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Working out on a stationary bicycle or walking on a
treadmill just 25 to 30 minutes most days of the week is enough
to modestly lower risk of hospitalization or death for patients
with heart failure, say researchers from Duke Clinical Research
Institute (DCRI).

The findings stem from the HF-ACTION trial (A Controlled
Trial Investigating Outcomes Exercise TraiNing), the most
comprehensive study to date examining the effects of exercise
upon patients with heart failure. The study was reported today
as a late-breaking clinical trial at the American Heart
Association's Scientific Sessions 2008 by Christopher O'Connor
M.D., director of the Duke Heart Center and principal
investigator of the trial, and David Whellan, M.D., of Thomas
Jefferson University, co-principal investigator.

HF-ACTION enrolled 2331 patients at 82 study sites
throughout the U.S., Canada and France. Patients were
randomized into a group that received usual care or to a group
that received usual care plus an exercise training program that
began under supervision but then transitioned to home-based,
self-monitored workouts.

Researchers hypothesized that participation in an exercise
program would significantly lower the incidence of death and
hospitalization among patients with heart failure.

But based on the protocol-specified initial analysis,
exercise training produced only a modest, non-significant
reduction in the primary endpoint of all-cause hospitalization
or all-cause death.

A planned, secondary analysis, however, that took into
account the strongest clinical factors predicting
hospitalization or death, found exercise to be significantly
beneficial.

Researchers hope the findings will finally put to rest
long-held fears that exercise may be too risky for some
patients. "The most important thing we found from this study is
that exercise is safe for patients with heart failure, and when
adjustments were made for specific baseline characteristics, it
significantly improved clinical outcomes," said O'Connor.

Whellan, who is also director of clinical research at the
Jefferson Heart Center, says previous studies sent mixed
signals, due, in part, to their small size. Some found exercise
beneficial, but others did not, and there was limited safety
data. "It took a study of this size and duration to determine
that exercise is not only safe, but also effective in lowering
risk of hospitalization or death for patients with heart
failure."

Clinical guidelines say exercise should be considered for
stable patients with heart failure, but the lack of definitive
data about its long-term benefits has limited Medicare and
other insurers from considering an intervention that should be
covered.

Participants in HF-ACTION had a significant degree of heart
failure, determined by left ventricular ejection rate (LVEF), a
measure of how vigorously the heart pumps blood throughout the
body. The patients' mean LVEF was 25; a value less than 35 is
considered problematic. And they were already receiving optimal
care. Ninety-five percent were taking medications for heart
failure, such as ACE-inhibitors or beta-blockers, and 45
percent were using mechanical devices to boost their hearts'
ability to pump or to treat arrthymias. The average age of the
patients was 59 and almost one-third of them were women.

"These patients were quite sick and were receiving
exceptionally good care. That makes the gains they made in the
exercise program all the more remarkable," said Whellan.

Patients in the exercise arm started out slowly, with a goal
of three, 30-minute workout sessions three times per week.
After 18 sessions, they transitioned to workouts at home, with
a goal of 40 minutes five days per week on a stationary bicycle
or treadmill. Patients kept logs of their exercise times and
heart rates.

In contrast, patients in the usual care arm continued their
usual medical therapy and were simply encouraged to be active.
Members of both groups received education about the value of
exercise and supportive phone calls.

Investigators followed the patients for an average of two
and half years, tracking various clinical measures of heart
failure, quality of life, hospitalization, cardiac events and
death rates.

During the study, 796 (68 percent) of patients in the usual
care arm died or were hospitalized, compared to 759 (65
percent) in the exercise arm. There were 198 deaths (17
percent) among patients in the usual care arm, compared to 189
(16 percent) in the exercise arm.

In adjusting for clinical characteristics strongly
predictive of outcomes, including history of atrial
fibrillation, depression, LVEF status, and the patients'
initial capacity for exercise, investigators found that
exercise led to a significant 11 percent reduction in risk of
hospitalization or death for those in the exercise group
(p =.03).

They also found that those in the exercise group had a
significant, 15 percent lower risk of death from cardiovascular
disease and hospitalization due to complications of heart
failure (p = .03), a secondary end point of the
study.

"We feel these are important findings for patients and
physicians alike," said Whellan. "It takes a lot of time and
commitment to definitively answer a question that many of us
had asked for years: Can exercise provide clinically
significant benefit for patients with heart failure? Now we
know that the answer is ‘yes.' We also know that it is safe:
There was no significant difference between the two study
groups in the risk of heart attacks, arrhythmias, falls or
fractures during the study period."

Investigators say there are some limitations to the study.
The benefit of exercise may have been diminished somewhat by
the fact that there was a sizable number of patients randomized
to the usual care arm who actually decided to exercise on their
own.

Researchers say there is important work that still needs to
be done. "HF-ACTION was comprehensive and carefully conducted
study that answered an important clinical question for all of
us," says O'Connor. "But at the same time, it raises new ones:
How will physicians incorporate these findings into their
practice, and how will these programs be paid for? We are
working on a cost/benefit analysis we hope will help answer
some of these questions."

"This study has important implications for the 5 million
Americans who have heart failure," noted Elizabeth G. Nabel,
MD, director of the National Heart, Lung, and Blood Institute
of the National Institutes of Health, which funded the $37
million study. "As the number of people affected by heart
failure is expected to rise with the aging U.S. population, it
is promising to know that patients can benefit from a low-risk
method to improve their health."

Additional co-authors include Kerry Lee, Stephen Ellis,
William Kraus, James Blumenthal, David Rendall and Kevin
Schulman, from Duke; Steven Keteyian, from Henry Ford Hospital,
Detroit; Lawton Cooper, Eric Leifer and Jerome Fleg from the
National Heart, Blood, and Lung Institute; Dalane Kitzman, of
the Wake Forest School of Medicine; Nancy Houston-Miller, from
Stanford University; Robert McKelvie, from Hamilton Health
Sciences Corporation, Ontario, Canada; Faiez Zennad, of the
Centre d'Investigations Cliniques, Nancy, France; and Ileana
Piña, of Case Western Reserve University.