Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.
BACKGROUND
Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes.


OBJECTIVE
To test the efficacy and safety of exercise training among patients with heart failure.


METHODS
Multicenter, randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months.


METHODS
Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone.


METHODS
Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization.


RESULTS
The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Heart failure etiology was ischemic in 51%, and median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 patients (65%) in the exercise training group died or were hospitalized compared with 796 patients (68%) in the usual care group (hazard ratio [HR], 0.93 [95% confidence interval {CI}, 0.84-1.02]; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 patients [16%] in the exercise training group vs 198 patients [17%] in the usual care group; HR, 0.96 [95% CI, 0.79-1.17]; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise training group vs 677 [58%] in the usual care group; HR, 0.92 [95% CI, 0.83-1.03]; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise training group vs 393 [34%] in the usual care group; HR, 0.87 [95% CI, 0.75-1.00]; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81-0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82-1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74-0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups.


CONCLUSIONS
In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.


BACKGROUND
clinicaltrials.gov Identifier: NCT00047437.
O'Connor
Christopher M
CM
Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715, USA. oconn002@mc.duke.edu
Whellan
David J
DJ
Lee
Kerry L
KL
Keteyian
Steven J
SJ
Cooper
Lawton S
LS
Ellis
Stephen J
SJ
Leifer
Eric S
ES
Kraus
William E
WE
Kitzman
Dalane W
DW
Blumenthal
James A
JA
Rendall
David S
DS
Miller
Nancy Houston
NH
Fleg
Jerome L
JL
Schulman
Kevin A
KA
McKelvie
Robert S
RS
Zannad
Faiez
F
Piña
Ileana L
IL
D000368:Aged; D000553:Ambulatory Care; D002908:Chronic Disease; D015444:Exercise; D005081:Exercise Therapy / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000534:rehabilitation*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011788:Quality of Life; D012648:Self Care