Iraqi J Pharm Sci, Vol.28(1) 2019 CHADS2 and CHA2DS2-VASc scores in Iraqi AF patients DOI: https://doi.org/10.31351/vol28iss1pp101-105 101 Status of CHADS2 and CHA2DS2-VASc Scores in Predicting Risk of Stroke and its Prevention in Iraqi Patients with Atrial Fibrillation Mohanad Y. Al-Radeef *,1 *Department of Clinical Pharmacy, College of Pharmacy, University of Tikrit, Tikrit, Iraq. Abstract Atrial fibrillation is associates with elevated risk of stroke. The simplest stroke risk assessment schemes are CHADS2 and CHA2DS2-VASc score. Aspirin and oral anticoagulants are recommended for stroke prevention in such patients. The aim of this study was to assess status of CHADS2 and CHA2DS2-VASc scores in Iraqi atrial fibrillation patients and to report current status of stroke prevention in these patients with either warfarin or aspirin in relation to these scores. This prospective cross-sectional study was carried out at Tikrit, Samarra, Sharqat, Baquba, and AL- Numaan hospitals from July 2017 to October 2017. CHADS2 and CHA2DS2-VASc scores were manually calculated. One hundred patients were participated, 48 were men and 52 were women. Their mean age was 62.56 ± 14.36 years. Permanent type of atrial fibrillation, palpitation, and hypertension were the most diagnosed type, symptom and comorbidity recorded in this study respectively. Average scores of CHADS2 and CHA2DS2-VASc were 2.34 ± 1.39 and 4.1 ± 2.05, respectively. These scores were not calculated for these patients in hospital setting. Aspirin and warfarin were prescribed regardless to these scores. The result of this study indicated that CHADS2 and CHA2DS2-VASc scores were often neglected in hospitals; and aspirin is still widely used as a strategy to minimize the risk of stroke. Keywords: Atrial fibrillation, CHADS2, CHA2DS2-VASc, aspirin, warfarin. في منها الدماغية والوقاية السكتة خطر توقع في VASc-2DS2CHA و 2CHADS درجات حالة األذيني بالرجفان المصابين العراقيين المرضى 1*،مهند ياسر الرديف الصيدلة السريرية ، كلية الصيدلة ، جامعة تكريت ، تكريت ، العراق .فرع * الخالصة و 2CHADSأبسط مخططات تقييم خطر السكتة الدماغية هي درجة يرتبط الرجفان األذيني بزيادة خطر اإلصابة بالسكتة الدماغية. VASc-2DS2CHA .ةالفموي التخثر مضاداتللوقاية من السكتة الدماغية في مرضى الرجفان االذيني عادة ما ينصح باستعمال األسبرين و. األذيني بالرجفان المصابين العراقيين المرضى في VASc -2DS2CHAو 2CHADS درجات حالة تقييم كان الهدف من هذه الدراسة هو .الدرجات هذه الى نسبة الوارفارين أو األسبرين باستخدام المرضى هؤالء لدىالدماغية السكتة من الوقاية مستوى وتحديد االول تشرين إلى 2017 تموز من والنعمان وبعقوبة وشرقاط وسامراء تكريت مستشفيات فيالمقطعية المستعرضة الدراسة هذه أجريت .يدويا VASc -2DS2CHAو 2CHADS درجات احتساب تم 2017. كان .سنة5662  3614 كان همأعمار متوسط .امرأة 52 و رجل 48 منهم ،ى الرجفان االذينيمرضمن مئةشارك في هذه الدراسة الدراسة هذه فياالكثر توثيقا المشترك لواالعتال األعراض تشخيًصا، األكثر النوعهم الدم ضغط وارتفاع خفقانال األذيني، الرجفان من الدائم النوع العمل يتم لم .التوالي على  34 ,2 1, 39و VASc -2DS2CHA 05 ,2  1 ,4 و 2CHADS الدرجات متوسط .التوالي على .الدرجات هذه عن النظر بغض والوارفارين األسبرين وصف تمو المذكورة المستشفيات في المرضى لهؤالء الدرجات بهذه نطاق على يستخدم األسبرين يزال الو المستشفيات؛ في تهمل ما غالبا VASc -2DS2CHAو 2CHADS درجاتاظهرت الدراسة ان الدماغية. بالسكتة اإلصابة رخط لتقليل كاستراتيجية واسع , االسبرين, الوارفارين.VASc-2DS2, CHA2CHADSالكلمات االفتتاحية : الرجفان االذيني, Introduction Atrial fibrillation (AF) is a type of supraventricular arrhythmia that is characterized by uncoordinated activation in trial electricity with irregular and often fast ventricular response triggering hemodynamic compromise (1). Roughly, 1 in 100 of general population is thought to develop AF, while in elderly cohorts, the prevalence usually exceeds 1 in 10 (2). Atrial fibrillation is related with expanded rates of death, thromboembolic events, heart failure and hospitalizations, reduced quality of life, reduced exercise capacity, and left ventricular dysfunction (3). It is unfortunately associated with a five-fold elevated stroke risk, besides it is the most common type of arrhythmia (2,4,5). 