著者
Nobuhiro Murata 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 Itoh 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.83, no.4, pp.727-735, 2019-03-25 (Released:2019-03-25)
参考文献数
27
被引用文献数
10

Background: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over- and under-dosing are lacking in Japan. Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under- and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard- and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081). Conclusions: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.
著者
Nobuhiro Murata 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 Itoh 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-18-0991, (Released:2019-02-05)
参考文献数
27
被引用文献数
10

Background: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over- and under-dosing are lacking in Japan. Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under- and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard- and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081). Conclusions: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.
著者
Atsushi Hirayama Norio Tanahashi Hiroyuki Daida Naoki Ishiguro Motohiko Chachin Toshihiko Sugioka Shinichi Kawai on behalf of all ACCEPT study investigators in Japan
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-1573, (Released:2013-10-22)
参考文献数
35
被引用文献数
4 13

Background: A prospective, 3-year comparative observational study compared the risk of cardiovascular events in patients with osteoarthritis or rheumatoid arthritis prescribed celecoxib or a nonsteroidal antiinflammatory drug (NSAID). Methods and Results: Patients prescribed celecoxib (n=5,470) or NSAIDs (n=5,059) between November 1, 2007, and July 31, 2008 in 1,084 hospitals and clinics in Japan were eligible for safety analysis. Mean (standard deviation) observation for the celecoxib group was 716 (420) days and 692 (426) days for the NSAID group (P=0.004). Composite I (adjudicated cardiovascular adverse events of myocardial infarction, angina pectoris, heart failure, cerebral infarction, cerebral hemorrhage) number of events (percentage) and rate/1,000 person years was 66 (1.2%) and 6.2 (10,745 person years), respectively, for the celecoxib and 65 (1.3%) and 6.8 (9,601 person years) for the NSAID (P=0.58) groups. Composite II (all cardiovascular events) number of events (percentage) and rate/1,000 person years was 79 (1.4%) and 7.4, respectively, for the celecoxib and 84 (1.7%) and 8.8 for the NSAID (P=0.26) group. Adjusted Cox hazards ratio (95% confidence interval) was 0.89 (0.63–1.27; P=0.52) for Composite I, 0.87 (0.63–1.19; P=0.39) for Composite II and 1.03 (0.75–1.41; P=0.87) for death from all causes. Conclusions: After adjustment for confounding variables, celecoxib was not associated with an increase of cardiovascular risk in comparison with nonselective NSAID in Japanese patients with rheumatoid arthritis or osteoarthritis in an observational setting.
著者
Atsushi Hirayama Norio Tanahashi Hiroyuki Daida Naoki Ishiguro Motohiko Chachin Toshihiko Sugioka Shinichi Kawai on behalf of all ACCEPT study investigators in Japan
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.78, no.1, pp.194-205, 2014 (Released:2013-12-25)
参考文献数
35
被引用文献数
4 13

Background: A prospective, 3-year comparative observational study compared the risk of cardiovascular events in patients with osteoarthritis or rheumatoid arthritis prescribed celecoxib or a nonsteroidal antiinflammatory drug (NSAID). Methods and Results: Patients prescribed celecoxib (n=5,470) or NSAIDs (n=5,059) between November 1, 2007, and July 31, 2008 in 1,084 hospitals and clinics in Japan were eligible for safety analysis. Mean (standard deviation) observation for the celecoxib group was 716 (420) days and 692 (426) days for the NSAID group (P=0.004). Composite I (adjudicated cardiovascular adverse events of myocardial infarction, angina pectoris, heart failure, cerebral infarction, cerebral hemorrhage) number of events (percentage) and rate/1,000 person years was 66 (1.2%) and 6.2 (10,745 person years), respectively, for the celecoxib and 65 (1.3%) and 6.8 (9,601 person years) for the NSAID (P=0.58) groups. Composite II (all cardiovascular events) number of events (percentage) and rate/1,000 person years was 79 (1.4%) and 7.4, respectively, for the celecoxib and 84 (1.7%) and 8.8 for the NSAID (P=0.26) group. Adjusted Cox hazards ratio (95% confidence interval) was 0.89 (0.63–1.27; P=0.52) for Composite I, 0.87 (0.63–1.19; P=0.39) for Composite II and 1.03 (0.75–1.41; P=0.87) for death from all causes. Conclusions: After adjustment for confounding variables, celecoxib was not associated with an increase of cardiovascular risk in comparison with nonselective NSAID in Japanese patients with rheumatoid arthritis or osteoarthritis in an observational setting.  (Circ J 2014; 78: 194–205)
著者
Yuma Hamanaka Yohei Sotomi Akio Hirata Tomoaki Kobayashi Yasuhiro Ichibori Nobuhiko Makino Takaharu Hayashi Yasushi Sakata Atsushi Hirayama Yoshiharu Higuchi
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-19-1006, (Released:2020-02-11)
参考文献数
21
被引用文献数
3

Background:This study investigated the impact of systemic inflammation on bleeding risk in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOAC).Methods and Results:We conducted a single-center prospective registry of 2,216 NVAF patients treated with DOAC: the DIRECT registry (UMIN000033283). High-sensitivity C-reactive protein (hsCRP) was measured ≤3 months before (pre-DOAC hsCRP) and 6±3 months after initiation of DOAC (post-DOAC hsCRP). Multivariate logistic regression model was used to assess the influence of systemic inflammation and conventional bleeding risk factors on major bleeding according to International Society on Thrombosis and Haemostasis criteria. Based on the findings, we created a new bleeding risk assessment score: the ORBIT-i score, which included post-DOAC hsCRP >0.100 mg/dL and all components of the ORBIT score. A total of 1,848 patients had both pre- and post-DOAC hsCRP data (follow-up duration, 460±388 days). Post-DOAC hsCRP was associated with major bleeding (OR, 2.770; 95% CI: 1.687–4.548, P<0.001). Patients with post-DOAC hsCRP >0.100 mg/dL more frequently had major bleeding than those without (log-rank test, P<0.001). ORBIT-i score had the highest C-index of 0.711 (95% CI, 0.654–0.769) compared with the ORBIT and HAS-BLED scores.Conclusions:Persistent systemic inflammation was associated with major bleeding risk. ORBIT-i score had a higher discriminative performance compared with the conventional bleeding risk scores.
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

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
27

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
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
27

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 41

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 77

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
109 131

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 61 26

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 12

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 15

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 15

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 24

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 91

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)