Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).

Feng XU; Yuan Bian; Guo Qiang Zhang; Lu Yao Gao; Yu Fa Liu; Tong Xiang Liu; Gang LI; Rui Xue Song; Li Jun SU; Yan Ju Zhou; Jia Yu Cui; Xian Liang Yan; Fang Ming Guo; Huan Yi Zhang; Qing Hui LI; Min Zhao; Li Kun MA; Bei An You; Ge Wang; Li Kong; Jian Liang MA; Xin Fu Zhou; Ze Long Chang; Zhen Yu Tang; Dan Yu YU; Kai Cheng; Li Xue; Xiao LI; Jiao Jiao Pang; Jia Li Wang; Hai Tao Zhang; Xue Zhong YU; Yu Guo Chen

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Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).

Author: Feng XU ¹ ; Yuan BIAN ² ; Guo Qiang ZHANG ³ ; Lu Yao GAO ¹ ; Yu Fa LIU ⁴ ; Tong Xiang LIU ⁵ ; Gang LI ³ ; Rui Xue SONG ¹ ; Li Jun SU ⁴ ; Yan Ju ZHOU ⁵ ; Jia Yu CUI ⁶ ; Xian Liang YAN ⁷ ; Fang Ming GUO ⁸ ; Huan Yi ZHANG ⁹ ; Qing Hui LI ¹⁰ ; Min ZHAO ¹¹ ; Li Kun MA ¹² ; Bei An YOU ¹³ ; Ge WANG ¹⁴ ; Li KONG ¹⁵ ; Jian Liang MA ¹⁵ ; Xin Fu ZHOU ¹⁶ ; Ze Long CHANG ¹ ; Zhen Yu TANG ¹ ; Dan Yu YU ¹ ; Kai CHENG ¹ ; Li XUE ¹ ; Xiao LI ¹ ; Jiao Jiao PANG ¹ ; Jia Li WANG ¹ ; Hai Tao ZHANG ¹⁷ ; Xue Zhong YU ¹⁸ ; Yu Guo CHEN ¹
Author Information

1. Department of Emergency Medicine, Qilu Hospital of Shandong University, Acute Heart Failure Unit (AHFU), Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Jinan 250012, China.
2. Department of Emergency Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
3. Department of Emergency, China-Japan Friendship Hospital, Beijing 100029, China.
4. Department of Emergency, Zibo Central Hospital, Zibo 255036, China.
5. Department of Emergency, Weifang People's Hospital, Weifang 261041, China.
6. Department of Cardiology, Binzhou People's Hospital, Binzhou 256600, China.
7. Emergency Medicine Department, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
8. Department of Cardiology, Yantaishan Hospital, Yantai 264003,China.
9. Department of Cardiology, the Central Hospital of Taian, Taian 271000, China.
10. Department of Cardiology, Shenli Oilfield Central Hospital, Dongying 257000, China.
11. Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China.
12. Department of Cardiology, the First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei 230001, China.
13. Department of Cardiology, Qilu Hospital of Shandong University (Qingdao), Qingdao 266031, China.
14. Department of Emergency Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao 266031, China.
15. Department of Emergency Center, Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Jinan 250011, China.
16. Department of Cardiology, Weihai Municipal Hospital, Weihai 264200, China.
17. Department of Surgical Intensive Care Unit, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China.
18. Department of Emergency, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
Publication Type:Journal Article
MeSH: Male; Female; Humans; Aged; Natriuretic Peptide, Brain; Simendan/therapeutic use*; Non-ST Elevated Myocardial Infarction; Heart Failure/drug therapy*; Peptide Fragments; Arrhythmias, Cardiac; Biomarkers; Prognosis
From: Chinese Journal of Internal Medicine 2023;62(4):374-383
CountryChina
Language:Chinese
Abstract: Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.