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.
OBJECTIVE
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.


METHODS
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.
Holmer
S R
SR
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany. stephan.holmer@klinik.uni-regensburg.de
Hengstenberg
C
C
Mayer
B
B
Engel
S
S
Löwel
H
H
Riegger
G A
GA
Schunkert
H
H
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012083:Renin / Q000097:blood*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D012083:Renin