Valsartan in acute myocardial infarction trial (VALIANT): rationale and design.
BACKGROUND
Survivors of acute myocardial infarction (MI) complicated by heart failure and/or resulting in left ventricular dysfunction are at heightened risk for subsequent death and major nonfatal cardiovascular events. Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor has consistently been demonstrated to result in reductions in these risks by approximately 20%. The development of angiotensin II receptor blockers offers a new, more specific, and theoretically more complete pharmacologic mode to inhibit the adverse influence of angiotensin II.


METHODS
Valsartan in Acute Myocardial Infarction (VALIANT) is a multicenter, double-blind, randomized, active controlled parallel group study comparing the efficacy and safety of long-term treatment with valsartan, captopril, and their combination in high-risk patients after MI. The trial is designed with 3 arms, giving equal statistical consideration to survival comparisons of captopril versus the angiotensin II receptor blocker valsartan, as well as the combination of captopril plus valsartan, compared with a proven effective dose of captopril. This 14,500-patient trial is designed with an 86% power to detect a 15% reduction in mortality rate with either use of valsartan compared with captopril. The trial encourages optimal individualization of other proven therapies in acute and chronic infarction, and the international patient body ensures good representation of multiple practice patterns.


CONCLUSIONS
VALIANT is a large international investigative effort that will evaluate the role of valsartan in the management of patients with MI associated with heart failure and/or left ventricular dysfunction. The use of a proven dose of captopril and the comparator arms with valsartan alone or in combination with captopril provides a unique test of whether the angiotensin II receptor blocker can make an additional improvement in clinical outcomes beyond angiotensin-converting enzyme inhibitors.
Pfeffer
M A
MA
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. mpfeffer@rics.bwh.harvard.edu
McMurray
J
J
Leizorovicz
A
A
Maggioni
A P
AP
Rouleau
J L
JL
Van De Werf
F
F
Henis
M
M
Neuhart
E
E
Gallo
P
P
Edwards
S
S
Sellers
M A
MA
Velazquez
E
E
Califf
R
R
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D002423:Cause of Death; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D016017:Odds Ratio; D018579:Patient Selection; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D018401:Sample Size; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D002216:Captopril; D014633:Valine