Author + information
- Received August 27, 2013
- Revision received October 11, 2013
- Accepted October 15, 2013
- Published online April 1, 2014.
- Ileana L. Piña, MD, MPH∗∗ (, )
- Vera Bittner, MD, MSPH†,
- Robert M. Clare, MS‡,
- Ann Swank, PhD§,
- Andrew Kao, MD‖,
- Robert Safford, MD, PhD¶,
- Anil Nigam, MD, MSc∗∗,
- Denise Barnard, MD††,
- Mary N. Walsh, MD‡‡,
- Stephen J. Ellis, PhD‡,
- Steven J. Keteyian, PhD§§,
- HF-ACTION Investigators
- ∗Division of Cardiology, Montefiore-Einstein Medical Center, Bronx, New York
- †Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
- ‡Duke Clinical Research Institute, Duke University, Durham, North Carolina
- §University of Louisville, Louisville, Kentucky
- ‖University of Missouri–Kansas City, Kansas City, Missouri
- ¶Mayo Clinic, Division of Cardiovascular Diseases, Jacksonville, Florida
- ∗∗Montreal Heart Institute/University of Montreal, Montreal, Quebec, Canada
- ††University of California Health System, San Diego, California
- ‡‡St. Vincent Heart Center of Indiana, Indianapolis, Indiana
- §§Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan
- ↵∗Reprint requests and correspondence:
Dr. Ileana L. Piña, Division of Cardiology, Montefiore-Einstein Medical Center, 111 East 210th Street, Silver Zone 2nd Floor, Bronx, New York 10467.
Objectives 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.
Supported by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received August 27, 2013.
- Revision received October 11, 2013.
- Accepted October 15, 2013.
- American College of Cardiology Foundation