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

Abstract

OBJECTIVES: Recent trials demonstrated beneficial effects of beta-blockers in combination with standard heart failure medication. The mechanisms underlying this benefit are incompletely understood. We hypothesized that beta-blockers may augment the inhibition of the renin-angiotensin system in patients with left ventricular (LV) dysfunction treated with angiotensin-converting enzyme (ACE) inhibitors and/or diuretics by prevention of renin upregulation 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' prescriptions: antiplatelet agents alone (n=62) or in combination with ACE inhibitors, diuretics or beta-blockers (n=250). RESULTS: Plasma renin levels were elevated in patients taking ACE inhibitors or diuretics and ACE inhibitors plus diuretics (adjusted means from multiple 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 antiplatelets alone (16.1 mU L-1, 95% CI = 13.5-19.3, P < 0.05 each). The combinations of beta-blockers with ACE inhibitors or diuretics and beta-blockers with ACE inhibitors plus diuretics were related to markedly suppressed plasma renin levels (adjusted means 16.4 [13.1-20.6] and 32.1 [23.3-44.3]) as compared with respective patient groups without beta-blockers (P < 0.01 each). CONCLUSIONS: Concomitant beta-blocker treatment can prevent the reactive renin stimulation and potentially the escape from effective inhibition of the renin-angiotensin system in patients with LV dysfunction after MI treated with ACE-inhibitors and/or diuretics.