Candesartan Prevents Myocardial Fibrosis during Progression of Congestive Heart Failure

BACKGROUND: The goal of this study was to determine whether an Angiotensin II receptor antagonist, candesartan, prevents myocardial fibrosis more effectively than enalapril in animals with a non-ACE pathway during the progression of congestive heart failure (CHF). METHODS AND RESULTS: Dogs were randomly assigned to one of four groups: (1) rapid ventricular pacing (240 bpm); (2) concomitant candesartan cilexetil (1.5 mg/kg/d) and rapid pacing; (3) concomitant enalapril (1.9 mg/kg/d) and rapid pacing; (4) sham-operated control. The expression of collagen type I & III mRNA and the collagen volume fraction, which were significantly increased in the pacing-only group, were suppressed by both treatments; it was lower in the candesartan than the enalapril group. Although there were no differences in the LV stiffness coefficient (beta) among all pacing groups, the absolute changes in beta from the control values were smaller in the candesartan group, but not the enalapril group, compared with the rapid-pacing-only group. CONCLUSIONS: The present study demonstrates that in animals with a non-ACE pathway, candesartan suppressed myocardial fibrosis during the progression of CHF in comparison with enalapril. Furthermore, candesartan prevented an increase in LV stiffness. These findings imply potential clinical applications for candesartan in the management of CHF to prevent myocardial fibrosis. Further prospective evaluation and clinical study will be necessary before deciding on the net benefits of candesartan in comparison to enalapril.