著者
Hiroyuki Tsutsui Hiroshi Ito Masafumi Kitakaze Issei Komuro Toyoaki Murohara Tohru Izumi Kenji Sunagawa Yoshio Yasumura Masafumi Yano Kazuhiro Yamamoto Tsutomu Yoshikawa Takayoshi Tsutamoto Junwei Zhang Akifumi Okayama Yoshihiko Ichikawa Kazuhiro Kanmuri Masunori Matsuzaki for the J-EMPHASIS-HF Study Group
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-0323, (Released:2017-08-19)
参考文献数
19
被引用文献数
22

Background:The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction (HFrEF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. However, similar efficacy and safety have not been established in Japanese patients. We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter, randomized, double-blind placebo-controlled outcome study (ClinicalTrials.gov Identifier: NCT01115855). The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of <1 for the hazard ratio.Methods and Results:HFrEF patients with NYHA functional class II–IV and an EF ≤35% received eplerenone (n=111) or placebo (n=110) on top of standard therapy for at least 12 months. The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF. The primary endpoint occurred in 29.7% of patients in the eplerenone group vs. 32.7% in the placebo group [hazard ratio=0.85 (95% CI: 0.53–1.36)]. Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone. A total of 17 patients (15.3%) in the eplerenone group and 10 patients (9.1%) in the placebo group died. Adverse events, including hyperkalemia, were similar between the groups.Conclusions:Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study.
著者
Hiroyuki Tsutsui Hiroshi Ito Masafumi Kitakaze Issei Komuro Toyoaki Murohara Tohru Izumi Kenji Sunagawa Yoshio Yasumura Masafumi Yano Kazuhiro Yamamoto Tsutomu Yoshikawa Takayoshi Tsutamoto Junwei Zhang Akifumi Okayama Yoshihiko Ichikawa Kazuhiro Kanmuri Masunori Matsuzaki for the J-EMPHASIS-HF Study Group
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.1, pp.148-158, 2017-12-25 (Released:2017-12-25)
参考文献数
19
被引用文献数
22

Background:The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction (HFrEF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. However, similar efficacy and safety have not been established in Japanese patients. We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter, randomized, double-blind placebo-controlled outcome study (ClinicalTrials.gov Identifier: NCT01115855). The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of <1 for the hazard ratio.Methods and Results:HFrEF patients with NYHA functional class II–IV and an EF ≤35% received eplerenone (n=111) or placebo (n=110) on top of standard therapy for at least 12 months. The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF. The primary endpoint occurred in 29.7% of patients in the eplerenone group vs. 32.7% in the placebo group [hazard ratio=0.85 (95% CI: 0.53–1.36)]. Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone. A total of 17 patients (15.3%) in the eplerenone group and 10 patients (9.1%) in the placebo group died. Adverse events, including hyperkalemia, were similar between the groups.Conclusions:Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study.
著者
Kyoko FUKUMOTO Takashi KOBAYASHI Kazuo KOMAMURA Shiro KAMAKURA Masafumi KITAKAZE Kazuyuki UENO
出版者
日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長
雑誌
Drug Metabolism and Pharmacokinetics (ISSN:13474367)
巻号頁・発行日
vol.20, no.6, pp.423-427, 2005 (Released:2006-01-11)
参考文献数
30
被引用文献数
13 11

