Etanercept Passes First Phase Of Testing For CHF Treatment

	June 29, 1999 - The drug etanercept deactivates a
protein called tumor necrosis factor, or TNF, which is 
produced by the body in response to cell damage. Earlier
studies had established TNF as one of 3 substances within
the body that worsen heart failure. Researchers doing lab
work found that a certain protein could bind with TNF and
seemed to render it harmless.
	"Current CHF meds block the other 2 substances:
adrenaline, which makes the heart pump faster (beta-
blockers) and angiotensin, which increases blood pressure
(ACE inhibitors). This is the first attempt to deactivate
the third factor - TNF," says Douglas Mann, the study's
lead investigator, from Baylor School of Medicine.
	Man says, "TNF levels are 7-8 times higher in
people with congestive heart failure than in those with
normal hearts. Since in laboratory animals TNF alone can
produce many symptoms of congestive heart failure, it 
seems likely that it would play a major role."
	Twelve heart failure patients received a single dose
(intravenous) containing varying amounts of etanercept,
while 6 similar patients took a placebo. None of the
etanercept patients reported any side effects during the 2
weeks they were tracked, and their TNF levels dropped.
	The 2 highest doses of etanercept were associated
with an improvement in quality of life scores, an improvement
in exercise tolerance and an increase in ejection fraction, in
people in the study.
	This study gives a green light to proceed with a large-
scale clinical trial to test whether a such a drug (cytokine
antagonist) as etanercept might stop disease progression in
heart failure.
	Dr. Mann said, "This will not lead to a cure for heart
failure, because blocking one biological agent, like TNF, seems
to stimulate others, like aldosterone, to become active. But it
will lead to significant improvements in quantity and quality
of life for failure patients."
	Clinical studies of etanercept involving more people
with heart failure are already underway in North America and
Europe, according to Mann. "Heart failure patients should take
as a positive sign the fact that we expect to have the results
of these trials by the end of next year."

Circulation 1999;99:3213-3214,3224-3226