Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure.
BACKGROUND
Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure.


RESULTS
Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration >100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and beta-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients' mean age was 68 years, mean ejection fraction was 31%, and mean+/-SD systolic blood pressure was 129+/-17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762+/-6123 pg/mL with placebo and fell by 244+/-2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo.


CONCLUSIONS
Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and beta-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated.
McMurray
John J V
JJ
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom. j.mcmurray@bio.gla.ac.uk
Pitt
Bertram
B
Latini
Roberto
R
Maggioni
Aldo P
AP
Solomon
Scott D
SD
Keefe
Deborah L
DL
Ford
Jessica
J
Verma
Anil
A
Lewsey
Jim
J
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D000577:Amides / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D020097:Natriuretic Peptide, Brain; C446481:aliskiren