Effects of exercise training on outcomes in women with heart failure: analysis of HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) by sex.
OBJECTIVE
The authors hypothesized that the women enrolled in the HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial and randomly assigned to exercise training (ET) would improve functional capacity as measured by peak oxygen uptake (VO2) compared with those in the usual care group. Furthermore, they hypothesized that the improvement in peak VO2 would correlate with prognosis. They explored whether exercise had a differential effect on outcomes in women versus men.


BACKGROUND
There is less evidence for the benefit of ET in women with heart failure (HF) compared with men because of the small numbers of women studied.


METHODS
HF-ACTION was a randomized trial of ET versus usual care in 2,331 patients with class II-IV HF and a left ventricular ejection fraction of ≤35%. Sex differences in the effects of randomized treatment on clinical outcomes were assessed through the use of a series of Cox proportional hazards models, controlling for covariates known to affect prognosis in HF-ACTION.


RESULTS
Women had lower baseline peak VO2 and 6-min walk distance than did men (median, 13.4 vs. 14.9 ml/min/kg and 353 vs. 378 m, respectively). An increase in peak VO2 at 3 months was present in women and men in the ET group (mean ± SD; median, 0.88 ± 2.2, 0.80 and 0.77 ± 2.7, 0.60, respectively, women vs. men; p = 0.42). Women randomly assigned to ET had a significant reduction in the primary endpoint, (hazard ratio: 0.74) compared with men (hazard ratio: 0.99) randomly assigned to ET, with a significant treatment-by-sex interaction (p = 0.027).


CONCLUSIONS
Although there is no significant difference between men and women in the effect of ET on peak VO2 change at 3 months, ET in women with HF is associated with a larger reduction in rate of the combined endpoint of all-cause mortality and hospital stay than in men.
Division of Cardiology, Montefiore-Einstein Medical Center, Bronx, New York. Electronic address: ilpina@montefiore.org.
Ileana L
IL
Piña
Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.
Vera
V
Bittner
Duke Clinical Research Institute, Duke University, Durham, North Carolina.
Robert M
RM
Clare
University of Louisville, Louisville, Kentucky.
Ann
A
Swank
University of Missouri-Kansas City, Kansas City, Missouri.
Andrew
A
Kao
Mayo Clinic, Division of Cardiovascular Diseases, Jacksonville, Florida.
Robert
R
Safford
Montreal Heart Institute/University of Montreal, Montreal, Quebec, Canada.
Anil
A
Nigam
University of California Health System, San Diego, California.
Denise
D
Barnard
St. Vincent Heart Center of Indiana, Indianapolis, Indiana.
Mary N
MN
Walsh
Duke Clinical Research Institute, Duke University, Durham, North Carolina.
Stephen J
SJ
Ellis
Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan.
Steven J
SJ
Keteyian
D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D012737:Sex Factors; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy
cardiopulmonary exercise testing; exercise training; heart failure; women