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) / 中华内科杂志

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.

Effect of artificial cold exposure on the blood pressure of rats with carotid atherosclerosis / 中华神经医学杂志

Objective To study the effect of artificial cold exposure (ACE) on the level of blood pressure in carotid atherosclerotic rats, and the prophylactic effect of nimodipine on it. Methods One hundred and thirty SD rats were randomly divided into normal group (n=10), sham-operated group (n=10), and carotid atherosclerotic (CAS) group (n=110). High-fat diet was given to the sham-operated group and CAS group; normal diet was given to the control group. Then, 105 alive rats in the CAS group were further sub-divided into non-ACE group (n=40), ACE group (n=38) and nimodipine treatment group (n=37). All the groups were subjected to ACE for 3 d except non-ACE group, and kept at 22 °C throughout the experiment. During the ACE, an intragastric administration of nimodipine was given to the nimodipine treatment group. The changes of the blood pressure before and after ACE were analyzed and compared. Results The level of pre-ACE blood pressure in the sham-operated group and CAS group was significantly higher than that in the normal group (P＜0.05). The level of post-ACE blood pressure was significantly increased in the normal group, sham-operated group and ACE group, and significantly decreased in the nimodipine treatment group as compared with the level of pre-ACE one in these groups (P＜0.05). No significant differences were noted between the levels of pre-ACE and post-ACE blood pressure in the normal group, sham-operated group and ACE group (P＞0.05). The level of post-ACE blood pressure in rats treated with nimodipine was obviously decreased as compared with that in the ACE group (P＜0.05). Conclusion ACE could increase the level of blood pressure in carotid atherosclerotic rats and this effect might be lessoned by the administration of nimodipine.