A Clinical Comparied Study Of Different Dosages Of Valsartan In Patients With Chronic Heart Failure

Objective:The purpose of study was to evaluate the efficacy of large dosage(320mg) valsartan versus small dosage(80mg) valsartan in patients with CHF by comparing the level of BNP and cardiac remodeling index at 6th month ,3th month, 6th month,as well analyzing correlation between the two indexes.Methods:From June 2005 to December 2005,a total of 60 in-hospital patients(48 males,12 females) with CHF according to diagnostic criteria of WHO were randomly assigned to receive small dosage Valsartan (A group)and large dosage Valsartan(B group) in addition to standard therapy for a total six months. Inclusion criteria: Men and women 18 years old or older with a history and clinical findings of heart failure for at least three months before screening ; Patients had heart failure of New York Heart Association (NYHA) class II, III, or IV and were clinically stable; In addition, they had to have documented left ventricular dysfunction with an ejection fraction of less than 45 percent and left ventricular dilatation with an echocardiographically measured short-axis internal dimension at end diastole greater than 2.9 cm per square meter of body-surface area ; no hypersensitive response for ACEI. Exclusion criteria: pregnancy; lactation woman or not taking contraception, possible pregnancy woman; postpartum cardiomyopathy; cor pulmonale; aggravating heart failure; acute myocardial infarction, cardiac operation, PCI in three months; severe valvular heart failure ; hypertrophic cardiomyophty (HCM); patients had persistent ventricular tachycardia in past three months with syncope, but not receiving treatment; in the past or in the future taking heart transplantation; cerebral hemorrhage in three months; severe renal disease (Crea>3.0mg/dl), liver disease , hematologic disease; baseline of potassium>5.5mmol/Lg,baseline of SBP<90mmHg.After assignment the group A was treated with Valsartan 80mg once daily ,in addition to the traditional treatment(ACEI 25mg tid,, hydrochlorothiazide 25mg qd, digitalis 0.125mg qd). In the B group Valsartan was initiated at a dose of 80 mg once daily, and the dose was doubled every one week, if no hypotension , renal inadequacy, hyperkaliemia ,until a target dose of 160 mg twice daily was reached, in addition to the traditional treatment .Before treatment and 1 month,3 months, 6 months after treatment, plasma level of BNP was measured by the fast BNP instrumentation (Biosite Triage ,USA) with the bed nearby. In the same time segment ,Doppler echocardiography was performed to measured functional parameter of left ventricular such as Left ventricular end systolic diameter,(LVESD),Left ventricle end diastolic diameter (LVEDD), Interventricular septal diameter(IVSD),left ventricle post wall diameter(LVPWD),Left ventricle mass index(LVMI).Before treatment and follow-up ,all the patients measured blood pressure and heart rate every day ,taking the average value of six times.At the point of the sixth month,taking evaluation of treatment effectiveness(based on the NYHA).All data analyzed with SPSS12.0 statistic software, statistical significance was determined by P Value <0.05.Results: sixty patients were enrolled in this study(48 males,12 females, mean age 58.6±3.7 years).There were no significant differences between the two groups in the clinical characteristic, such as age , gender, risk factors (include smoking, essential hypertension, hyperlipidemia, diabetic mellitus) and primary cause of chronic heart failure, NYHA class. There were no statistical differences in plasma level of BNP and echocardiography index(LVEF,LVEDV,LVEDD,IVSD,LVPWD,LVMI). After receiving treatment of six months ,clinical efficacy rate(based on NYHA Class) indicated: in group A ,significant effective 10(37%),effective 12(44%),invalid 5(19%), total effective rate 81%;while in group B effective 23(70%), effective 9(37%),invalid 1(3%),total effective rate 97%;group B was significant better than group A, it showed the significant differences (χ2=3.958,P<0.05).In the first month after treatment ,there were not significant differences in BNP and echocardiography index contrast to those before treatment in the two group. At the point of the third month after treatment, there were improvement to some extent (including LVEF, LVEDV, LVEDD, IVSD, LVPWD, LVMI and plasma level of BNP) compared with baseline. Moreover in group B , these indexes (except LVEDV) were significant better than group A, it showed the significant differences (P <0.05,respectively).Though LVEDV of group B reduced more than one of group A, it showed not statistical differences between the two groups(183.38±31.65vs191.02±31.32 ,P=0.35), at the point of the sixth months after treatment, all the indexes(includingLVEF,LVEDV,LVEDD,IVSD,LVPWD,LVMI and plasma level of BNP) improved further, it showed statistic differences between the two groups. At the point of the first month ,SBP decreased significantly and showed statistic differences comparison with group A(120.43±11.58vs142.14±12.10,P<0.05).Changes of heart rate is the same as SBP, it showed significant differences(87.13±10.96vs105.35±10.53,P<0.001).In the following days, SBP and heart rate in group B decreased slowly and still showed significant differences comparison with Group A. In this study plasma level of BNP was a significant positive correlation with LVMI(r=0.642, P<0.01), while significant negative correlation with LVEF.(r=-0.502,P<0.01).In this sudy,there were four patient to appear hypotension(SBP<90mmHg).After reduced the dosage of diuretic,symptom of hypotension disappeared.At the end of investigation , no statistic difference in adverse events was found between the two group.Conclusions: in this study, compared with 80mg valsartan, 320mg valsartan is improved more effective in the treatment of CHF and can better delay the ventricle remodeling , having the same tolerance. Furthermore , level of BNP is a significant positive correlation with LVMI ,while significant negative correlation with LVEF.