A Clinical Comparative Study Between RhBNP And Urapidil Hydrochloride In ACS Patients With AHF

Objective: To compare therapeutic efficiency and safety betweenintravenous pumping recombinant human brain natriuretic peptide (rhBNP)and Urapidil Hydrochloride in treatment of patients with ACS combined withAHF.Methods:1Subjects: Having excluded shock and severe hypotension, atotal of62patients (40males and22females, aging from49to82, average67.84±9.45years old)with acute coronary syndrome(ACS) combined withacute heart failure(AHF) of the fifth department of cardiology in the secondhospital of Hebei medical university from January2012to January2013wereenrolled into this study.1.1Criteria of inclusion:①Compliance with diagnosis of acute coronary syndrome;②Compliance with cardiac functional grading of NYHA III-Ⅳ orKillip Ⅱ~Ⅲ.1.2Criteria of exclusion:①Shock (systolic pressure was <80mmHg; pulse pressure differencewas <20mmHg; slender pulse was at a speed higher than100beats/min orcouldn’t be touched; clammy limbs, positive reaction to compression onsternal skin, pale mucosa or cyanosis, urine volume was fewer than30ml/h oranuresis; drop of systolic pressure from the original level was more than30%in patients with original hypertension; abnormal consciousness.②Valvular heart disease, restricted or hypertrophic cardiomyopathy,acute myocarditis.③Contraindications to anticoagulation: There was a history of irregularbleeding or hemorrhagic apoplexy recently, operation or severe injury within6weeks, cardiopulmonary resuscitation stroke (chest compression was more than10minutes or treated with tracheal intubation, etc.), gastrointestinalbleeding within6months, and infective endocarditis.④Allergic constitution.⑤Need for mechanical ventilation.⑥Severe dysfunction of liver and kidney, such as, transaminase washigher than2times of the upper limit of normal, serum creatinine was>2.5mg/dl.⑦Existence of autoimmune disease, severe injury, hemorrhagic diseases,and tumor.⑧Patients or family members refused to participate in this study.2Division and interventions:2.1According to the digital random table, patients were divided into2groups randomly which were Group rhBNP (32cases) and Group urapidil (30cases).2.2Group rhBNP were given rhBNP slowly with the loading dose of1.5μ g/kg by intravenous injection within2-5minutes, and then rhBNP waspumped at a beginning speed of0.0075μg/kg·min. In the case of ensuringeffective circulating blood volume, the dose was increased0.0075-0.030μg/kg.min according to patient’s symptoms until the maximum tolerated dosewithin6h with which rhBNP was continuously intravenous pumped for72hours,then reduced and stopped gradually within24hours.2.3Guaranteeing BP at the same range, urapidil was continuouslypumped in Group Urapidil with an initial dose of0.5μg/kg.min and increasedit until the maximum tolerated dose(<the maximum dose12.0μg/kg.min)within6h with which Urapidil was maintained for72hours,then induced andstopped gradually within24hours.2.4Basic treatments: Deslanoside and furosemide could be used in twogroups according to patient’s dyspnea and heart rate. Each group of patientsreceived the same regular treatment of oxygen inhaling, anticoagulation,antiplatelet aggregation, lipid regulation, angiotensin converting enzymeinhibitor/angiotensin receptor blocker(ACEI/ARB), beta blockers, and ECG monitoring. If the urine volume increased significantly, the patients would begiven supplement of potassium and sodium.3Indexes observed and statistic treatment: We compared the efficiency ofintravenous pumped urapidil and rhBNP in treatment of acute coronarysyndrome combined with acute heart failure through some indexes before andafter treatment in two groups, such as degree of dyspnea, respiratory rate,arterial partial pressure of oxygen, blood pressure, heart rate, urine volume in24hours, difference of input and output in24hours, value of NT-proBNP, leftventricular ejection fraction (LVEF), left ventricular end diastolic volume(LVEDV), left ventricular end-systolic volume(LVESV), walking distancewithin6minutes and results of coronary angiography. Two medications’ safetywere evaluated by comparing incidences of adverse reactions and majoradverse cardiac events (MACE), such as hypotension, electrolyte disturbance(such as hyponatremia, hypokalemia), kidney injury (serum creatinine,clearance rate of endogenous creatinine). Statistic data were analyzed byPASW19.0, it was considered statistical significance when P <0.05.Results:1The sex, age, weight, smoking, drinking, diabetes prevalence,hypertension prevalence, hyperlipidemia prevalence, degree of dyspnea onadmission, oxygen partial pressure of arterial blood, breathing rate, NYHA orKillip classification,blood pressure, heart rate, cardiac function,6minuteswalking distance, serum creatinine level and endogenous creatinine clearance,serum sodium and potassium, NT-proBNP, LVEF, LVEDV, LVESV and usingother drugs in the two group patients had no significant difference (P>0.05).2Dyspnea was improved more significantly after treatment in bothgroups than that of baseline (P <0.05), which in the rhBNP group was moresignificant than that in the urapidil group (P <0.05); Breathing rate sloweddown more significantly than that before treatment (P <0.01), which in therhBNP group was more significant than that in the urapidil group (P <0.05);Oxygen partial pressure of arterial blood increased more significantly than thatbefore treatment (P <0.05), which in the rhBNP group was more significantthan that in the urapidil group (P <0.05); Killip classification improved more significantly than that before treatment (P <0.01), which in the