Comparison of high- versus low-tissue affinity ACE-inhibitor treatment on circulating aldosterone levels in patients with chronic heart failure

. Previous animal studies of chronic heart failure (CHF) suggest that angiotensin-converting enzyme (ACE) inhibitors of differing tissue avidity provide varying levels of renin-angiotensin system (RAS) suppression. Human studies have not consistently confirmed these animal findings. We hypothesised that production of circulating aldosterone (ALDO) would be suppressed to a greater extent in subjects treated with an ACE-inhibitor of higher tissue avidity. We randomised subjects with stable CHF to receive the low-tissue affinity ACE-inhibitor enalapril (ENAL) or the high-tissue affinity ACE-inhibitor trandolapril (TRAN), and assessed circulating ALDO levels at baseline and after eight weeks of treatment. Methods. Thirty clinically stable subjects with CHF and left ventricular ejection fraction (LVEF ) < 40% who were in a steady-state fluid balance were enrolled into a prospective, randomised double-blind trial. After a one month run-in period for standardisation to initial ACE-inhibition with ENAL, baseline circulating ALDO levels were measured and patients were randomised to receive ENAL 40 mg versus O TRAN 4 mg (or the maximally tolerated doses) for eight weeks. Final determination of ALDO levels were made at the end of the 8-week study period. Results. Baseline clinical characteristics including age, diabetes, LVEF, serum sodium, potassium and creatinine concentrations, and background medications were similar in both groups. We found no statistically significant difference in circulating ALDO levels between the ENAL and TRAN groups at the end of the 8-week study period. [ENAL (12.6 vs. 13.3 ng/dL);TRAN (12.5 vs. 14.5 ng/dL);p=NS]. Conclusion. We found no statistically significant difference in circulating ALDO levels between high- and low-tissue affinity ACE-inhibitor therapy. Further studies assessing ALDO production at the tissue level is warranted.