3 3 * ** Key Words : non valvular atrial fibrillation, novel oral anticoagulant, warfarin, CHADS score, HAS BLED score 3 9 96 04 5 35 NVAF 9 NVAF I NVAF. CHADS CHADS 5 Table 4 06 4 warfarin Table 0 warfarin CHADS warfarin warfarin Fig. 65 74 3 Fig.. CHADS VASc CHADS VASc 8 0 9 Table 4 CHADS 65 75 CHADS 0 0 0.78 warfarin 0.6.0 5 0 warfarin Table 3 3 CHADS 3 CHADS Prevention of Stroke in Patients with Non valvular Atrial Fibrillation. Masahiro YASAKA : Department of Cerebrovascular Medicine, National Hospital Organization Kyushu Medical Center Vol. 3 No. 3 04 9
Table CHADS and CHADS VASc scores CHADSCHADS VASc Congestive heart failure Congestive heart failure/left ventricular dysfunction / Hypertension Hypertension Age 75 yrs 75 Age 75 yrs 75 Diabetes mellitus Diabetes mellitus Stroke/transient ischemic attack / Stroke/transient ischemic attack/te // Vascular disease prior myocardial infarction, peripheral artery disease or aortic plaque Age 65 74 yrs 65 74 Sex category i.e. female gender Table CHADS and CHADS VASc scores CHADSCHADS VASc CHADS CHADS VASc Gage BF : JAMA 00 ; 85 : 864 870 Lip GY : Chest 00 ; 37 : 63 7 0 6 0 0 9 0 warfarin 0 65 74 0 3 CHADS CHADS VAScESC European Society of Cardi ology II HAS BLED Pisters HAS BLED Table 300 ESC 6 8 HAS BLEDHypertension Abnormal renal and liver function Stroke Bleeding Labile INRs Elderly Drugs and alcohol Table 3 7 HAS BLED Abnormal renal and liver function Drugs and alcohol NSAIDs Vol. 3 No. 3 04 9
心房細動に伴う脳梗塞の予防 Fig. Guideline for pharmacotherapy of atrial fibrillation from the Japanese Circulation Society. quoted from reference 3 * 血管疾患とは心筋梗塞の既往 大動脈プラーク および末梢動脈疾患などをさす * 人工弁とは機械弁 生体弁をともに含む *3 04 年 7 月の時点では保険適応未承認 もしくはアルコール依存症で 点ずつのため 全部で 9 点満点 Table 3 HAS-BLED score HAS-BLED スコア である 頭文字 臨床像 ポイント クは増加する 大出血リスクは 0 点で低リスク 年間大出血 H 高血圧 発症リスク 点で中等度リスク 4 3 点以 A 腎 肝機能障害 各 点 S 脳卒中 B 出血 3 L 不安定な国際標準比 INR 4 導が大切である 抗血栓療法の併用をできるだけ避けること E 高齢者 65 歳より高齢 も求められる HAS-BLED スコアが高い場合に 抗血栓療 D 薬剤 アルコール 各 点 5 HAS-BLED スコア 0 9 点 が上昇すると大出血リス 上で高リスク 4 6 である HAS-BLED スコアが 3 点以上で高い場合は 大出血のリ スク管理が極めて重要である 頭蓋内出血のリスクである血 圧や血糖管理 過度のアルコール摂取を避けることや禁煙指 法を弱く行うべきとの主張があるが この対応は慎重であら 9 ねばならない まず 抗血栓療法を弱く行って十分な効果が 収縮期血圧 60mmHg 腎機能障害 慢性透析や腎移植 血清クレアチニン 00μmol/ l.6mg/dl 以上 肝機能異常 慢性肝障害 肝硬変など または検査値異常 ビリ ルビン値 正常上限 倍 AST/ALT/ALP 正常上限 3 倍 3 過去の出血歴かつ / または出血傾向 出血素因 貧血など 4 不安定な / 高値 INR または TTR 治療時間域 60 未満 5 抗血小板薬や NSAIDs 併用 またはアルコール依存症 確保できるというエビデンスが乏しいこと HAS-BLED の 項目の多くは CHADS スコアや CADS-Vasc スコアと重複 しており HAS-BLED スコアが高い症例は CHADS スコア や CADS-VASc スコアも高く 脳梗塞や全身塞栓症のハイ リスク症例だからである したがって 抗血栓療法を弱めに 行うよりも まず 大出血や頭蓋内出血のリスク管理を徹底 神経治療 Vol. 3 No. 3 04 93
Table 4 Features of each novel oral anticoagulant IIa Xa Xa Xa 4 9 3 8 5 0 4 Tmax 0.5 4 4 6.5 67 86 49 6 35 9 95 87 40.0 58.9 CYP3A4/J CYP3A4 CYP3A4 80 33 66 5 50 Yes No No No / & / III Warfarin. novel oral anticoagulants NOAC warfarin heparin 3 NOAC warfarin 9 NOAC warfarin 04 03 Fig. CHADS 3 warfarin CHDS dabigatran apixaban warfa rin dabigatran apixaban warfarin dabigatran apixaban CHADS dabigatran apixaban 9, 4, 5 NOAC Rivaroxaban edoxaban III CHADS CHADS. Warfarin Warfarin NOAC warfarin NOAC PT INR IV NOAC dabigatran rivaroxaban apixaban Table 4 6. Dabigatran DabigatranCHADS APTT 9, 5, 7, 8. Rivaroxaban Rivaroxaban Vol. 3 No. 3 04 94
0, 8, 9 CHADS 3. Apixaban Apixaban CHADS APTT 4. Edoxaban Edoxaban 3 PT INR NOAC warfarin NOAC warfarin COI Gage BF, Waterman AD, Shannon W et al : Validation of clini cal classification schemes for predicting stroke. Resulte from the National Regisry of Atrial Fibrillation. JAMA 85 : 864 870, 00 Ogawa S, Hori M : Urgent statement on antithrombotic thera py of atrial fibrillation. Circ J 75 : 79 7, 0 3 Olesen JB, Lip GY, Hansen ML et al : Validation of risk stratifi cation schemes for predicting stroke and thromboembolism in patients with atrial fibrillation : nationwide cohort study. BMJ 34 : d4. doi: 0.36/bmj.d4., 0 4 Lip GY, Nieuwlaat R, Pisters R et al : Refining clinical risk stratification for predicting stroke and thrombo embolism in