著者

Daisuke Fukamachi Hiroyuki Hao Suguru Migita Naotaka Akutsu Yoshiaki Kusumi Yasuo Okumura Atsushi Hirayama

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.1, no.11, pp.538-539, 2019-11-08 (Released:2019-11-08)

著者

Atsushi Hirayama Shizuya Yamashita Andrea Ruzza Hyoe Inomata Marcoli Cyrille Chen Lu Andrew W. Hamer Masayuki Yoshida Arihiro Kiyosue Tamio Teramoto

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.83, no.5, pp.971-977, 2019-04-25 (Released:2019-04-25)

参考文献数

11

被引用文献数

1

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Background: Treatment with evolocumab reduces mean low-density lipoprotein cholesterol (LDL-C) up to 75% and cardiovascular events by 16% in the first year and 25% thereafter. Methods and Results: Japanese patients with hypercholesterolemia enrolled in the parent YUKAWA-1-2 studies could enroll, once eligible, in the OSLER studies (n=556). OSLER re-randomized patients 2:1 to evolocumab plus standard of care (SOC; evolocumab+SOC) or SOC alone for 1 year; after year 1, patients could enter the all-evolocumab+SOC open-label extension of OSLER. Patients received evolocumab+SOC from the 2nd year through up to 5 years. Long-term efficacy and safety, including antidrug antibodies, were evaluated. Of 556 patients, 532 continued to the all-evolocumab+SOC extension: mean (standard deviation [SD]) age 61 (10) years, 39% female. A total of 91% of 532 patients completed the studies. Mean (SD) LDL-C change from parent-study baseline with evolocumab from a mean (SD) baseline of 142.3 (21.3) and 105.0 (31.1) mg/dL in OSLER-1 and OSLER-2, respectively, was maintained through the end of the study: −58.0% (19.1%) at year 5 in OSLER-1, −62.7% (25.6%) at year 3 in OSLER-2. The overall safety profile of the evolocumab+SOC periods was similar to that of the year-1 controlled period. Antidrug antibodies were detected transiently in 3 patients. No neutralizing antibodies were detected. Conclusions: Japanese patients who continued evolocumab+SOC for up to 5 years experienced sustained high LDL-C level reduction. Long-term evolocumab+SOC exposure showed no new safety signals.

著者

Yasuo Okumura Katsuaki Yokoyama Naoya Matsumoto Eizo Tachibana Keiichiro Kuronuma Koji Oiwa Michiaki Matsumoto Toshiaki Kojima Shoji Hanada Kazumiki Nomoto Ken Arima Fumiyuki Takahashi Tomobumi Kotani Yukitoshi Ikeya Seiji Fukushima Satoru Itou Kunio Kondo Masaaki Chiku Yasumi Ohno Motoyuki Onikura Atsushi Hirayama for the SAKURA AF Registry Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.10, pp.2500-2509, 2018-09-25 (Released:2018-09-25)

参考文献数

20

被引用文献数

55

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Background: Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times and rates, are lacking. Methods and Results: The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5–43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users. Conclusions: A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.

著者

Mariko Harada-Shiba Junya Ako Atsushi Hirayama Masato Nakamura Atsushi Nohara Kayoko Sato Yoshitaka Murakami Ryusuke Koshida Asuka Ozaki Hidenori Arai

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.8, pp.1201-1212, 2022-08-01 (Released:2022-08-01)

参考文献数

32

被引用文献数

3 7

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Aim: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered “standard of care,” including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. Methods: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant.Results: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants of LDLR, LDLRAP1, or PCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of the LDLR gene and the PCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH.Conclusions: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.

