Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial.
OBJECTIVE
Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo.


RESULTS
AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function <or=40% but with an increased level of NP 3-10 days after admission to aliskiren, valsartan, their combination, and placebo. The primary endpoint was the change in NT-proBNP from baseline to Week 8. NT-proBNP declined significantly in each treatment arm, including placebo, by Week 8, though there were no differences in the reduction between treatment strategies (42% in placebo, 44% in aliskiren, 39% in valsartan, and 36% in combination arm). Although several subgroups had higher baseline levels of NP and greater reductions over the study period, there were no differences among treatment groups in any subgroup. There were no differences in clinical outcomes but there were more adverse events, including serious events and adverse events leading to early study drug discontinuation, in patients treated with active therapy.


CONCLUSIONS
In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS, there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan, aliskiren, or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy. Moreover, adverse events were reported more frequently in patients assigned to active therapy.
Scirica
Benjamin M
BM
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. bscirica@partners.org
Morrow
David A
DA
Bode
Christoph
C
Ruzyllo
Witold
W
Ruda
Mikhail
M
Oude Ophuis
Anthonius J M
AJ
Lopez-Sendon
Jose
J
Swedberg
Karl
K
Ogorek
Michal
M
Rifai
Nader
N
Lukashevich
Valentina
V
Maboudian
Mojdeh
M
Cannon
Christopher P
CP
McCabe
Carolyn H
CH
Braunwald
Eugene
E
D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan; D000092502:Renin Inhibitors
D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D005650:Fumarates; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C109794:pro-brain natriuretic peptide (1-76); C446481:aliskiren