Target International Normalized Ratio Values for Preventing Thromboembolic and Hemorrhagic Events in Japanese Patients With Non-Valvular Atrial Fibrillation

Robust evidence exists on the efficacy of traditional anticoagulant oral therapy in the prevention of thrombo-embolic risk in patients with non valvular atrial fibrillation, but fears and concerns of hemorrhagic events for the physicians and logistic difficulties related to the periodic International Normalized Ratio evaluation for the patients are at the basis of a noticeable under-utilization of the therapy with vitamin K antagonists in the real world. Stratification of the hemorrhagic risk has, thus, particular importance; for this objective we may use now several score system, among whom the more suggested is the HASBLED, with the principal aim to select and trait modifiable risk factors for bleeding. These score systems have been evaluated in some recent clinical trials. During the last years, a number of national and international guidelines on the prevention of the thrombo-embolic risk in patients with non valvular atrial fibrillation have been updated. These guidelines, generally, recommend the use of the CHA2DS2VaSC score for the evaluation of the thrombo-embolick risk, and of the HAS-BLED score for the evaluation of the hemorrhagic one. The consequent risk stratification is fundamental as a clinical guide for the use of oral anticoagulant therapy.

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Thromboembolic and hemorrhagic risk stratification in patients with atrial fibrillation. Part I: the thromboembolic risk

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2013.80 ◽

2015 ◽

Vol 80 (2) ◽

Author(s):

Maurizio Giuseppe Abrignani ◽

Furio Colivicchi

Keyword(s):

Atrial Fibrillation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vascular Diseases ◽

International Normalized Ratio ◽

Cerebrovascular Events ◽

Hemorrhagic Events ◽

Hemorrhagic Risk ◽

Risk Patients ◽

Embolic Risk

Atrial fibrillation, whose prevalence is in constant increase, is associated to a noticeably greater thrombo-embolic risk. Various associated factors, such as older age, arterial hypertension, heart failure, previous cerebrovascular events (stroke and transient ischemic attacks), diabetes mellitus, female sex and vascular diseases determine a further increase of the risk of stroke in patients with atrial fibrillation. Robust evidence exists on the efficacy of traditional anticoagulant oral therapy in the prevention of thrombo-embolic risk in these patients, but fears and concerns of hemorrhagic events for the physicians and the logistic difficulties related to the periodic International Normalized Ratio evaluation for the patients are at the basis of a noticeable under-utilization of the therapy with vitamin K antagonists in the real world. Stratification of the thrombo-embolic risk has thus particular importance; for this scope we may use now score systems as CHA2DS2 and, above all, CHA2DS2-Vasc, that allows the identification of truly low risk patients, which do not require an antithrombotic treatment. Novel oral anticoagulants, lastly, will help physicians in order to obtain a better management of trombo-embolic risk in atrial fibrillation.

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Effects of the quality of warfarin therapy on the development of ischemic and hemorrhagic events in elderly Japanese patients with nonvalvular atrial fibrillation

Nosotchu ◽

10.3995/jstroke.10455 ◽

2017 ◽

Vol 39 (4) ◽

pp. 261-267

Author(s):

Kazuo Nakajima ◽

Motoji Naka ◽

Osamu Nishiyama ◽

Miki Takahama ◽

Eita Nishimori ◽

...

Keyword(s):

Atrial Fibrillation ◽

Warfarin Therapy ◽

Japanese Patients ◽

Nonvalvular Atrial Fibrillation ◽

Hemorrhagic Events ◽

Elderly Japanese ◽

Elderly Japanese Patients

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Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

Cerebrovascular Diseases ◽

10.1159/000445723 ◽

2016 ◽

Vol 42 (3-4) ◽

pp. 196-204 ◽

Cited By ~ 12

Author(s):

Asako Nakamura ◽

Junya Kuroda ◽

Tetsuro Ago ◽

Jun Hata ◽

Ryu Matsuo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Japanese Patients ◽

International Normalized Ratio ◽

Stroke Registry ◽

Underlying Causes ◽

Therapeutic Doses ◽

Medication Status

Background: Oral anticoagulants (OACs) reduce the incidence of embolic events associated with non-valvular atrial fibrillation (NVAF); however, ischemic stroke can still occur in such patients. Although there are various causes of ischemic stroke in patients with NVAF, their medication status at onset has scarcely been studied. This retrospective study aimed to determine the underlying causes of ischemic stroke in patients with NVAF in relation to pre-stroke anticoagulation. Methods: Among Japanese patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to May 2013, 1,302 patients with NVAF who had been hospitalized within 24 h of onset were included in this study, and their backgrounds, pre-stroke use of OACs and prothrombin time-international normalized ratio (PT-INR) on admission were investigated. Strokes were regarded as being non-cardioembolic (CE) type when causes other than NVAF had been identified. The sub-therapeutic range (TR) for warfarin was defined according to Japanese guidelines for pharmacotherapy of atrial fibrillation. Results: Atrial fibrillation had been diagnosed prior to onset of stroke in 704 of 1,302 patients (54%). However, it had not been detected before or on admission, but identified later during hospitalization in 270 patients (21%). Of the patients who had atrial fibrillation on admission but had not been diagnosed as having it, 108 (8%) had not received any medication before onset of stroke and 220 (17%) had received medications other than OACs. OACs had been administered to 415 (59%) of the patients with known atrial fibrillation. The proportion of pre-stroke CHADS2 or CHA2DS2-VASc scores ≥1 ranged from 93 to 99% depending on whether atrial fibrillation had been diagnosed or anticoagulation therapy administered before stroke onset. The PT-INR was in the sub-TR on admission in 283 of 399 patients (71%) receiving warfarin. Male sex, smoking and previous stroke were more prevalent in patients with values within or over the TR of PT-INR than in those in the sub-TR. Non-CE stroke was more prevalent in patients with values above the lower therapeutic limit of the recommended PT-INR than in those in the sub-TR (p < 0.001). The number of CE strokes was much smaller in patients with high admission PT-INR values; this was not observed for non-CE ischemic strokes (p < 0.001). Conclusions: In the clinical setting, under-diagnosis, underuse and sub-therapeutic doses of OACs are major causes of ischemic stroke in patients with NVAF. However, non-CE ischemic strokes may develop in patients receiving therapeutic doses of warfarin.

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Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656065 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0845-0848 ◽

Cited By ~ 23

Author(s):

B G Koefoed ◽

C Feddersen ◽

A L Gulløv ◽

P Petersen

Keyword(s):

Atrial Fibrillation ◽

International Normalized Ratio ◽

Coagulation System ◽

Nonvalvular Atrial Fibrillation ◽

Treatment Groups ◽

Prothrombin Fragment ◽

Conventional Dose ◽

Dose Warfarin ◽

Significant Difference ◽

Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

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