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

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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

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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

Yuki Saito Mahoto Kato Koichi Nagashima Koyuru Monno Yoshihiro Aizawa Yasuo Okumura Naoki Matsumoto Mitsuhiko Moriyama Atsushi Hirayama

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.7, pp.1822-1829, 2018-06-25 (Released:2018-06-25)

参考文献数

29

被引用文献数

18 45

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Background:Acute decompensated heart failure (ADHF) is often accompanied by liver congestion through increased right atrial pressure (RAP). Liver stiffness (LS) assessed non-invasively using transient elastography is related to increased RAP and liver congestion in patients with general HF. We investigated the relationship of LS with clinical and echocardiographic variables and outcomes in patients with ADHF.Methods and Results:The subjects were 105 patients with ADHF admitted to hospital between October 2016 and June 2017. Patients were divided into 2 groups based on median LS at admission (low LS <8.8 kPa [n=52] vs. high LS ≥8.8 kPa [n=53]). Death from cardiovascular disease and readmission for HF were primary endpoints. Total bilirubin and γ-glutamyl transpeptidase levels, MELD-XI score, diameters of the inferior vena cava and right ventricle, and severity of tricuspid regurgitation were greater in the high LS group (all P<0.05). During a median (interquartile range) follow-up period of 153 (83–231) days, cardiac events occurred in 29 patients (54%) in the high LS group and in 13 (25%) in the low LS group (P=0.001). After adjusting for variables that influence organ congestion, a high LS ≥8.8 kPa was still significantly associated with cardiac events (all P<0.05).Conclusions:Increased LS measured by transient elastography reflects RAP elevation, hepatic congestion, and hepatic dysfunction. LS upon admission may be a useful prognostic marker in patients with ADHF.

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

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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

Masato Nakamura Kazushige Kadota Koichi Nakao Yoshihisa Nakagawa Junya Shite Hiroyoshi Yokoi Ken Kozuma Kengo Tanabe Takashi Akasaka Toshiro Shinke Takafumi Ueno Atsushi Hirayama Shiro Uemura Atsushi Harada Takeshi Kuroda Atsushi Takita Raisuke Iijima Yoshitaka Murakami Shigeru Saito

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-20-1058, (Released:2021-02-11)

参考文献数

20

被引用文献数

9

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Background:Outcomes with prasugrel single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT) in Japanese percutaneous coronary intervention (PCI) patients with high bleeding risk (HBR) are currently unknown.Methods and Results:Data from 1,173 SAPT and 2,535 DAPT patients from the PENDULUM mono and PENDULUM registry studies (respective median DAPT durations: 108 vs. 312 days) were compared. The adjusted cumulative incidence of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding from 1 to 12 months after PCI (primary endpoint) was 2.8% (95% confidence interval [CI], 1.9–4.2) and 4.1% (95% CI, 3.3–5.1), respectively (hazard ratio [HR], 0.69; 95% CI, 0.45–1.06; P=0.090). The adjusted cumulative incidences of BARC 2, 3, or 5 bleeding from 0 to 12 months after PCI (secondary endpoint) were 3.8% (95% CI, 2.7–5.3) and 5.6% (95% CI, 4.7–6.7), respectively (HR, 0.68; 95% CI, 0.47–0.98; P=0.039). There was no significant difference in major adverse cardiac and cerebrovascular events (MACCE) from 1 to 12 months after PCI (HR, 0.93; 95% CI, 0.63–1.37; P=0.696) and at 12 months after PCI (HR, 0.85; 95% CI, 0.61–1.19; P=0.348) between the groups.Conclusions:Prasugrel SAPT may reduce BARC 2, 3, or 5 bleeding, without increasing MACCE, in Japanese patients with HBR.

著者

Yasuo Okumura Katsuaki Yokoyama Naoya Matsumoto Eizo Tachibana Keiichiro Kuronuma Koji Oiwa Michiaki Matsumoto Toshiaki Kojima Shoji Hanada Kazumiki Nomoto Ken Arima Fumiyuki Takahashi Tomobumi Kotani Yukitoshi Ikeya Seiji Fukushima Satoru Itou Kunio Kondo Masaaki Chiku Yasumi Ohno Motoyuki Onikura Atsushi Hirayama for the SAKURA AF Registry Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-18-0535, (Released:2018-08-04)

参考文献数

20

被引用文献数

55

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Background:Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times and rates, are lacking.Methods and Results:The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5–43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users.Conclusions:A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.