We investigated whether there was a stereoselective effect of amiodarone on the pharmacokinetics of carvedilol. Among a series of 106 inpatients with heart failure, 52 received carvedilol monotherapy (carvedilol group) and 54 received carvedilol plus amiodarone (carvedilol+amiodarone group). The serum carvedilol concentration administered/dose ratio was compared between the two groups based on HPLC measurement of the serum levels of carvedilol, amiodarone, and desethylamiodarone. In 6 patients from the carvedilol group, serum carvedilol levels were compared before and after coadministration of amiodarone. There was no significant between-group difference of the serum concentration to dose (C/D ratio) for the R-enantiomer carvedilol, however, the C/D ratio for the S-enantiomer and the serum S-carvedilol to R-carvedilol (S/R) ratio were both significantly lower in the carvedilol group than in the carvedilol+amiodarone group(47.8±56.7 versus 95.3±105 ng/mg/kg, P=0.0048 and 0.460±0.207 versus 0.879±0.377 ng/mg/kg, P<0.001), respectively. Furthermore, the mean S-carvedilol concentration over 14 days of coadministration with amiodarone was higher than that before coadministration (6.54±1.73 ng/mL versus 3.03±0.670 ng/mL, P<0.001). These results suggest that metabolism of S-carvedilol was markedly inhibited by coadministration of amiodarone.
著者
Noboru Oda Tomoko S. Kato Akihisa Hanatani Kazuo Niwaya Takeshi Nakatani Hatsue Ishibashi-Ueda Soichiro Kitamura Kazuhiko Hashimura Masafumi Kitakaze Kazuo Komamura
出版者
The Japanese Society of Internal Medicine
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
vol.49, no.11, pp.1013-1016, 2010 (Released:2010-06-01)
参考文献数
15
被引用文献数
7 10

Reversible posterior leukoencephalopathy syndrome (RPLS) is one of the important adverse events following organ transplantation, associated with calcineurin inhibitors (CNIs). We describe a case of 54-year-old woman, who was diagnosed with RPLS within weeks after transplantation. Considering the risk of causing fatal rejection by discontinuation of CNIs, the immunosuppressive regimen of the patient was switched from a cyclosporine A-based regimen to a tacrolimus-based regimen. The patient recovered rapidly from RPLS following the switch to tacrolimus. This case demonstrated that not only discontinuation but also a substitution of CNIs would be a valid treatment option for RPLS in transplant recipients.
著者
Mahoto Kato Kazuo Komamura Masafumi Kitakaze
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.70, no.12, pp.1658-1660, 2006 (Released:2006-11-25)
参考文献数
17
被引用文献数
6 15

A 77-year-old man was referred to hospital because of dyspnea on exertion. Although the patient had been fully medicated for chronic heart failure (CHF) caused by hypertensive heart disease, the echo-estimated left ventricular end-diastolic pressure (LVEDP) and brain natriuretic peptide (BNP) level had continued to be high for at least 2 years. Pulmonary functional examination revealed concomitant chronic obstructive pulmonary disease (COPD). Because β-agonists were expected to exacerbate the CHF, inhalation of tiotropium, a non-β-adrenergic bronchodilator and novel M3 muscarinic receptor antagonist, was used to treat the COPD. Not only did the pulmonary function improved but the treatment also safely ameliorated CHF signs including LVEDP and plasma BNP. (Circ J 2006; 70: 1658 - 1660)
著者
Ryozo Nagai Koichiro Kinugawa Hiroshi Inoue Hirotsugu Atarashi Yoshihiko Seino Takeshi Yamashita Wataru Shimizu Takeshi Aiba Masafumi Kitakaze Atsuhiro Sakamoto Takanori Ikeda Yasushi Imai Takashi Daimon Katsuhiro Fujino Tetsuji Nagano Tatsuaki Okamura Masatsugu Hori the J-Land Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.77, no.4, pp.908-916, 2013 (Released:2013-03-25)
参考文献数
24
被引用文献数
21 90

Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25–50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1–10μg·kg–1·min–1 according to the patient’s condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.  (Circ J 2013; 77: 908–916)
著者
Ryozo Nagai Koichiro Kinugawa Hiroshi Inoue Hirotsugu Atarashi Yoshihiko Seino Takeshi Yamashita Wataru Shimizu Takeshi Aiba Masafumi Kitakaze Atsuhiro Sakamoto Takanori Ikeda Yasushi Imai Takashi Daimon Katsuhiro Fujino Tetsuji Nagano Tatsuaki Okamura Masatsugu Hori the J-Land Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-1618, (Released:2013-03-15)
参考文献数
24
被引用文献数
21 90

Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25–50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1–10μg·kg–1·min–1 according to the patient’s condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.