789
Theme Issue Article
1General
Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan; 2University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
Summary Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In 2050, it is estimated that there will be 72 million AF patients in Asia, accounting for almost 2.9 million patients suffering from AF-associated stroke. Asian AF patients share similar risk factor profiles as non-Asians, except that more Asians have a history of previous stroke. Clinical challenges are evident in the field of stroke prevention in AF, amongst Asians. Existing stroke and bleeding risk scores have not been well-validated in Asians. Asians are prone to bleeding when treated with warfarin, and the optimal international normalised ratio (INR) for warfarin use is yet to be determined in Asians, though Asian physicians tend to keep it in a lower range (e.g. INR 1.6–2.6) for elderly patients despite limited evidence to justify this. In general, warfarin is ‘difficult’ to use in Asians due to higher risk of bleeding and Correspondence to: Prof. Chern-En Chiang Division of Cardiology Taipei Veterans General Hospital 201, Section 2, Shih-Pai Road Taipei 112, Taiwan Tel.: +88 6228757774, Fax: +88 6228745422 E-mail: [email protected]
higher stroke rate in Asians than in non-Asians, as shown in randomised controlled trials. Excess of bleeding was not found in Asians when novel oral anticoagulants (NOACs) were used. Besides, the superiority of NOACs to warfarin in reducing thromboembolism was maintained in Asians. Therefore NOACs are preferentially indicated in Asians in terms of both efficacy and safety. Also, some preliminary data suggest that Asian patients with AF might not be the same. Future prospective randomised trials are needed for the selection of NOACs according to different ethnic background.
Keywords Atrial fibrillation, Asians, major bleeding, novel oral anticoagulants, stroke
Received: November 18, 2013 Accepted after major revision: January 16, 2014 Prepublished online: February 6, 2014 doi:10.1160/TH13-11-0948 Thromb Haemost 2014; 111: 789–797
Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.
Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia (1), and carries a four- to five-fold increased risk of stroke. The prevalence of AF is adult Asians is about 1%, lower than that in Caucasians (1–2%) (2, 3). Since Asia is the most populated area in the world, the burden of AF in Asia may actually exceed that in Western countries, and indeed, it has been estimated that in 2050 there will be 72 million AF patients in Asia (4), more than double the combined numbers of patients from Europe and the United States (5, 6). The mean/median CHADS2 (Congestive heart failure, Hypertension, Age, Diabetes, Stroke [double]) scores in recent Asian cohort studies has been around 2.0–2.2 (7-9). Based on known distribution of CHADS2 in these cohorts, the annual risk of stroke would be estimated to be at least 4% (notwithstanding the fact that the CHADS2 is not well validated in Asians). Thus, almost 2.9 million patients will suffer from AF-associated stroke in year 2050 in Asia if no oral anticoagulants (OACs) are given. Thus, this would a © Schattauer 2014
huge medical and economic burden, necessitating a proper action for stroke prevention in AF patients in Asia.
Risk factor profiles Congestive heart failure, hypertension, diabetes, and previous stroke/transient ischaemic attack (TIA) are established risk factors for predicting stroke risk in AF, and are components of the CHADS2 score, which was initially derived from the non-warfarin arms of the historical randomised trials conducted approximately 20 years ago (10). There are no comprehensive prospective direct comparisons of risk factor profiles for AF in Asians versus nonAsians. Data from AF registries and cohort studies, such as the Euro Heart Survey (11), Fushimi AF registry (8), RECORD-AF study (12), RECORD-AF-Asia Pacific registry (13), and REALISE-AF registry (7, 14), or sub-groups of anti-thrombotic trials, such as RE-LY (15, 16), ROCKET AF (17), and ARISTOTLE (18, 19), may provide some important information. About one-third of AF paThrombosis and Haemostasis 111.5/2014
Downloaded by: University of the Sciences in Philadelphia. Copyrighted material.
Chern-En Chiang1; Kang-Ling Wang1; Gregory Y. H. Lip2
New Oral Anticoagulants
Stroke prevention in atrial fibrillation: An Asian perspective
Chiang et al. Stroke prevention in atrial fibrillation in Asia
tients have congestive heart failure, which was slightly more common in non-Asians (except in the RE-LY trial) (▶ Figure 1 A). Almost 60 to 90% of patients have hypertension, again more common in non-Asians (except in the REALISE-AF registry) (▶ Figure 1 B). Diabetes mellitus, on the other hand, is generally more common in Asians (except in the ROCKET AF trial and the ARISTOTLE trial) (▶ Figure 1 C). The major difference is the prevalence of previous stroke or TIA, which is much higher in Asians (▶ Figure 1 D). Therefore, the risk factor profiles in Asians are similar to non-Asians, except that the percentage of patients with previous stroke is much higher in Asians.
Asian AF patients have a high risk of stroke The CHADS2 score has been used to predict annual stroke risk in patients with non-valvular AF, by identifying ‘high risk’ patients who would be candidates for anticoagulation (10). This scoring system has been validated in various studies from non-Asian patients (10, 20). However, data in Asians are more limited (4), and only small scaled studies have been performed (21).