著者

Kazuhisa Kodama Sei Komatsu Yasunori Ueda Tadateru Takayama Jyunji Yajima Shinsuke Nanto Hiroshi Matsuoka Satoshi Saito Atsushi Hirayama

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.74, no.9, pp.1922-1928, 2010 (Released:2010-08-25)

参考文献数

31

被引用文献数

29 51

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Background: Few studies have serially monitored the change of coronary plaque after statin therapy using multiple plaque imaging modalities. Methods and Results: A prospective open-label trial was performed to assess coronary plaque regression and stabilization following 52 weeks of pitavastatin treatment (2 mg/day). Coronary segments that included the most diseased plaque of 90 patients determined on angioscopy were analyzed using intravascular ultrasound (IVUS). The yellow grade of each plaque of 46 patients who had matched angioscopy and IVUS data was evaluated on angioscopy. Low-density lipoprotein-cholesterol (LDL-C) was reduced 34.5% (145.0±24.0 mg/dl to 93.6±22.6 mg/dl, P<0.001), and high-density lipoprotein cholesterol increased 17.8% (44.9±11.1 mg/dl to 51.9±11.7 mg/dl, P<0.001). Yellow grade decreased (2.9±0.8 to 2.6±0.7, P=0.040) during 52 weeks. The reduction of yellow grade was not correlated with the LDL-C level at 52 weeks or its change. The change of yellow grade was inversely correlated with maximum yellow grade at baseline. Percent atheroma volume on IVUS did not change during 52 weeks, but its change for 52 weeks was significantly correlated with LDL-C level at 52 weeks (Spearman's rank correlation coefficient 0.312, P=0.035). Conclusions: Fixed dose pitavastatin stabilized vulnerable coronary plaques by the reduction of yellow grade without significant reduction of plaque volume. The stabilization and regression of atherosclerotic plaques by statin may differ, but both nonetheless contribute to the reduction of cardiovascular events (UMIN Clinical Trials Registry UMIN000001107).  (Circ J 2010; 74: 1922 - 1928)

著者

Atsushi Hirayama Satoshi Saito Yasunori Ueda Tadateru Takayama Junko Honye Sei Komatsu Osamu Yamaguchi Yuxin Li Junji Yajima Shinsuke Nanto Kenji Takazawa Kazuhisa Kodama

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.73, no.4, pp.718-725, 2009 (Released:2009-03-25)

参考文献数

27

被引用文献数

32 83

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Background: The aim of this study was to elucidate the time course of atorvastatin-induced changes in vulnerable plaque using angioscopy and intravascular ultrasound (IVUS). Methods and Results: Fifty-seven hypercholesterolemic patients with coronary artery disease (CAD) were treated with atorvastatin (10-20 mg/day) for 80 weeks and then coronary plaques were evaluated with angioscopy and IVUS. Angioscopic images were classified into 6 grades (0-5) based on yellow color intensity. A 20-mm segment containing angioscopically-identified yellow plaque was also examined by IVUS to measure atheroma volume. The mean angioscopic grade of 58 yellow plaques significantly decreased from 1.5 (95% confidence interval [CI] 1.2 to 1.8) to 1.1 (95%CI 0.9 to 1.3, P=0.012) at week 28 and 1.2 (95%CI 0.9 to 1.4, P=0.024) at week 80. Mean volume of 30 lesions, including the 58 yellow plaques, significantly reduced -8.3% (95%CI -11.5 to -5.2) at week 28 (P<0.001 for baseline vs week 28) and -17.8% (95%CI -23.9 to -11.8) at week 80 (P<0.001 for baseline vs week 80). Conclusions: In patients with CAD treated with atorvastatin, serial analysis with angioscopy demonstrated early loss of yellow color in plaques, and IVUS volumetric analysis showed subsequent plaque regression. Both changes possibly indicate reduction of plaque vulnerability in an additive manner. (Circ J 2009; 73: 718 - 725)

著者

Tadateru Takayama Takafumi Hiro Masakazu Yamagishi Hiroyuki Daida Atsushi Hirayama Satoshi Saito Tetsu Yamaguchi Masunori Matsuzaki The COSMOS Investigators

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.73, no.11, pp.2110-2117, 2009 (Released:2009-10-23)

