients in the low/ high risk groups was determined.

Anticoagulant therapy

Presence of valvular AF (valve prosthesis with AF and echocardiographically confirmed moderate-severe mitral stenosis or moderate-severe mitral insufficiency with AF) is considered as indication for warfarin use. In presence of non-valvular AF CHA2DS2- VASc score was evaluated. Presence of one of the other parameters along with CHA2DS2-VASc score = 2 and female sex is considered as indication for anticoagulant therapy in non-valvular AF. The indications for antiplatelet therapy (aspirin/aspirin+clopidogrel) and/or anticoagulant therapy were evaluated. Patients taking indicated anticoagulant therapy, patients taking anticoagulant therapy without indication and patients not taking anticoagulant therapy while there’s no indication for it were determined. The reason for not taking anticoagulant therapy in patients having an indication for this therapy was looked for. By screening medical records number of patients not taking anticoagulant therapy because of undetermined reason, patient’s rejection of the therapy, history of major bleeding and high HAS BLED score was determined as the reasons for not taking the drug. INR effectiveness was evaluated in control patients taking warfarin with indication for this therapy. The patients having INR measurement at least once a month were considered as patients checked for INR effectiveness and patients with no INR measurement after baseline and/or patients having INR measurement with an interval of more than a month were considered as patients not checked for INR effectiveness. If in more than 60% of the follow up period INR was 2.0 - 2.5 in non-valvular AF and 2.5-3.0 in valvular AF, then INR was considered as effective; otherwise ineffective. The number of patients not checked for INR effectiveness was determined.

Statistical Analysis

Quantitative data were shown as mean ± std. (Standart Deviation) in tables. Categorical data were shown as n (number) and percentage (%). In analysis of quantitative data conformity with normal distribution Kolmogorov-Smirnov test was used, and in variables with normal distribution parametric methods and in variables with abnormal distribution nonparametric methods were used. In comparisons between groups Pearson Chi-Square and Fisher’s exact test statistical analysis were used. p<0, 05 was considered as statistically significant and p=0, 05 as statistically insignificant. In assessing the findings of the study, statistical analysis of data was done by using SPSS (Statistical Package for Social Sciences) 15.0 for Windows software package by 95% confidence.


109 of the 205 patients (53.2%) included into the study were female and mean age was 68, 57±13, 68 years. Distribution of 190 patients with anticoagulant indication according to CHA2DS2- VASc score was as follows: paroxysmal AF in 33 patients (17, 4%), persistent AF in 50 patients (26, 3%), permanent AF in 107 patients (56, 3%). 162 (79%) patients had non-valvular AF and 32 (15, 6%) of the valvular AF patients had mitral valve disease and 11 (5.4%) had valve prosthesis. In 7 of patients (4.4%) with non-valvular AF there was no risk factor for embolism (CHA2DS2-VASc=0). There was 119 patients (58.1%) taking warfarin and 86 patients (41.9%) not taking warfarin. HAS-BLED scores of non-valvular AF were as follows: 81 patients (50.0%) had a score of < 3 and 81 patients (50.0%) = 3 (Table 1).