atrial fibrillation using a novel risk factor based approach : the euro heart survey on atrial fibrillation. Chest 37 : 63 7, 00 5 Toyoda K, Yasaka M, Iwade K et al ; Bleeding with Antithrom botic Therapy BAT Study Group : Dual antithrombotic ther apy increases severe bleeding events in patients with stroke and cardiovascular disease : a prospective, multicenter, obser vational study. Stroke 39 : 740 745, 008 6 Pisters R, Lane DA, Nieuwlaat R et al : A novel user friendly score HAS BLED to assess year risk of major bleeding in patients with atrial fibrillation : the Euro Heart Survey. Chest 38 : 093 00, 00 7 European Heart Rhythm Association, European Association for Cardio Thoracic Surgery : Guidelines for the management of atrial fibrillation : The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology ESC. Europ Heart J 3 : 369 49, 00 8 Lip GY, Frison L, Halperin JL et al : Comparative validation of a novel risk score for predicting bleeding risk in anticoagulat ed patients with atrial fibrillation. J Am Coll Cardiol 57 : 73 80, 0 9 Connolly SJ, Ezekowitz MD, Yusuf S et al ; RE LY Steering Committee and Investigators : Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 36 : 39 5, 009 and Erratum in : N Engl J Med 363 : 877, 00 0 Patel MR, Mahaffey KW, Garg J et al : ROCKET AF Investiga tors : Rivaroxaban versus warfarin in nonvalvular atrial fibril lation. N Engl J Med 365 : 883 89, 0 Granger CB, Alexander JH, McMurray JJ et al : ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365 : 98 99, 0 Giugliano RP, Ruff CT, Braunwald E et al : Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369 : 093 04, 03 3 0 03 htp://www.j circ.or.jp/guideline/ pdf/jcs 03_inoue_h.pdf 04 7 6 4 Hart RG, Diener HC, Yang S et al : Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfa rin or dabigatran : The RE LY trial. Stroke 43 : 5 57, 0 5 Oldgren J, Alings M, Darius H et al : Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabiga tran or warfarin in relation to the CHADS score : a subgroup analysis of the RE LY trial. Ann Intern Med 55 : 660 667, 0 6 Ogawa S, Koretsune Y, Yasaka M et al : Antithrombotic thera py in atrial fibrillation : evaluation and positioning of new oral anticoagulant agents. Circ J 75 : 539 547, 0 7 dabigatran 7 : 3 8, 0 8 Yasaka M : Current strategy for anticoagulation therapy for pa tients with non valvular atrial fibrillation. J Arrhythmia 8 : 34 33, 0 9 Hori M, Matsumoto M, Tanahashi N et al : Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation. Circ J 76 : 04, 0 Vol. 3 No. 3 04 95
Prevention of Stroke in Patients with Non valvular Atrial Fibrillation Masahiro YASAKA Department of Cerebrovascular Medicine, National Hospital Organization Kyushu Medical Center Non valvular atrial fibrillation NVAF is the most common cardiac source of emboli in cardioembolic stroke which occupies 0 to 35% of acute brain infarction in Japan. In order to prevent the cardioembolic stroke, nock out type brain infarction, in NVAF patients, warfarin treat ment has been spread since guideline of the anticoagula tion for prevention of stroke in NVAF was issued. However, it has many limitations that make its use difficult. About half of patients with NVAF, who were indicated to warfarin treatment, are treated with warfarin. Bleeding complica tions including devastating intracranial hemorrhage has become a big concern during warfarin treatment. Novel oral anticoagulants NOAC are superior to warfarin, be cause they are easy to use, their effect in preventing isch emic stroke is higher than or as high as warfarin, their inci dence of major hemorrhage is lower than or as low as warfarin, and their incidence of intracranial hemorrhage is much lower than warfarin. CHADS and CHADS Vasc scores are used for stratification of stroke and HAS BLED score are for major hemorrhage during warfarin treatment. In this review, current strategies of anticoagulation for pre vention of stroke in NVAF are discussed. Vol. 3 No. 3 04 96