2014 年 78 巻 7 号 p. 1567-1568
In this issue of the Journal, Okumura et al validate the CHA2DS2-Vasc score using the modified CHA2DS2-Vasc (mCHA2DS2-Vasc) score in Japanese patients with non-valvular atrial fibrillation (NVAF) enrolled in the J-RHYTHM Registry1 and report that the mCHA2DS2-Vasc score was useful for identifying patients at truly low risk of thromboembolism. This result appears to assist with treating NVAF patients in the clinic because it suggests that we do not need to administer warfarin any more to NVAF patients with a mCHA2DS2-Vasc score of 0. A similar result had already been reported in a nationwide cohort study conducted in Denmark.2 NVAF patients with a mCHA2DS2-Vasc score of 0 accounted for 7% of the J-Rhythm Registry created by Japanese cardiology specialists, and those with a CHA2DS2-Vasc score of 0 accounted for 4.1% of the Fushimi AF registry, an urban community-based registry in Japan.1,3 When such patients still hope to receive anticoagulation, we may consider administration of a non-VKA oral anticoagulants (NOAC) with a much lower incidence of intracranial bleeding than warfarin.4–8 It has also been reported that the hematomas that can arise because of acute intracranial bleeding during dabigatran treatment seem to remain small to moderate in size, resistant to expansion, and thus manageable.9
Article p 1593
Is Female Sex Not an Independent Risk Factor for Thromboembolism?The authors found no significant difference in the event rates of the non-warfarin and warfarin groups with an mCHA2DS2-Vasc score of 0 or when the score excluded the risk of female sex; therefore, they concluded that female sex might be excluded as a risk from the score.10 Mikkelsen et al analyzed 87,202 AF patients from national Danish registries and found that female sex was only associated with an increased risk of stroke for AF patients aged ≥75 years, and suggested that female sex should not be automatically included as an independent stroke/thromboembolic risk factor in guidelines or in the CHA2DS2-Vasc score without careful prior consideration of age <65 years and the lone AF criterion.10 Inoue et al studied the effect of sex on prognosis in 7,406 Japanese NVAF patients from the J-Rhythm Registry and demonstrated that female sex was not a risk factor for thromboembolic events.11 In the first place, how does female sex contribute to intracardiac thrombus formation? Other items in the CHA2DS2-Vasc score, including congestive heart failure, hypertension, advanced age, diabetes mellitus, vascular disease and stroke, transient ischemic attack, or systemic embolism, are considered to be strongly related to intracardiac thrombus formation because of enhanced blood coagulability based on stasis of blood flow and systemic arteriosclerosis, or as a result of intracardiac thrombus formation (Figure). However, no mechanisms appear to link female sex and intracardiac thrombus formation. According to several studies’ results, as mentioned earlier, it seems reasonable to not take female sex into account in stroke risk stratification of NVAF patients.
Relationship between each item of the CHA2DS2 -VASc score and intracardiac thrombus formation. Vascular disease includes myocardial infarction, aortic plaque, and peripheral artery disease. TIA, transient ischemic attack; TE, thromboembolism.
Although the CHADS2 score is used for guidelines in Canada and Japan and has several merits, including a simple and convenient risk stratification method and its use in several major clinical trials comparing warfarin and NOAC, its weakness is that vascular disease and age from 65 to 74 years are not considered.12,13 On the other hand, the CHA2DS2-Vasc score is applied in Europe and the USA and can be used to evaluate age from 65 to 74 years and vascular disease as important independent risk factors; however, it is slightly complicated and includes “female sex”, not an independent risk factor for stroke, which seems to be a weakness of this scoring method14,15 (Table). Therefore, it seems that both scoring methods have strengths and weaknesses. When we use the CHADS2 score, we need to evaluate age 65–74 years and vascular disease separately; when we use the CHA2DS2-Vasc score, we should not take the score of “female sex” into account.
ESC guidelines for the management of AF (2012) |
CHA2DS2-VASc score |
Congestive heart failure |
Hypertension |
Age ≥75 years |
Diabetes mellitus |
Stroke/TIA/TE |
Vascular disease |
Age 65–74 years |
Female |
Japanese guideline for pharmacotherapy for AF (2013) |
CHADS2 score |
Congestive heart failure |
Hypertension |
Age ≥75 years |
Diabetes mellitus |
Stroke/TIA |
Other risk factors |
Vascular disease |
Age 65–74 years |
Cardiomyopathy |
AF, atrial fibrillation; TE, thromboembolism; TIA, transient ischemic attack.
The Japanese guideline for pharmacotherapy for AF adopted the CHADS2 score and other risk factors for vascular disease, age from 65 to 74 years, and cardiomyopathy (Table, Figure).13 Cardiomyopathy has been reported as a risk factor for stroke in NVAF patients by several studies in Japan.13 Thus, this guideline is thought to be well constructed for NVAF risk stratification based on the advantages and disadvantages of the CHADS2 and CHA2DS2-Vasc scores.
Conflict of Interest: Lecture fees from Nippon Boehringer Ingelheim, Bayer Yakuhin and Bristol-Myers Squibb.