著者
Satoshi Ogawa Yukihiro Koretsune Masahiro Yasaka Yoshifusa Aizawa Hirotsugu Atarashi Hiroshi Inoue Shiro Kamakura Koichiro Kumagai Hideo Mitamura Ken Okumura Kaoru Sugi Takeshi Yamashita
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.75, no.7, pp.1539-1547, 2011 (Released:2011-06-24)
参考文献数
59
被引用文献数
33 43

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for stroke. For more than 60 years, warfarin has been the only approved anticoagulant for prevention of stroke in patients with AF. Although highly effective, it has many limitations that make its use difficult. Therefore, several novel anticoagulants are under development to overcome the limitations of warfarin, and some of these have entered phase III clinical trials. Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. It has also been approved in the United States and Japan for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In this review, the mechanism of action and pharmacological properties of new anticoagulants are described in detail, and the correct use of dabigatran in clinical practice is discussed. (Circ J 2011; 75: 1539-1547)
著者
Masaharu Akao Hiroshi Inoue Takeshi Yamashita Hirotsugu Atarashi Takanori Ikeda Yukihiro Koretsune Ken Okumura Shinya Suzuki Hiroyuki Tsutsui Kazunori Toyoda Atsushi Hirayama Masahiro Yasaka Takenori Yamaguchi Satoshi Teramukai Tetsuya Kimura Yoshiyuki Morishima Atsushi Takita Wataru Shimizu
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-23-0143, (Released:2023-07-21)
参考文献数
21
被引用文献数
1

Background: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death.Conclusions: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.
著者
Masahiro YASAKA Kazuo MINEMATSU Takenori YAMAGUCHI
出版者
一般社団法人 日本内科学会
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
vol.40, no.12, pp.1183-1188, 2001 (Released:2006-03-27)
参考文献数
21
被引用文献数
118 175

Objective To determine optimal intensity of international normalized ratio (INR) of warfarin therapy for the prevention of ischemic events in patients with non-valvular atrial fibrillation (NVAF), we evaluated the risk of severe recurrent stroke, systemic embolism and major hemorrhagic complications according to INR and age. Methods We carried out the National Cardiovascular Center (NCVC) NVAF Secondary Prevention Study and analyzed data with those of Japanese Nonvaluvular Atrial Fibrillation-embolism Secondary Prevention Cooperative Study to elucidate relationships of major stroke and hemorrhage with INR and age. In both studies, all patients with cardioembolic stroke were given warfarin, monitored with INR every month, and followed up for primary endpoints of stroke and embolism to other parts of the body, and for secondary endpoints of major hemorrhagic complications requiring blood transfusion or hospitalization. We regarded ischemic stroke with NIH stroke scale (NIHSS) score >10 or systemic embolism as a major ischemic event and ischemic stroke with NIHSS score <10 as a minor ischemic event. There were 203 patients enrolled in total (152 men and 51 women). We investigated the relationship of occurrence of the events with INR and age, and calculated the incidence rates of major and minor ischemic events and major hemorrhagic events. Results During the mean follow-up of 653 days, major ischemic stroke and systemic embolism occurred in only 4 patients with INR <1.6, minor ischemic stroke in 10 patients with INR 1.50-2.66, and major hemorrhage in 9 patients with INR 2.30-3.56. Patients with major ischemic or hemorrhagic events were significantly older than those without any events (75±4 years vs. 67±7 years, p<0.001 unpaired t test). Incidence rates of any events at INR ≤1.59, 1.60-1.99, 2.00-2.59 and ≥2.60 were 8.6%, 3.8%, 4.9%, and 25.7%/year, respectively. Conclusions Major ischemic or hemorrhagic events occur often in the elderly NVAF patients, in whom an INR value of between 1.6 and 2.6 seems optimal to prevent such events.(Internal Medicine 40:1183-1188, 2001)
著者
Ken-ichi Hiasa Hidetaka Kaku Goro Kawahara Hiroshi Inoue Takeshi Yamashita Masaharu Akao Hirotsugu Atarashi Takanori Ikeda Yukihiro Koretsune Ken Okumura Wataru Shimizu Kazunori Toyoda Atsushi Hirayama Masahiro Yasaka Takenori Yamaguchi Satoshi Teramukai Tetsuya Kimura Jumpei Kaburagi Atsushi Takita Hiroyuki Tsutsui
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.86, no.2, pp.222-232, 2022-01-25 (Released:2022-01-25)
参考文献数
31
被引用文献数
4

Background:Echocardiographic data on the cardiac structure and function in elderly patients with atrial fibrillation (AF) and heart failure (HF) are limited. This subcohort study of the ANAFIE Registry analyzed echocardiographic parameters to identify cardiac structural and functional characteristics.Methods and Results:Of 32,726 subjects in the ANAFIE population, 1,494 (4.6%) were entered as the echocardiography subcohort. Half of the patients, including those with persistent and permanent AF, older age (≥80 years), and CHADS2score ≥2, had left atrial (LA) volume index ≥48 mL/m2, indicating severe LA enlargement. LA enlargement significantly correlated with impaired LA reservoir function, regardless of age and CHADS2score. Types of AF and rhythm were strongly related to LA volume and reservoir function (P<0.0001). Moderate-to-severe mitral and tricuspid regurgitation were significantly more common, and the early diastolic mitral inflow velocity to mitral annulus velocity ratio was significantly higher among patients with than without HF history (all, P<0.0001).Conclusions:In this subcohort, LA enlargement correlated with impaired LA reservoir function. Elderly patients with non-valvular AF and a history of HF had LA enlargement and dysfunction, increased LV mass index, low LV ejection fraction, and high heart rate.
著者
Takeshi Yamashita Masaharu Akao Hirotsugu Atarashi Takanori Ikeda Yukihiro Koretsune Ken Okumura Wataru Shimizu Shinya Suzuki Hiroyuki Tsutsui Kazunori Toyoda Atsushi Hirayama Masahiro Yasaka Takenori Yamaguchi Satoshi Teramukai Tetsuya Kimura Yoshiyuki Morishima Atsushi Takita Hiroshi Inoue
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-22-0614, (Released:2023-01-17)
参考文献数
26
被引用文献数
3

