• Multicenter, unblinded randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction.
• Participants were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France.
• The primary end point was a composite of all-cause mortality or all-cause hospitalization.
• Secondary end points included all-cause mortality, the composite of cardiovascular mortality or cardiovascular hospitalization, and the composite of cardiovascular mortality or heart failure hospitalization.

• Major comorbidities or limitations that could interfere with exercise training, recent (≤6 weeks) or planned (≤6 months) major cardiovascular events or procedures, performance of regular exercise training, or use of devices that limited the ability to achieve target heart rates.

• Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone.
• Patients randomized to the exercise training arm first participated in a structured, group-based, supervised exercise program, with a goal of 3 sessions per week for a total of 36 sessions in 3 months (walking, treadmill, or stationary cycling as their primary training mode). Exercise was initiated at 15 to 30 minutes per session at a heart rate (HR) corresponding to resting HR plus 60% of HR reserve (HRR), defined as maximal HR on cardiopulmonary exercise test minus resting HR. After 6 sessions, the duration of the exercise was increased to 30-35 minutes and intensity was increased to Resting HR plus 70% of HRR. Patients then began home-based exercise after completing 18 supervised sessions and were to fully transition to home exercise after 36 supervised sessions. The target training regimen for home exercise was 5 times per week for 40 minutes at a HR of 60%-70% of HRR + resting HR.

Primary Endpoints

• The median age was 59 years, 28% were women, and 37% had NYHA 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).

Secondary Outcomes

• There were non-significant 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 analyses, after adjusting for 5 highly prognostic baseline variables (duration of the cardiopulmonary exercise test, LVEF, Beck Depression Inventory II score, history of atrial fibrillation or flutter, and HF etiology), exercise training was found to reduce the incidence of all-cause mortality or all-cause hospitalization (the primary end point) by 11% (hazard ratio, 0.89; 95% CI, 0.81-0.99; P =0.03).
• Other adverse events were similar between the groups.

• HF-ACTION is the largest multicenter, randomized controlled trial of exercise training in heart failure at the time of publication.
• This trial demonstrated that regular exercise training in patients with systolic heart failure was safe.
• Exercise training conferred modest and statistically significant improvements in self-reported health status compared with usual care without training. Improvements occurred early and persisted over time.
• Findings from HF-ACTION are consistent with the 33 previous trials and the Cochrance systemic review showing improved outcomes.
• Although the rate of all-cause hospitalization was not reduced, exercise training was associated with a 28% reduction in HF-related hospitalizations and improvement in health-related quality of life.
• Based on the safety of exercise training and the modest reductions in clinical events in addition to the modest increases in health-related quality of life, the HFACTION results support a prescribed exercise training program for patients with reduced left ventricular function and heart failure symptoms in addition to evidence-based therapy.