Randomized Study Of The Effect Of Combining Candesartan With Fosinopril In Patients With Heart Failure

ForwardMultiple randomized, placebo controlled trials have demonstrated that angiote-nsin-converting-enzyme(ACE)inhibitors reduce the risk of death as well as the ri-skof major nonfatal cardiovascular events. Angiotensin-receptor blockers(ARB) of-feran alternative approach to the inhibition of the rennin-angiotensin system. Theidentification of a functioning chymase in humans that is capable of generating angiotensinâ…¡(A-â…¡) independently of ACE provide a rationale for inhibiting thedeleterious actions of angiotensinâ…¡at the AT₁ receptor more completely with an ARB. The discoveries of other angiotensin receptors with putatively favorableeffects on cardiovascular functi-on and structure support the hypothesis that angi-otensin-receptor blockers may offer c-linical benefits beyond those achieved withACEI. Alternatively, since the augment-ation of bradykinin levels may also con-tribute to the net therapeutid benefits of AC-EI, concurrent treatment with an A-CEI and an ARB might be the most effective strat-egy. Candesartan is a new kind of ARBs , we hope the efficacy of Candesartan plus Fosinopril is superior to Fosinopril alone to the CHF patients.Materials and MethodsSixty men and women, 18 years old or older, with a history and clinical finding of heart failure were eligible to participate in this study. Patients had heart failure of NYHA classⅡ～Ⅳand were clinically stable. They had to had documented left ventricular dysfunction with an ejection fraction of less than 40 percent. The exclusion criteria included pregnancy, acute myocardial infarct-tion, unstable angina, cardiac surgery or percutaneous transluminal angioplasty with in the past 3 months myocarditis bradycardia cerebral vascular accidents within the 3 months, clinical important renal, hepatis or hematological disorder (s-ome study has proved that impaired renal function is independently associated with heightened risk for death ,cardiovascular death, and hospitalized for heart failure in patients with CHF and both preserved as well as reduced LVEE), an-y terminal disease with a life expectancy of less than 1 year.This is a randomized and controlled study. Eligible patients were randomlyassigned in a 1:1 ratio. The two group have similar age sex primary diseases and other background medications(beta-blockers, Digoxin, diuretics et al). (P＞0.05) The patients who have been used the ACEIs or ARBs must stop to use them for at least 2weeks. They were assigned Candesartan(8mg/day) plus Fosinopril(10mg/day) and Fosinopril(10mg/day) alone and followed up for 8 weeks. Study visits took place at four week intervals and the doses were not changed. Baseline evaluations included recording case history, signs NYHA classes, blood c-hemistry.Staristical AnalysisValues are present as (?)±s. The data of our study were analyzed by SPSS12.0software. Sex, age, primary diseases, NYHA grade and other background medications were analyzed by x² test. Changes in LVEF, LVDd, LAD, potassi-um and creatinine following the therapy were tested by t-test.ResultsBase-line characteristics of the patients are similar. (P＞0.05) Comparing w-ith the baseline, the SBP and DBP decreased but did not decreased significantlytothe same degree in both groups. LVEF increased at 4 weeks and 8 weeks but the two groups are similar comparing with baseline at 4weeks. LVEF of the co-mbination therapy group did not decrease significantly at 8 weeks. LVDd of th-e mono-therapy group did not decrease significantly at 8 weeks. LVEDd of the two groups are similar at 4 weeks but the combination therapy group decreasedsignificantly at 8 weeks. LAD of the the combination therapy group decreased s-ignificantly at 8 weeks. The NYHA grade of the two groups are similar (P＞0.05). The influence to potassium and creatinine of the two groups are similar(P＞0.05). Each group had a patient hospitalization for heart failure.DiscussionWe found that the combination of Candesartan and Fosinopril therapy for 8 weeksat doses which are standard in China improved the LVEF, LVEDd, LAD Adding Candesartan to standard heart failure treatment, often including an AC-E inhibitor, aβ-blocker, or an aldosterone antagonist (or all 3) in CHF pati-nts with LVEF≤40ï¼…can still obtain benefits. In conclution, this approach off-ers us an opportunity to make additional improvements in the poor prognosis of CHF patients when left ventricular systolic dysfunction is present by adding thisARB to other treatments that are proven to be efficacious in similar settings. T-olerability and safety are good.ConelutionThis approach offers us an opportunity to make additional improvements in the poor prognosis of CHF patients when left ventricular systolic dysfunction is p-resent by adding this ARB to other treatments that are proven to be efficacious i-n similar settings. Tolerability and safety are good.