Tetsuo Minamino1, Shuichiro Higo2, Ryo Araki2, Shungo Hikoso2, Daisaku Nakatani2, Hiroshi Suzuki3, Takahisa Yamada4, Masaaki Okutsu5, Kouji Yamamoto6, Yasushi Fujio7, Yoshio Ishida8, Takuya Ozawa9, Kiminori Kato10, Ken Toba11, Yoshifusa Aizawa12, Issei Komuro13. 1. Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University. 2. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. 3. Department of Cardiology, Showa University Fujigaoka Hospital. 4. Division of Cardiology, Osaka General Medical Center. 5. Department of Internal Medicine, Kawasaki Medical School General Medical Center. 6. Department of Medical Statistics, Osaka City University Graduate School of Medicine. 7. Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University. 8. Department of Internal Medicine, Kaizuka City Hospital. 9. Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences. 10. Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Niigata University Graduate School of Medical and Dental Sciences. 11. Department of Hematology, Tachikawa Medical Center. 12. Department of Research and Development, Tachikawa Medical Center. 13. Department of Cardiovascular Medicine, Tokyo University Graduate School of Medicine.
Abstract
BACKGROUND:Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results: We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).
RCT Entities:
BACKGROUND:Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results: We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).
Entities:
Keywords:
Acute myocardial infarction; Erythropoietin; Left ventricular ejection fraction