rhBNPimproved more obviously than that in urapidil group; Blood pressuredecreased more significantly than that before treatment (P <0.05), which inthe urapidil group was more significant than that in the rhBNP group (P <0.05); Heart rate declined more obviously in48h after the treatment (P <0.01),then became stable, which in the rhBNP group was more significant than thatin the urapidil group (P <0.05); The quantity difference between in and out in24hours and urine volume in24hours increased more significantly in both thetwo groups (P <0.01), which in the rhBNP group was more significant thanthat in the urapidil group (P <0.05);3The value of NT–proBNP became lower significantly than beforetreatment in both the two groups (P <0.05), and which in the rhBNP groupreduced more significantly than that in the urapidil group (P=0.036).4The change of the blood sodium and potassium in two groups after thetreatment was not significant (P>0.05). But the blood creatinine levelsbecame lower significantly than that before the treatment (P <0.05), which at72h after treatment lower obviously than that at24h after treatment in therhBNP group (97.3±14.1umol/l VS108.3±26.6umol/l P=0.043). But in theurapidil group, the serum creatinine level of48h,72h after treatment had noobvious change than that of24h after treatment (P>0.05). In both the twogroups, the endogenous creatinine clearance rate became higher significantlythan before treatment (P <0.05).In the rhBNP group, the endogenouscreatinine clearance rate at72h after treatment became higher obviously thanthat at24h after treatment (75.16±10.59ml/min VS68.95±11.27ml/min P=0.027). But in the urapidil group, the endogenous creatinine clearance rate of48h,72h after treatment had no obvious change than that of24h aftertreatment (P>0.05).5The patients of the two groups were performed coronary angiographyexamination, the result was:6cases both in rhBNP group and in urapidilgroup were single branch lesion;9cases in rhBNP group were doublebranches lesions (stenosis>75%), while12cases in urapidil group;17cases in rhBNP group were three branches lesions, while12cases in urapidil group.According to the SYNTAX score system, the coronary lesion of the rhBNPgroup was more serious than that in the urapidil group (37.2±8.82VS32.3±7.42, P <0.05).66minutes walking distance of the two group patients in1week,1month after treatment were significantly increased than that before treatment(P <0.05), in the rhBNP group increased more significantly than that in theurapidil group(P <0.01).7The change of LVEF of both the two groups in1week after treatmentwere not more significant than that before treatment (35.5±5.27%VS34.5±4.56%，35.7±4.32%VS35.9±4.77%，P>0.05).But in1month aftertreatment,the change of LVEF of both the two groups were more significantthan that before treatment (40.7±5.45%VS34.5±4.56%，38.2±3.91%VS35.7±4.32%，P <0.05), which in the rhBNP group was more significant thanthat in the urapidil group (P=0.043). LVEDV and LVESV of both the twogroups all minished more significantly than that before treatment (P>0.05).In1month after treatment, LVEDV and LVESV of the rhBNP groupminished more significantly than that of the urapidil group(P <0.05).8Adverse reactions in the two groups: allergic reaction was not found inboth the two groups.1case in rhBNP group happened hypotension while7cases in urapidil group, but they were not appeared again after adjustingdosage. Compared with the urapidil group, the incidence of hypotension waslower in rhBNP group, which was both statistical significance (P <0.05).1case of hyponatremia appeared in rhBNP group during treatment (Na127mmol/l, urine volume3300ml/d), and1in urapidil group (Na129mmol/l,urine volume2900ml/d)24hours after treatment, it did not appear again aftergiving high salt liquid and salty diet.1case of hypokalemia appeared in bothrhBNP group and urapidil group during treatment (K3.0mmol/l, urine volume3000ml/d,K3.2mmol/l, urine volume2800ml/d respectively)24hours aftertreatment, it did not happen again after giving potassium supplement and oralpotassium supplement. Each of two groups has3cases of ventricular arrhythmia (ventricular premature beat, short ventricular tachycardia).2casesof photism or phonism of mental symptom appeared in urapidil group,none inrhBNP group, but they were not appeared again after adjusting dosage. In thecase of maintaining the systolic blood pressure in130-90mmHg and diastolicblood pressure in80-60mmHg, there was no renal insufficiency occurred orthe original renal insufficiency aggravated in the two groups.9Within1months of the study, incidence of MACE (MACE including inheart failure became obviously worse (Killip classification increased1grade orhigher), deteriorated again after drug withdrawal, severe ventriculararrhythmias and death) in two groups:1case of malignant arrhythmia inrhBNP group;1case improved deteriorated again after drug withdrawal, and1case of malignant arrhythmia in urapidil hydrochloride group. There was nodeath case in both the two groups, comparison between the two groups,therewas no statistical difference (P>0.05).10Continuously intravenous pumping rhBNP maximum tolerated dose ofthe rhBNP group was0.0197±0.0076μ g/kg.min, and urapidil hydrochloridemaximum tolerated dose of the urapidil group was5.3±0.46μ g/kg.min.Conclusions:1RhBNP might be more effectively improve the hemodynamic disorderand left ventricular systolic function than that of Urapidil Hydrochloride inpatients with acute coronary syndrome combined with acute heart failure.2Under effective circulative blood volume and using conventionaldosage of rhBNP and Urapidil Hydrochloride, there was no renal damage.