Background: Previous studies on mortality in atrial fibrillation (AF) included a limited number of elderly patients receiving direct oral anticoagulants (DOACs). This subanalysis of the ANAFIE Registry evaluated 2-year mortality according to causes of death of elderly non-valvular AF (NVAF) patients in the DOAC era.Methods and Results: The ANAFIE Registry was a multicenter prospective observational study. Mean patient age was 81.5 years and 57.3% of patients were male. Of the 32,275 patients completing the study, 2,242 died. The most frequent causes of death were cardiovascular (CV) death (32.4%), followed by infection (17.1%) and malignancy (16.1%). Incidence rates of CV-, malignancy-, and infection-related death were 1.20, 0.60, and 0.63 per 100 person-years, respectively. Patients aged ≥85 years showed increased proportions of non-CV and non-malignancy deaths and a decreased proportion of malignancy deaths compared with patients aged <85 years. The incidence of death due to congestive heart failure/cardiogenic shock, infection, and renal disease was higher in patients aged ≥85 than those aged <85 years. Compared with warfarin, DOACs were associated with a significantly lower risk of death by intracranial hemorrhage, ischemic stroke, and renal disease.Conclusions: This subanalysis described the mortality according to causes of death of Japanese elderly NVAF patients in the DOAC era. Our results imply that a more holistic approach to comorbid conditions and stroke prevention are required in these patients.
著者
Takanori Ikeda Takeshi Yamashita Masaharu Akao Hirotsugu Atarashi Yukihiro Koretsune Ken Okumura Wataru Shimizu Hiroyuki Tsutsui Kazunori Toyoda Atsushi Hirayama Masahiro Yasaka Takenori Yamaguchi Satoshi Teramukai Tetsuya Kimura Jumpei Kaburagi Atsushi Takita Hiroshi Inoue
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.86, no.2, pp.202-210, 2022-01-25 (Released:2022-01-25)
参考文献数
41
被引用文献数
3

Background:Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed.Methods and Results:In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer.Conclusions:Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.
著者
Yohei Mima Yuhei Sangatsuda Masahiro Yasaka Yoshiyuki Wakugawa Shinji Nagata Yasushi Okada
出版者
The Japanese Society of Internal Medicine
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
vol.53, no.21, pp.2523-2527, 2014 (Released:2014-11-01)
参考文献数
10
被引用文献数
10 14

A 75-year-old man with paroxysmal atrial fibrillation developed a traumatic intracranial hemorrhage during warfarin treatment. The administration of warfarin was stopped and rivaroxaban therapy, a novel oral anticoagulant (NOAC), was started. Immediately, his platelet count decreased to 3.7×104 /μL. The platelet count recovered rapidly after cessation of rivaroxaban administration. Development of thrombocytopenia and its rapid recovery was observed again after another administration, and subsequent cessation, of the drug. A diagnosis of rivaroxaban-induced thrombocytopenia was made. The incidence of thrombocytopenia due to NOACs is rare. Careful attention to thrombocytopenia, which is associated with a higher risk for life-threatening bleeding, is therefore necessary during treatment with NOACs.
著者
Yukihiro Koretsune Takeshi Yamashita Tetsuya Kimura Masayuki Fukuzawa Kenji Abe Masahiro Yasaka
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.79, no.7, pp.1486-1495, 2015-06-25 (Released:2015-06-25)
参考文献数
23
被引用文献数
40 54

Background:The short-term safety and plasma concentrations of edoxaban 15 mg once daily in Japanese patients with non-valvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CLCR] ≥15 to <30 ml/min) were compared with those in NVAF patients with normal renal function or mild renal impairment (normal/MiRI; CLCR≥50 ml/min) treated with edoxaban 30 or 60 mg.Methods and Results:In this Phase 3 multicenter open-label 3 parallel-group study, SRI patients received once-daily edoxaban 15 mg (n=50), whereas normal/MiRI patients were randomized to receive either once-daily edoxaban 30 or 60 mg (n=22 and 21, respectively) for 12 weeks. Plasma edoxaban concentrations and biomarkers of blood coagulation and fibrinolysis were measured. Adverse events and thromboembolic events were recorded throughout the study. Rates of any bleeding were comparable between SRI patients receiving edoxaban 15 mg (20.0%) and normal/MiRI patients receiving edoxaban 30 or 60 mg (22.7% and 23.8%, respectively). No major bleeding or thromboembolic events occurred in any treatment group. Similar plasma concentrations and biomarker profiles were observed in SRI patients receiving edoxaban 15 mg and normal/MiRI patients receiving edoxaban 30 or 60 mg.Conclusions:In this 12-week short-term study in Japanese NVAF patients with SRI, edoxaban 15 mg once daily exhibited similar safety, plasma concentration, and biomarker profiles as did the 30-mg and 60-mg doses in patients with normal/MiRI. (Circ J 2015; 79: 1486–1495)