title: Long-term combined therapy with an angiotensin type I receptor blocker and an angiotensin converting enzyme inhibitor prolongs survival in dilated cardiomyopathy.
abstract: The efficacy of ACE inhibitors (ACEIs) in the treatment of chronic heart failures is well documented. However, ACEIs may provide incomplete blockade of the renin-angiotensin system (RAS) because of the alternative pathways for angiotensin II (All) production. We hypothesized that more complete blockade of RAS by adding an AT1 receptor blocker (ARB) may have greater potential to decrease mortality associated with heart failure and improve cardiac function than monotherapy with ACEIs. The objective of this study was to evaluate the effect of combined therapy on cardiac functions and survival in cardiomyopathic hamsters. Male cardiomyopathic hamsters (BIO TO2) were administered either placebo (group C), enalapril (30 mg/kg/day) (group E), or enalapril (30 mg/kg/day) + valsartan (500 mg/ kg/day) (group EV), starting at the age of 6 weeks. Kaplan-Meier analysis was performed to assess the differences in survival. Cardiac functions were evaluated by echocardiogram and cardiac catheterization. Group EV showed significant increases in fractional shortening, LV dP/dTmax, and deceleration time, and showed significant decreases in left ventricular diastolic dimension, LV dP/dTmin, and early diastolic mitral velocity/atrial systolic velocity. Treatment with enalapril resulted in longer survival compared with placebo. Moreover, life expectancy (median probability of survival: 433 days) increased significantly in group EV compared with group E (P<0.05) as well as group C (P<0.001). It is concluded that combined therapy improved cardiac function and survival compared to placebo or enalapril monotherapy.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Chiba
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Hisao
authors.initials: H
authors.lastname: Onozuka
authors.forename: Taisei
authors.initials: T
authors.lastname: Mikami
authors.forename: Hideki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002452:Cell Count; D002908:Chronic Disease; D006224:Cricetinae; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000008:administration & dosage; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D011897:Random Allocation; D011945:Receptors, Angiotensin / Q000008:administration & dosage; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D004656:Enalapril; D000803:Angiotensin I