The CHADS2 score has various limitations (22), being derived from the historical trial cohorts that only randomised
Theme Issue Article
1General
Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan; 2University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
Summary Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In 2050, it is estimated that there will be 72 million AF patients in Asia, accounting for almost 2.9 million patients suffering from AF-associated stroke. Asian AF patients share similar risk factor profiles as non-Asians, except that more Asians have a history of previous stroke. Clinical challenges are evident in the field of stroke prevention in AF, amongst Asians. Existing stroke and bleeding risk scores have not been well-validated in Asians. Asians are prone to bleeding when treated with warfarin, and the optimal international normalised ratio (INR) for warfarin use is yet to be determined in Asians, though Asian physicians tend to keep it in a lower range (e.g. INR 1.6–2.6) for elderly patients despite limited evidence to justify this. In general, warfarin is ‘difficult’ to use in Asians due to higher risk of bleeding and Correspondence to: Prof. Chern-En Chiang Division of Cardiology Taipei Veterans General Hospital 201, Section 2, Shih-Pai Road Taipei 112, Taiwan Tel.: +88 6228757774, Fax: +88 6228745422 E-mail: [email protected]
higher stroke rate in Asians than in non-Asians, as shown in randomised controlled trials. Excess of bleeding was not found in Asians when novel oral anticoagulants (NOACs) were used. Besides, the superiority of NOACs to warfarin in reducing thromboembolism was maintained in Asians. Therefore NOACs are preferentially indicated in Asians in terms of both efficacy and safety. Also, some preliminary data suggest that Asian patients with AF might not be the same. Future prospective randomised trials are needed for the selection of NOACs according to different ethnic background.
Keywords Atrial fibrillation, Asians, major bleeding, novel oral anticoagulants, stroke
Received: November 18, 2013 Accepted after major revision: January 16, 2014 Prepublished online: February 6, 2014 doi:10.1160/TH13-11-0948 Thromb Haemost 2014; 111: 789–797
Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.
Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia (1), and carries a four- to five-fold increased risk of stroke. The prevalence of AF is adult Asians is about 1%, lower than that in Caucasians (1–2%) (2, 3). Since Asia is the most populated area in the world, the burden of AF in Asia may actually exceed that in Western countries, and indeed, it has been estimated that in 2050 there will be 72 million AF patients in Asia (4), more than double the combined numbers of patients from Europe and the United States (5, 6). The mean/median CHADS2 (Congestive heart failure, Hypertension, Age, Diabetes, Stroke [double]) scores in recent Asian cohort studies has been around 2.0–2.2 (7-9). Based on known distribution of CHADS2 in these cohorts, the annual risk of stroke would be estimated to be at least 4% (notwithstanding the fact that the CHADS2 is not well validated in Asians). Thus, almost 2.9 million patients will suffer from AF-associated stroke in year 2050 in Asia if no oral anticoagulants (OACs) are given. Thus, this would a © Schattauer 2014
huge medical and economic burden, necessitating a proper action for stroke prevention in AF patients in Asia.
Risk factor profiles Congestive heart failure, hypertension, diabetes, and previous stroke/transient ischaemic attack (TIA) are established risk factors for predicting stroke risk in AF, and are components of the CHADS2 score, which was initially derived from the non-warfarin arms of the historical randomised trials conducted approximately 20 years ago (10). There are no comprehensive prospective direct comparisons of risk factor profiles for AF in Asians versus nonAsians. Data from AF registries and cohort studies, such as the Euro Heart Survey (11), Fushimi AF registry (8), RECORD-AF study (12), RECORD-AF-Asia Pacific registry (13), and REALISE-AF registry (7, 14), or sub-groups of anti-thrombotic trials, such as RE-LY (15, 16), ROCKET AF (17), and ARISTOTLE (18, 19), may provide some important information. About one-third of AF paThrombosis and Haemostasis 111.5/2014
Downloaded by: University of the Sciences in Philadelphia. Copyrighted material.
Chern-En Chiang1; Kang-Ling Wang1; Gregory Y. H. Lip2
New Oral Anticoagulants
Stroke prevention in atrial fibrillation: An Asian perspective
Chiang et al. Stroke prevention in atrial fibrillation in Asia
tients have congestive heart failure, which was slightly more common in non-Asians (except in the RE-LY trial) (▶ Figure 1 A). Almost 60 to 90% of patients have hypertension, again more common in non-Asians (except in the REALISE-AF registry) (▶ Figure 1 B). Diabetes mellitus, on the other hand, is generally more common in Asians (except in the ROCKET AF trial and the ARISTOTLE trial) (▶ Figure 1 C). The major difference is the prevalence of previous stroke or TIA, which is much higher in Asians (▶ Figure 1 D). Therefore, the risk factor profiles in Asians are similar to non-Asians, except that the percentage of patients with previous stroke is much higher in Asians.
Asian AF patients have a high risk of stroke The CHADS2 score has been used to predict annual stroke risk in patients with non-valvular AF, by identifying ‘high risk’ patients who would be candidates for anticoagulation (10). This scoring system has been validated in various studies from non-Asian patients (10, 20). However, data in Asians are more limited (4), and only small scaled studies have been performed (21).
The CHADS2 score has various limitations (22), being derived from the historical trial cohorts that only randomised
