Exercise training improves clinical outcome in women, but not men, with heart failure

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

Literature - Piña IL et al. JACC Heart Fail. 2014 - JACC Heart Fail. 2014 Apr;2(2):180-6

Piña IL, Bittner V, Clare RM; HF-ACTION Investigators.
JACC Heart Fail. 2014 Apr;2(2):180-6


More women than men die of cardiovascular (CV) disease in the United States on a yearly basis, and CV disease is the primary cause of death for American women [1-3]. While the incidence of heart failure (HF) has decreased, hospital admission continues to increase [1,4].
Little evidence from cardiopulmonary testing is available on a beneficial effect of exercise in women with HF. Hence, little is known about whether potential sex differences could affect therapy, functional assessment and recommendations for physical activity and exercise prescription.
The HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial randomised 2331 patients (28% female) with HF (systolic dysfunction: ejection fraction <35%) to a formal exercise program with optimal medical therapy (OMT), or to OMT alone without formal exercise training [4]. Exercise training (ET) was associated with a reduction of the primary endpoint of all-cause mortality or hospital stay [5]. Regular aerobic exercise was found to be safe for patients with HF, and it modestly improves health-related quality of life [6]. A pre-specified primary analysis showed a different risk of the primary endpoint for men and women. This analysis further explores possible sex-specific outcomes of exercise training in men and women with HF.

Main results

  • No differences in change in peak VO2 were seen between men and women in either treatment arm (no significant sex-by-treatment interaction).
  • The target ET for the study was 90 min/week. Adherence to ET was higher among men (45% maintained the goal in the first 3 months, median: 81 min/week) than women (37% maintained the goal, median: 70 min/week).
  • Women randomised to exercise showed a significant reduction of the primary endpoint (HR: 0.74 , 95%: 0.59-0.92), while no such effect was seen in men (HR: 0.99, 95%CI: 0.86-1.13) (significant treatment-by-sex interaction after adjustment, P=0.027).
  • HR for all secondary endpoints was lower in women as compared with men, although the associated treatment-by-sex interactions were not statistically significant.
  • No significant interaction was seen between sex and baseline peak VO2 on the primary endpoint.


In the HF-ACTION trial, the primary endpoint of all-cause mortality or all-cause hospital stay was significantly reduced by 26% in women randomised to exercise training as compared to those who only received optimal medical therapy. This was not seen in men. Thus, a greater reduction in risk with exercise training is seen among women, as compared with men, although no difference in change in peak VO2 was seen between the sexes, and the changes in peak VO2 were modest.
Historically, women were less often referred to and less likely to complete a cardiac rehabilitation programmes. These data suggest that exercise is beneficial in addition to other evidence-based OMT in women with HF.

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1. Koelling TM, Chen RS, Lubwama RN, et al. The expanding national burden of heart failure in the United States: the influence of heart failure in women. Am Heart J 2004;147:74–8.
2. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics: 2010 update: a report from the American Heart Association. Circulation 2010;121:e46–215.
3. Mehta PA, Cowie MR. Gender and heart failure: a population perspective. Heart 2006;92 Suppl 3:iii14–8.
4. American Heart Association. Heart Disease and Stroke Statistics: 2006 Update. Dallas, Texas: American Heart Association, 2006.
5. O’Connor CM, Mentz RJ, Whellan DJ. Covariate adjustment in heart failure randomized controlled clinical trials: a case analysis of the HFACTION trial. Heart Fail Clin 2011;7:497–500.
6. O’Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439–50.
7. Flynn KE, Piña IL, Whellan DJ, et al. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1451–9.

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