1Corresponding author: E-mail: mohanadyasir@tu.edu.iq Received: 14/10/2018 Accepted:9 /12/2018 Iraqi Journal of Pharmaceutical Sciences https://doi.org/10.31351/vol28iss1pp101-105 mailto:mohanadyasir@tu.edu.iq Iraqi J Pharm Sci, Vol.28(1) 2019 CHADS2 and CHA2DS2-VASc scores in Iraqi AF patients 102 Identification of numerous stroke risk factors has resulted in development of numerous stroke risk schemes. Artificially most of these schemes have classified risk of stroke into high, moderate, and low risk classes (6). CHADS2 score is the most straightforward risk assessment tool. CHADS2 [cardiac failure, hypertension, age (>75 years), diabetes, stroke (doubled)] risk index, which is a point system, was developed by the AF Investigators and Stroke Prevention in Atrial Fibrillation (SPAF) Investigators criteria (7). A newly adjusted scheme that was recommended by European Society of Cardiology (ESC) is CHA2DS2-VASc [cardiac failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled), vascular disease, age 65–74, and sex category (female)], that is also a point system (8). According to the guidelines of the American College of Cardiology (ACC) and the Heart Rhythm Society (HRS) in collaboration with the American Heart Association (AHA) issued in 2014 patients are classified into low (score = 0), intermediate (score =1), and high-risk (score ≥2) groups for a stroke based on their CHADS2 scores. The same categorization also applies to CHA2DS2-VASc (9). For the most of AF patients, the backbones of treatment to decrease stroke risk are antithrombotic medicines (antiplatelet and anticoagulants). The effect of these medicines in decreasing stroke risk is well established. Aspirin and oral anticoagulants (OACs) are usually suggested for preventing AF patients from developing stroke (10). The current study was designed to assess the status of CHADS2 and CHA2DS2-VASc scores in predicting risk of stroke in Iraqi patients with AF, as well as, to report the status of stroke prevention in these patients with aspirin or warfarin in relation to these scores. Subjects, materials, and methods This prospective cross-sectional study was carried out at Tikrit, Samarra, Sharqat, Baquba, and AL-Numaan general hospitals from July 2017 to October 2017. The study protocol was approved by the local ethics committee in the College of Medicine, Tikrit University, Iraq, with verbal informed consent from patients. Inclusion criteria involved any patient who introduced to intensive care unit with documented symptoms of AF (chest pain, palpitation, etc.) at admission and any of the following stroke risk factors: an age of ≥75 years, a previous stroke or transient ischemic attack, diabetes mellitus (DM), recognized peripheral arterial disease (PAD), hypertension, or a left ventricle ejection fraction of 35 – 45% or less. Exclusion criteria involve inadequate data, renal failure, and recent symptoms of bleeding. Information on demographic characteristics was obtained through patient interview. Types and family history of AF and the presence of comorbidities including coronary artery disease (CAD), hypertension, DM, and heart failure were reported with the aid of patient's specialist. Data were collected via face to face structured interview. Each patient was given explanation about the purpose of study in details and confidentiality was ensured. For each patient enrolled, CHADS2 score was calculated by assigning 1 point for cardiac failure, age >75 years, DM, and hypertension and 2 points for a prior stroke, while CHA2DS2-VASc score was calculated by assigning 1 point for female gender, cardiac failure, age of 65 – 74 years, DM, hypertension, vascular disease (complex aortic plaque, myocardial infarction, and PAD; including amputation because of PAD, prior revascularization, or angiographic evidence of PAD) and 2 points for a previous stroke and age 75 years. The objective of stroke prevention determination focused on the current antiplatelets and oral anticoagulant therapy that was offered by the specialist to these patients at the time of hospital discharge. Therefore, results regarding this issue reported how many patients were receiving aspirin and how many patients were receiving warfarin at time of discharged. Statistical analysis was made using the Microsoft excel 2010, and continuous variable are expressed as mean ± standard deviation. Results One hundred patients were participated in this study (20 participants from each hospital), 48 were men and 52 were women. Their mean age was 62.56 ± 14.36 years. Current smoking was reported in 42 patients, while the remaining patients were nonsmokers. Permanent type of AF (abnormal heart rhythm can't be restored) was reported in 32 patients followed by paroxysmal type (symptoms reported occasionally) that was reported in 27 patients, while persistent type (symptoms don't go back to normal on their own and treatment with electrical shock or medications are required) was occurred in 26 patients. Only 15 patients were diagnosed to have long-standing persistent type (AF is continuous and lasts longer than 12 months) of AF. Figure 1 summarizes these data. Figure (1) Types of AF recorded in this study. The most common symptom that was associated with AF and