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(Circulation. 2001;104:e9039.)
© 2001 American Heart Association, Inc.

Report from the 94th Cardiovascular and Renal Drugs Advisory Committee Meeting, October 11, 2001

Thomas Fleming, PhD; Jeffrey Borer, MD; Raymond Lipicky, PhD; Paul W. Armstrong, MD

Department of BiostatisticsUniversity of Washington, Seattle, Washington
Division of PathophysiologyWeill Medical College at Cornell Universit, New York, NY
DirectorDivision of Cardiorenal Drug Products, Food and Drug Administration Rockville, Maryland
Division of CardiologyUniversity of Alberta, Edmonton, Alberta, Canada

An orally active, competitive, angiotensin-II antagonist (at the level of the angiotensin II type 1 receptor), valsartan (Diovan), was first developed and approved by the US Food and Drug Administration 5 years ago for the treatment of hypertension alone or in combination with other antihypertensive agents.

Because angiotensin-converting enzyme (ACE) inhibitors do not block the formation of angiotensin II mediated by non-ACE enzymatic pathways, such as cardiac chymase, it has been argued that more complete inhibition of the renin-angiotensin system may be beneficial in the setting of congestive heart failure.

Five clinical, controlled studies of heart failure were submitted by Novartis for review. Hemodynamic effects were demonstrated, especially on pulmonary capillary wedge pressure and blood pressure, but in 2 trials, no improvement in exercise performance or symptom benefit was achieved.

The committee deliberations were directed primarily toward the large Valsartan Heart Failure Trial (Val-HeFT) of 5010 patients with class II to IV heart failure who all received some or all of currently accepted therapy, including ACE inhibitors, diuretics, digoxin, and ß-blockers (randomization was stratified by ß-blocker use) and were randomized to placebo or valsartan beginning at a dose of 40 mg BID with forced titration to 160 mg BID. The study assumed a placebo mortality of 12% per year and was powered to detect a 20% reduction in mortality. The trial had 2 coprimary end points, time to death and time to the first morbid event, which included death, sudden death with resuscitation, need for intravenous inotropic or vasodilator agents . . . [Full Text of this Article]