参考文献数

29

被引用文献数

109 153

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Background: It has been suggested that intensive lipid-lowering therapy using statins significantly decreases atheromatous plaque volume. The effect of rosuvastatin on plaque volume in patients with stable coronary artery disease (CAD), including those receiving prior lipid-lowering therapy, was examined in the present study. Methods and Results: A 76-week open-label trial was performed at 37 centers in Japan. Eligible patients began treatment with rosuvastatin 2.5 mg/day, which could be increased at 4-week intervals to ≤20 mg/day. A total of 214 patients underwent intravascular ultrasound (IVUS) at baseline; 126 patients had analyzable IVUS images at the end of the study. The change in the serum low-density lipoprotein-cholesterol level from baseline to end of follow-up was -38.6 ±16.9%, whereas that of high-density lipoprotein-cholesterol was +19.8 ±22.9% (both P<0.0001). Percent change of plaque volume, the primary endpoint, was -5.1 ±14.1% (P<0.0001). Conclusions: Rosuvastatin exerted significant regression of coronary plaque volume in Japanese patients with stable CAD, including those who had previously used other lipid-lowering drugs. Rosuvastatin might be useful in the setting of secondary prevention in patients with stable CAD. (Circ J 2009; 73: 2110-2117)

著者

Atsushi Hirayama Narimon Honarpour Masayuki Yoshida Shizuya Yamashita Fannie Huang Scott M. Wasserman Tamio Teramoto

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-14-0130, (Released:2014-03-21)

参考文献数

38

被引用文献数

30 83 26

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Background: YUKAWA is a 12-week, randomized, double-blind, placebocontrolled, phase 2 study evaluating the efficacy and safety of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Methods and Results: 310 eligible patients receiving stable statin (±ezetimibe) therapy were randomized to 1 of 6 treatments: placebo every 2 weeks (Q2W) or monthly (QM), evolocumab 70mg or 140mg Q2W, or evolocumab 280mg or 420mg QM. The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) measured by preparative ultracentrifugation (UC). Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C <1.8mmol/L. Mean (SD) age was 62 (10) years; 37% were female; and the mean (SD) baseline LDL-C was 3.7 (0.5) mmol/L (by UC). Mean (SE) changes vs. placebo in LDL-C were greatest in the high-dose groups: −68.6 (3.0) % and −63.9 (3.2) % with 140mg Q2W and 420mg QM dosing, respectively. Up to 96% of evolocumab-treated patients achieved LDL-C <1.8mmol/L. Adverse events (AEs) were more frequent in evolocumab (51%) vs. placebo (38%) patients; 4 patients taking evolocumab discontinued treatment because of an AE. There were no significant differences in AE rates based on dose or dose frequency. Conclusions: In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy, evolocumab significantly reduced LDL-C and was well tolerated during this 12-week study.

著者

Shinobu Imai Fumio Saito Hidehito Takase Mitsunobu Enomoto Hiroshi Aoyama Satoshi Yamaji Katsuaki Yokoyama Hiroshi Yagi Toshio Kushiro Atsushi Hirayama

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.72, no.5, pp.709-715, 2008 (Released:2008-04-25)

参考文献数

21

被引用文献数

6 11

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Background It has been reported that bepridil is as good as amiodarone in converting persistent atrial fibrillation (AF) to sinus rhythm (SR). The conversion effect of bepridil alone is not always satisfactory, however. The efficacy of pharmacological cardioversion by the combination of bepridil and a class Ic antiarrhythmic drug for persistent AF is studied. Methods and Results The participants comprised 37 consecutive patients in whom pharmacological cardioversion was conducted to treat persistent AF (duration 22.5±29.6 months). Each patient first received a class Ia or Ic antiarrhythmic drug, then bepridil alone, then a combined therapy of bepridil at 200 mg/day with a class Ic antiarrhythmic drug at a routine dose. Unaccompanied use of any of the antiarrhythmic drugs achieved pharmacological cardioversion in 14 (38%) of the 37 patients (single therapy group), whereas SR was restored by combination of bepridil and a class Ic antiarrhythmic drug in 22 (combined therapy group) of the remaining 23 patients. The duration of AF was significantly longer in the combined therapy group than in the single therapy group (28.3±31.0 vs 7.3±4.1 months). Conclusion Combined therapy of bepridil and a class Ic antiarrhythmic drug is efficient for pharmacological cardioversion of refractory long-lasting persistent AF. (Circ J 2008; 72: 709 - 715)