reported by all patients was palpitations. Other symptoms reported were chest Iraqi J Pharm Sci, Vol.28(1) 2019 CHADS2 and CHA2DS2-VASc scores in Iraqi AF patients 103 pain, weakness, lightheadedness, and shortness of breath. Many of these symptoms concomitantly occurred in the same patient. Figure 2 summarizes all these data. Figure (2) Symptoms of AF reported in this study. Many of these symptoms concomitantly occurred in the same patient Patient comorbidities are demonstrated in figure 3. Hypertension was the most prevalent chronic illness (89% of patients) followed by ischemic heart disease, heart failure, PAD, DM and prior stroke attack. Many of these comorbidities concomitantly occurred in the same patient Figure (3) Comorbidities reported in this study. Many of these comorbidities concomitantly occurred in the same patient. Figure 4 shows CHADS2 and CHA2DS2- VASc scores level of utilization in patients enrolled in this study. Unfortunately, these scores were often neglected for these patients and clinicians did not use/rely on these scores. Figure (4) Utilization of CHADS2 and CHA2DS2- VASc scores in this study. Average scores of CHADS2 and CHA2DS2- VASc in this study were 2.34 ± 1.39 and 4.1 ± 2.05, respectively. CHADS2 score categorized 5% of patients as low risk (score=0), 26% as intermediate risk (score=1), and 69% as high risk (score ≥2). On the other hand, CHA2DS2-VASc score categorized 0% of patients as low risk (score=0), 10% as intermediate risk (score=1) and 90% as high risk (score ≥2). Distribution of these scores in patients is demonstrated in Figure 5. Figure (5) Distribution of CHADS2 and CHA2DS2- VASc scores in this study. Figure 6 represents the antithrombotic medications that had being given for these patients at hospital discharge in relation to CHADS2 score. At score zero, 3 and 2 patients were received aspirin and warfarin respectively. At score one, 24 and 2 patients were received aspirin and warfarin respectively, while at score two and greater, 56 and 12 patients were received aspirin and warfarin respectively. Figure (6) Antithrombotic medications that had being given for patients at hospital discharge in relation to CHADS2 score. Figure 7 represents the antithrombotic medications that had being given for these patients at hospital discharge in relation to CHA2DS2-VASc score. No patients were present at score zero. At score one, 6 and 4 patients were received aspirin and warfarin respectively. At score two and greater, 78 and 12 patients were received aspirin and warfarin respectively. Iraqi J Pharm Sci, Vol.28(1) 2019 CHADS2 and CHA2DS2-VASc scores in Iraqi AF patients 104 Figure (7) Antithrombotic medication that had being given for patients at hospital discharge in relation to CHA2DS2-VASc score. Discussion Atrial fibrillation is a common type of arrhythmia that can elevate the risk of stroke by five- fold. OACs and aspirin can diminish stroke risk by 64% and 22%, respectively (11). Despite the fact that OACs treatment is more effective than aspirin at preventing ischemic stroke, its use is offset by an elevated risk of hemorrhage. Hence, the initiation of OACs treatment needs recognizing patients in whom ischemic stroke risk without anticoagulant agents is adequately high to outweigh an elevated risk of major extracranial and intracranial hemorrhage related to OACs treatment (12). As shown in figure 1, permanent type of AF was the most common as presented in 32% of patients followed by paroxysmal (occasional) type that was reported in 27% of patients, persistent type was occurred in 26% of patients, and only 15% patients were diagnosed to have long-standing persistent type of AF. In study of Coppens et al., 52% of patients had permanent AF and 28% had paroxysmal AF, while 19% had persistent AF (12). As shown in figure 2, the most common symptom that was associated with AF and reported by all patients was palpitations. Other symptoms were chest pain, weakness, lightheadedness, and shortness of breath respectively. In comparison, the chief complaints that were reported by Barrett et al. involved palpitations in 41% of patients, chest pain 16%, dyspnea 12%, tachycardia 13%, and syncope in 3% of patients (13). As shown in figure 3, hypertension was the most prevalent chronic illness reported in this study as 89% of patients had it followed by ischemic heart disease, heart failure, PAD, DM and prior stroke attack respectively. In a study of Mason et al., hypertension was recorded in 56% of the patients followed by cardiovascular diseases (PAD and CAD), DM and heart failure respectively (14). All these differences may be attributed mainly to different ethnic