Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure

Beta blockers are known to suppress renin release in hypertension and in patients taking angiotensin-converting enzyme (ACE) inhibitors. This study sought to explore the effect of additional β blockade on neurohumoral modulation in patients with severe heart failure (HF) who received ACE inhibitors. Forty-nine patients with chronic HF who received ACE inhibitors were given metoprolol 50 mg or carvedilol 25 mg twice daily after a 4-week dose titration period in addition to standard therapy in a prospective trial. Samples of plasma renin activity (PRA), aldosterone, aminoterminal B-type natriuretic peptide (N-BNP), and atrial natriuretic peptide (ANP) were taken at baseline and at 4, 12, and 52 weeks after starting therapy. Treatment with either β blocker significantly lowered PRA at 4 weeks compared with baseline (−2.0 ± 0.6 nmol/L/hour, p = 0.006), but at 12 weeks, PRA had reduced to –1.1 ± 0.6 nmol/L/hour (p = 0.08), but at 52 weeks, it was not significantly different from baseline (+1.05 ± 0.6 nmol/L/hour, p = 0.13). Aldosterone levels did not change significantly from baseline at 4 or 12 weeks, although there was a nonsignificant trend for lower levels at 52 weeks (baseline 232 ± 154 pmol/L, 52 weeks 192 ± 100 pmol/L, p = 0.09). There was significant reduction in N-BNP and ANP together with an improvement in symptom and left ventricular systolic function at 1-year follow-up. These results indicate that the suppressive effect of β blockers on PRA in patients with HF taking ACE inhibitors is temporary, and that there is no significant effect on serum aldosterone levels.