著者

Shigemasa Tani Atsuhiko Takahashi Ken Nagao Atsushi Hirayama

出版者

一般社団法人 インターナショナル・ハート・ジャーナル刊行会

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

pp.14-243, (Released:2015-04-23)

被引用文献数

1 23

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We investigated the relationships between the ratio of serum n-3 polyunsaturated fatty acids (n-3PUFAs: eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) to n-6PUFA (arachidonic acid [AA]) and the prevalence of coronary artery disease (CAD), and assessed the association of the ratio of serum n-3 to n-6 PUFAs with atherosclerosis-related markers.This study was designed as a hospital-based cross-sectional study of 649 consecutive outpatients who had undergone regular examinations between April 2009 and October 2009. We divided the patients into 5 groups based on the quintiles of the EPA/AA ratio or quintiles of the DHA/AA ratio to determine independent factors for the prevalence of CAD.In multivariate logistic regression analyses after adjustment for coronary risk factors and serum n-3PUFAs levels to minimize confounding factors to the extent possible because the serum levels of EPA and DHA showed a strong correlation (r = 0.812, P < 0.0001), the group with the highest EPA/AA ratio had a lower probability of CAD prevalence (odds ratio: 0.328, 95% confidence interval: 0.113 to 0.956, P = 0.041), but this was not true for the DHA/AA ratio. Multivariate analysis showed an increase in the EPA/AA ratio, but not in the DHA/AA ratio, was associated with effects on atherosclerosis-related markers, especially triglyceride-rich lipoproteins, high-density lipoprotein cholesterol (HDL-C) containing apolipoprotein A-1, and leukocyte count in an anti-atherogenic direction.The results suggest a higher EPA/AA ratio, but not a higher DHA/AA ratio, might be associated with a lower prevalence of CAD and improvements of triglyceride metabolism and HDL metabolism, and systemic inflammation.

著者

Naoki Sato Wataru Takahashi Atsushi Hirayama Masayoshi Ajioka Naoto Takahashi Kaoru Okishige XingLi Wang Akio Maki Hideki Maruyama Ursula Ebinger Masayuki Yamaguchi Yinuo Pang Hiroki Matsumoto Masatoshi Kawana

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-15-0227, (Released:2015-04-24)

参考文献数

27

被引用文献数

4 16

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Background:Serelaxin, a recombinant form of human relaxin-2, is in development for treating acute heart failure (AHF) and a Phase II study in Japanese AHF patients was conducted.Methods and Results:A randomized, double-blind, placebo-controlled study of serelaxin at 10 and 30 µg·kg–1·day–1continuous intravenous infusion for up to 48 h, added to standard care for Japanese AHF patients. Primary endpoints were adverse events (AEs) through Day 5, serious AEs (SAEs) through Day 14, and serelaxin pharmacokinetics. Secondary endpoints included changes in systolic blood pressure (SBP) and cardiorenal biomarkers. A total of 46 patients received the study drug and were followed for 60 days. The observed AE profile was comparable between the groups, with no AEs of concern. Dose-dependent increase in the serum concentration of serelaxin was observed across the 2 dose rates of serelaxin. A greater reduction in SBP was observed with serelaxin 30 µg·kg–1·day–1vs. placebo (–7.7 [–16.4, 1.0] mmHg). A greater reduction in NT-proBNP was noted with serelaxin (–50.8% and –54.9% for 10 and 30 µg·kg–1·day–1, respectively at Day 2).Conclusions:Serelaxin was well tolerated in this study with Japanese AHF patients, with no AEs of concern and favorable beneficial trends on efficacy. These findings support further evaluation of serelaxin 30 µg·kg–1·day–1in this patient population.