groups. As shown in figure 4, application of CHADS2 and CHA2DS2-VASc scores, unfortunately, was often neglected for Iraqi patients with AF. Although the CHADS2 score has been available for many years and is simple to calculate, it does not include several important risk factors and suffers from important limitations (9). For example, a substantial portion of patients are classified as moderate risk, and it is uncertain whether antiplatelet or anticoagulant therapy should be recommended for those patients. Furthermore, the scale ignores some potential risk factors for thromboembolism (15). CHA2DS2-VASc score overcame many of the limitations of the CHADS2 score including its ability to reliably identify “truly low risk” patients, who could be managed with no antithrombotic therapy. Therefore, the CHA2DS2- VASc score is now recommended in recent guidelines instead of the CHADS2 score for stroke assessment in patients with AF (9). As shown in figure 6 and 7, aspirin was the most prescribing antithrombotic agent for Iraqi AF patients regardless to CHADS2 and CHA2DS2- VASc scores. The Main reason for this strategy is to minimize the risk of bleeding that is related to warfarin treatment as the physicians realize that international normalized ratio (INR) cannot be easily titrated. Generally, aspirin is recommended for CHADS2 score = 0, and oral anticoagulant is highly recommended for a score of ≥ 2, while either aspirin or oral anticoagulant is considered suitable for patients with intermediate-risk at a score =1 (16). On the other hand, the ESC guidelines recommend OACs for a CHA2DS2-VASc score ≥ 2 and aspirin or OACs for a score = 1, with OACs “preferred” and for CHA2DS2-VASc score = 0 no therapy or aspirin (no therapy preferred) (14). Completely all guidelines recommend that any patient with CHADS2 score of ≥ 2 should receive an OAC treatment as the ischemic stroke risk outweighs the elevated risk of bleeding that induced by OAC treatment. Management recommendations were unchanged regardless of CHA2DS2-VASc score (12). Although OACs have numerous therapeutic benefits, they have certain risks: major bleeding risk that associates with warfarin treatment is expected to be at (1% – 3%) per year, and may be as high as 7% in elderly AF patients per year (17). A meta-analysis trial reported that OACs therapy had a relative risk (RR) reduction of 62% (95% CI, 0.48 – 0.72) as compared with placebo or usual care. On the other hand, some trials have compared warfarin with aspirin, and a meta- analysis reports that warfarin has the ability to reduce the risk of stroke (RR reduction, 36%; 95% CI, 0.14 – 0.52). However, warfarin benefit is usually associated with an elevated rate of hemorrhage risk. Comparing with aspirin, a meta- analysis reported that warfarin had a risk for intracranial hemorrhage (RR, 2.1; 95% CI, 1.0-4.6) and a double risk for a major extracranial hemorrhage (RR, 2.0; 95% CI, 1.2 – 3.4; absolute risk rise, 0.2% per year) (18). Iraqi J Pharm Sci, Vol.28(1) 2019 CHADS2 and CHA2DS2-VASc scores in Iraqi AF patients 105 This study had several limitations. First, this study was limited by its small sample size from few hospitals. Second, it examined patients at only one point in time and patient’s risk scores may change over time. Third, it examined the hypothetical effect of these scores and cannot make determination as to which scoring system is best. Conclusion CHADS2 and CHA2DS2-VASc scores were often neglected in assessing Iraqi AF patients in hospitals; in addition to that, aspirin is still widely used as a strategy to minimize stroke risk in patients with AF regardless to these scores. Therefore, it will be important to determine by a randomized trial whether the use of antiplatelets and/or OACs in relation to these scores will result in improved outcomes, without increased morbidity/mortality due to bleeding complications. Acknowledgements Deep thanks to pharmacist Omer Muhammad Hamad, Ali Muhanad Ali, Wathiq Adil Mahmood, Ahmed Muhammad Hussein, and Husham Ataa Faris for their valuable efforts and assistance in accomplishing this study. References 1. Gutierrez C and Blanchard DG. Diagnosis and Treatment of Atrial Fibrillation. Am Fam Physician. 2016; 94(6): 442-52. 2. Barra S and Fynn S. Untreated atrial fibrillation in the United Kingdom: Understanding the barriers and treatment options. J Saudi Heart Assoc. 2015; 27(1): 31-43. 3. Atouni M, Gunda S, and Lakkireddy D. Left atrial appendage closure is preferred to chronic warfarin therapy: The pro prospective. In: Controversies in electrophysiology. Daoud E and Weiss R (Eds.). 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