Marked suppression of renin levels by beta-receptor blocker in patients treated with standard heart failure therapy: a potential mechanism of benefitfrom beta-blockade

Objectives. Recent trials demonstrated beneficial effects of beta -blockers in combination with standard heart failure medication. The mechanisms unde rlying this benefit are incompletely understood. We hypothesized that beta -blockers may augment the inhibition or the renin-angiotensin system in pat ients with left ventricular (LV) dysfunction treated with angiotensin-conve rting enzyme (ACE) inhibitors and/or diuretics by prevention of renin upreg ulation that occurs in such patients. Design. We examined plasma renin levels (direct radioimmunometric assay) in 312 men with previous myocardial infarction (MI) and echocardiographic LV dysfunction. Patients took medication according to their physicians' prescr iptions: antiplatelet agents alone (n = 62) or in combination with ACE inhi bitors, diuretics or beta -blockers. Results. Plasma renin levels were elevated in patients taking ACE inhibitor s or diuretics and ACE inhibitors plus diuretics (adjusted means from multi ple regression analysis were 28.5 mU L-1 [95% CI = 20.6-39.5] and 73.7 mU L -1 [95% CI = 49.9-109.9], respectively) compared with patients on antiplate lets alone (16.1 mU L-1. 95%, CI = 13.5-19.3, P < 0.05 each). The combinati ons of <beta>-blockers with ACE inhibitors or diuretics and beta -blockers with ACE inhibitors plus diuretics were related to markedly suppressed plas ma renin levels (adjusted means 16.4 [13.1-20.6] and 32.1 [23.3-44.3]) as c ompared with respective patient groups without beta -blockers (P < 0.01 eac h). Conclusions. Concomitant <beta>-blocker treatment can prevent the reactive renin stimulation and potentially the escape from effective inhibition of t he renin-angiotensin system in patients with LV dysfunction after MI treate d with ACE-inhibitors and/or diuretics.