著者

Yoshiki YUI Tetsuya SUMIYOSHI Kazuhisa KODAMA Atsushi HIRAYAMA Hiroshi NONOGI Katsuo KANMATSUSE Hideki ORIGASA Osamu IIMURA Masao ISHII Takao SARUTA Kikuo ARAKAWA Saichi HOSODA Chuichi KAWAI JMIC-B Study Group

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.27, no.7, pp.449-456, 2004 (Released:2004-08-07)

参考文献数

19

被引用文献数

21 27

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We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme (ACE) inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions), and the secondary endpoints were a composite of other events (cerebrovascular accidents, worsening of renal dysfunction, non-cardiovascular events, and total mortality). The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group (n =199) and the ACE inhibitor group (n =173) in diabetic patients: 15.08% vs. 15.03%, relative risk 1.06, p =0.838. Also in nondiabetic patients, no significant difference was observed between the former (n =629) and the latter (n =649): 13.67% vs. 12.33%, relative risk 1.04, p =0.792. Similar results were obtained for the incidence of the secondary endpoints: in diabetic patients, 5.03% vs. 5.20%, relative risk 0.89, p =0.799; in nondiabetic patients, 2.70% vs. 2.47%, relative risk 1.07, p =0.842. Achieved blood pressure levels were 138/76 and 136/77 mmHg in the nifedipine group and 140/78 and 138/79 mmHg in the ACE inhibitor group in diabetic and nondiabetic patients, respectively. This study showed that nifedipine retard was as effective as ACE inhibitors in reducing the incidence of cardiac events in extremely high-risk hypertensive patients with complications of diabetes and coronary artery disease. (Hypertens Res 2004; 27: 449-456)

著者

Yoshiki YUI Tetsuya SUMIYOSHI Kazuhisa KODAMA Atsushi HIRAYAMA Hiroshi NONOGI Katsuo KANMATSUSE Hideki ORIGASA Osamu IIMURA Masao ISHII Takao SARUTA Kikuo ARAKAWA Saichi HOSODA Chuichi KAWAI JMIC-B Study Group

出版者

日本高血圧学会

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.27, no.3, pp.181-191, 2004 (Released:2004-10-19)

参考文献数

29

被引用文献数

70 103

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The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease. The subjects were 1,650 outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery disease. There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group. The patients were randomized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions). The primary endpoint occurred in 116 patients (14.0%) from the nifedipine retard group and 106 patients (12.9%) from the angiotensin converting enzyme inhibitor group (relative risk, 1.05; 95% confidence interval, 0.81-1.37; p =0.75). In the Kaplan-Meier estimates, there were no significant differences between the two groups (log-rank test: p =0.86). The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies. Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality. (Hypertens Res 2004; 27: 181-191)

著者

Ichiro Watanabe Yasuo Okumura Rikitake Kogawa Naoko Sasaki Kimie Ohkubo Masayoshi Kofune Koichi Nagashima Kazumasa Sonoda Hiroaki Mano Atsushi Hirayama

出版者

一般社団法人 インターナショナル・ハート・ジャーナル刊行会

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.53, no.6, pp.375-382, 2012 (Released:2012-12-18)

参考文献数

22

被引用文献数

1 4

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Catheter ablation of persistent/long-persistent atrial fibrillation (AF) has been shown to be less effective by pulmonary vein isolation (PVI) and additional left atrial (LA) complex fractionated atrial electrograms and long linear lesions are often required. Recent reports have demonstrated right atrial (RA) ablation increases the success rate of maintaining sinus rhythm in persistent/long-persistent AF. The aim of this study was to investigate whether effective RA linear lesions can terminate AF and render it noninducible in a canine model of rapid atrial pacing-induced sustained AF. Sustained AF was induced by rapid atrial pacing in 20 dogs. AF duration was 21-126 days (median, 50 days). Four RA linear lesions (superior vena cava-inferior vena cava, septal line, transverse line, and cavo-tricuspid line) were created with the use of 1 of 3 different ablation catheters (large-tip [8-mm tip], coil-tip, and cooled-tip catheters). AF was terminated with the large-tip catheter in 4/7 dogs (1 dog died of ventricular fibrillation [VF]), with the coil-tip catheter in 3/7 dogs (1 dog died of VF), and with the cooled-tip catheter in 1/6 dogs. In 6 dogs in which AF could not be terminated acutely by RA ablation, AF terminated spontaneously at 7-78 days (median, 14 days) after ablation. RA linear ablation terminated AF with limited success in our dog model of rapid atrial pacing-induced AF, but late AF termination was noted in the surviving dogs. Therefore, RA linear lesions in addition to the PVI and LA lesions may have additional effects on the catheter ablation for the persistent AF.