By Amy Norton, Medical Tribune News Service
A drug used for rheumatoid arthritis has pointed the way to a
new approach in treating congestive heart failure, according to a
report out Tuesday.
This approach aims to halt the progression of heart failure by
inactivating an immune-system protein called tumor necrosis factor
(TNF). TNF, which is key to the body's inflammatory process, is
known to play a role in rheumatoid arthritis; animal studies
conducted since 1990 have shown that TNF may also worsen heart
failure.
In heart failure, the heart fails to pump enough blood to meet
the body's needs. Marked by shortness of breath, fatigue and
swelling of the feet and legs, the disease usually results from a
heart attack, high blood pressure, a congenital defect in the heart
or an infection that weakens the heart muscle. The prognosis for
the disease is poor; among patients with advanced heart failure,
about 30 percent die within a year.
Current heart-failure drugs target substances such as
angiotensin and adrenaline, which affect blood-vessel constriction
and dilation, noted Dr. Douglas Mann, chief of cardiology at
Houston V.A. Medical Center.
Despite these drugs, heart failure remains ``relentlessly
progressive'' in patients, indicating that other mechanisms must
also govern the disease, according to Mann.
``Our research suggests that TNF is one of those molecules,'' he
said.
In a study of 18 patients with severe heart failure, Mann's team
found that an infusion with the anti-TNF drug etanercept _ recently
approved for severe rheumatoid arthritis _ cut the TNF levels in
their blood and strengthened their hearts' pumping over a two-week
period. Their findings appear in Circulation: Journal of the
American Heart Association (www.circulationaha.org).
Researchers believe that inhibiting TNF may effectively treat
heart failure because animal research has shown that the protein
spurs dilation of blood vessels in the heart, lessens its pumping
capacity, degrades its connective tissue and kills heart-muscle
cells.
Further, Mann noted, heart-failure patients have been found to
have seven to eight times the TNF level in the blood of people with
healthy hearts. He estimated that 85 percent of people with
advanced heart failure have elevated TNF levels.
The only way to show whether TNF-inhibition might help
heart-failure patients is to observe the effects of a drug like
etanercept. In Mann's study, the 12 patients who received the drug
improved their walking distance in tests, showed better heart
pumping strength and reported improved quality of life. The six who
received a placebo showed no changes over the two-week study
period.
All of the patients were already being treated with an ACE
inhibitor medication -- the first-line treatment for heart failure
that lowers blood pressure by blocking angiotensin. Some were on
other heart-failure drugs in addition.
The success of TNF inhibition in this study offers ``proof of
principle'' that should fuel research into whether anti-TNF drugs
should enter the heart-failure arena, according to Mann.
``This is exciting news for physicians and patients,'' said Dr.
Gary S. Francis, director of the coronary intensive care unit at
the Cleveland Clinic Foundation in Ohio.
TNF inhibition, he noted, follows the same principle as drugs
like ACE inhibitors and beta blockers. ``Blocking TNF is a narrower
focus,'' he said. That etanercept improved ``surrogate outcomes''
like walking distance and quality of life suggests that TNF
inhibition may help prolong patients' lives, according to Francis.
Larger trials are underway to address whether the agents should
be added to standard heart-failure treatment. Mann predicted that
this research will yield definitive results by the end of next
year.
