| Objective: This trial was initiated to evaluate safety of recombinant human brain natriuretic peptide?rh-BNP? in elderly patients with acute heart failure?AHF?.Methods: This was a single blinded, placebo-controlled and randomized trial. From July 2014 to July 2015, all consecutive elderly patients with AHF in our cardiology department were enrolled. Eligible patients were randomly assigned to receiving rh-BNP?rh-BNP group, rh-BNP? or nitrates?control group, CON? by means of random number table. Inclusion criteria: AHF patients no less than 75 years old with previous cardiac function of NYHA III-IV, LVEF<45%. Exclusion criteria: patients with cardiogenic shock, intravascular volume depletion or any contraindication of vasodilators; patients with severe disease, such as hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, severe pulmonary hypertension, severe infection, severe renal dysfunction(eGFR<30 ml·min-1·1.73m-2). In rh-BNP group, on basis of basic anti-HF drug intervention and etiological treatment, rh-BNP was given with a loading dose of 1.5ug/kg, and then rh-BNP was pumped at a speed of 0.0075 ug/kg·min?loading dose would not be given if the patient's systolic blood pressure was less than 90 mm Hg? which could be adjusted according to blood pressure and clinical symptoms of the patients, and gradually increased from 0.0075-0.0250ug/kg·min for 72 hours, and then gradually reduced the dose to stop within 4 hours. In CON group, on basis of basic anti-HF drug intervention and etiological treatment, patients were given intravenous nitroglycern for 72 hours, and then gradually reduce the dose to stop within 4hours. Other medications including diuretics, angiotensin-converting enzyme inhibitors?ACEI? or Ang ? receptor antagonist?ARB?, vasodilators were all used in accordance with the current guidelines. Clinical improvements of symptoms and signs?including dyspnea, rale, edema, peripheral arterial blood oxygen saturation? were observed. Urine output was precisely recorded. Serum Creatinine?SCr? and Cystatin C?CysC? were measured premedication and at 24 h, 72 h, 1 week, 1 month and 6 months after medication, estimated glomerular filtration rate?eGFR? were calculated accordingly. Adverse events, such as malignant ventricular arrhythmia and cardiogenic death were observed. All the data were analyzed using SPSS 23.0, P<0.05?two-sided? was defined as statistically significant.Results: Of the 65 patients enrolled, 33 were randomly assigned to receive rh-BNP?rh-BNP group, 19 male, average age 78.12±3.50 years old? and 32 were randomly assigned to receive placebo?CON group, 17 male, average age 78.56±2.83 years old?. All patients participated the whole process. 1 Baseline characters There were no significant differences between the two groups in baseline characteristics, including mean age, gender distribution, body mass index?BMI?, risk factors, basic heart rate, systolic blood pressure, diastolic blood pressure, electrolytes, BNP, original disease classfication, oral drugs and so on? P>0.05?. 2 Clinical observations rh-BNP improved symptom and signs?including dyspnea, rale, edema, peripheral arterial blood oxygen saturation? more effectively than placebo. Urine output was more in the rh-BNP group than CON group the first and second day after treatment. There was no significant difference in urine output for the third day between the two groups. 3 Changes in renal function parameters 3.1 Changes in SCr There was no statistical difference in premedicational SCr between the two groups. There was a upward trend of SCr compared with baseline one day after treatment. There were no significant differences in SCr between the two groups and compared with baseline. On day 3, there was a significant difference compared with baseline in rh-BNP group?98.0±14.5 umol/L vs. 87.0±13.9 umol/L, P<0.05?, however the difference of the CON group was not significant. There was a significant difference between the two groups in SCr?98.0±14.5 umol/L vs. 91.1±13.9 umol/L,P<0.05?. SCr of the two groups dropped to baseline on day 7 after treatment. There were no significant difference in SCr between the two groups and compared with baseline. One month after treatment, there were no significant difference in SCr between the two groups and compared with baseline. Six months after treatment, there were no significant difference in SCr between the two groups and compared with baseline. 3.2 Changes in CysC There was no statistical difference in premedicational CysC between the two groups. There was a significant difference in CysC of the rh-BNP group compared with baseline one day after treatment?1.08±0.23 mg/L vs. 0.81±0.19 mg/L, P<0.05?. There was an upward trend of CysC in the CON group compared with baseline, with the difference not significant. There was a significant difference in CysC between the two groups?1.23±0.21 mg/L vs. 0.94±0.20 mg/L, P<0.05?. On day 3, there were significant differences compared with baseline of the two groups?rh-BNP: 98.0±14.5 umol/L vs. 87.0±13.9 umol/L, P<0.05, CON 0.94±0.20 mg/L vs. 0.77±0.20 mg/L, P<0.05?. There was a significant difference between the two groups in CysC?1.23±0.21 mg/L vs. 0.94±0.20 mg/L, P<0.05?. CysC of the two groups dropped to baseline on day 7 after treatment. There were no significant difference in CysC between the two groups and compared with baseline. One month after treatment, there were no significant difference in CysC between the two groups and compared with baseline. Six months after treatment, there were no significant difference in CysC between the two groups and compared with baseline. 3.3 Changes in eGFR There was no statistical difference in premedicational eGFR between the two groups. There was a downward trend of eGFR compared with baseline of the two groups one day after treatment. There were no significant differences in eGFR between the two groups and compared with baseline. On day 3, there was a significant difference compared with baseline in rh-BNP group(56.1±12.4 ml·min-1·1.73m-2 vs. 65.3±15.7 ml·min-1·1.73m-2, P<0.05), however the difference of the CON group was not significant. There was a significant difference between the two groups in eGFR(56.1±12.4 ml·min-1·1.73m-2 vs. 64.7±18.2 ml·min-1·1.73m-2,P<0.05). eGFR of the two groups returned to baseline on day 7 after treatment. There were no significant difference in SCr between the two groups and compared with baseline. One month after treatment, there were no significant difference in eGFR between the two groups and compared with baseline. Six months after treatment, there were no significant difference in eGFR between the two groups and compared with baseline. 4 Safety issues Malignant ventricular arrhythmias?MVA? case, cardic death, allergy, rash, nausea and vomitting occurred in neither groups.Conclusion: It is relatively safe to use rh-BNP in elder patients with acute heart failure. |
PDF Full Text Request