Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training - HF-ACTION

Jun 28, 2022
Font Size
A
A
A
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Heart, Lung, and Blood Institute. Additional studies funded by GE Healthcare and Roche Diagnostics.
Date Presented:
11/13/2008
Date Published:
05/26/2022
Date Updated:
06/28/2022
Original Posted Date:
04/24/2009
References

Contribution To Literature:

Highlighted text has been updated as of June 28, 2022.

The HF-ACTION trial showed that a prescribed exercise training program in patients with chronic symptomatic systolic CHF is safe, with a modest reduction in clinical events, when added to optimal medical therapy.

Description:

Although it is well known that exercise training is associated with an increase in exercise capacity, improved quality of life, and possibly an increased survival, data on exercise training in chronic systolic congestive heart failure (CHF) are sparse. Accordingly, the goal of the HF-ACTION trial was to conduct a randomized trial to compare the safety and efficacy of an exercise training program in patients with New York Heart Association (NYHA) class II-IV systolic CHF, with usual medical care.

Study Design

  • Randomized
  • Parallel
  • Patients enrolled: 2,331
  • New York Heart Association (NYHA) class: II (63%), III (36%), IV (1%)
  • Median follow-up: 2.5 years
  • Mean patient age: 59 years
  • Percentage female: 29%
  • Mean left ventricular ejection fraction (LVEF): 25%

Inclusion criteria:

  • Chronic heart failure (CHF)
  • NYHA class II-IV
  • LVEF <35%
  • Optimal medical therapy
  • Capable of exercising

Exclusion criteria:

  • Already exercising >1 time/week
  • Major vascular event or procedure within the preceding 6 months
  • Patients in whom it was deemed that exercise may be unsafe

Primary Endpoints:

  • All-cause mortality and hospitalizations

Secondary Endpoints:

  • CV mortality and CV hospitalization
  • CV mortality and CHF-related hospitalization
  • Mortality
  • Safety
  • Physiologic endpoints: exercise capacity and 6-minute walk test
  • Quality of life
  • Cost

Drug/Procedures Used:

Patients in the exercise training arm had to complete 36 sessions (3 sessions/week) over 12 weeks, with a goal of about 90 minutes/week, and attainment of 70% of their heart rate reserve. During the maintenance phase, they had to continue with a home exercise regimen, which was comprised of exercise for at least 40 minutes daily, 5 times a week, with attainment of 60-70% of their heart rate reserve. Patients in the usual care arm were recommended to undergo moderate intensity activity 30 minutes/day, but there was no supervision.

Concomitant Medications:

Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (94%), beta-blockers (94%), aldosterone antagonists (45%), loop diuretics (78%), digoxin (45%), implantable cardioverter defibrillator (ICD) (40%), and BiV pacer (18%)

Principal Findings:

A total of 2,331 patients were randomized, 1,159 to the exercise training arm, and 1,172 to the usual medical care arm. Baseline characteristics were fairly similar between the two arms. The baseline left ventricular ejection fraction (LVEF) was about 25%, and the majority of patients had NYHA class II symptoms. CHF was ischemic in etiology in about 51% of the patients. Peak VO2 was about 14.5 ml/min/kg, and the average cardiopulmonary exercise (CPX) duration was about 9.6 minutes. In the exercise training arm, the median duration of exercise was highest during the first couple of months, and had decreased to about 50% by the end of 3 years.

There was no difference between the two arms in the incidence of the primary outcome of all-cause mortality or hospitalization (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.84-1.02, p = 0.13). On adjustment of four important prognostic factors (exercise capacity, LVEF, Beck depression inventory, history of atrial fibrillation or flutter), there was an 11% reduction in the incidence of the primary endpoint in the exercise training arm compared with the usual therapy arm (HR 0.89, 95% CI 0.81-0.99, p = 0.03).

The secondary endpoint of CV mortality and CHF hospitalizations was also not significant between the two arms (p = 0.06), but after adjustment for the above four variables, was significantly lower in the exercise training arm (HR 0.85, 95% CI 0.74-0.99, p = 0.03). The endpoint of CV mortality and CV hospitalization was similar on unadjusted (p = 0.14) and adjusted (p = 0.09) analyses. The overall 3-year mortality was about 16%, with no difference between the two arms (HR 0.96, 95% CI 0.79-1.17, p = 0.70).

At the end of 12 months, there was no difference between the two arms in the 6-minute walk distance (13 m vs. 12 m, p = 0.26). However, CPX duration (1.5 minutes vs. 0.2 minutes, p 2 (0.7 vs. 0.1 ml/min/kg) were higher in the exercise training arm compared with the usual care arm.

Serious adverse events were similar between the two arms, including at least one ICD firing (22% vs. 23%), hospitalization after physical activity (3% vs. 2%), and hospitalization for fracture of hip or pelvis (0.3% vs. 0.6%) (p > 0.05 for all).

On subgroup analysis, it appeared that a higher dose of beta-blockers had a significant inverse relationship with all-cause mortality or hospitalization (HR 0.87, 95% CI 0.77-0.99, p = 0.03), and not a lower heart rate by itself.

Impact of frailty: Frailty was defined using the Rockwood frailty index, with scores >0.21 constituting frailty; 59% of the study cohort met this definition. Baseline frailty burden significantly modified the treatment effect of aerobic exercise training (p for interaction = 0.04) with a lower risk of the primary endpoint of all-cause hospitalization and mortality in frail (HR 0.83, 95% CI 0.72-0.95) but not nonfrail (HR 1.04, 95% CI 0.87-1.25) participants. This benefit among frail patients was particularly driven by a reduction in all-cause hospitalizations.

Interpretation:

The results of the HF-ACTION trial indicate that a prescribed exercise training program in patients with chronic symptomatic systolic CHF is safe, with a modest reduction in clinical events, when added to optimal medical therapy. Although the endpoints of the trial did not meet true statistical significance, when adjusted for four confounders, they were significantly reduced in the exercise training arm compared with the usual therapy arm. In addition, baseline frailty appeared to be an important effect modifier for the primary endpoint, and may help identify HF patients who may benefit more from supervised exercise training. 

One of the biggest limitations of this trial is the difficulty to assess adherence in both groups (lower than prescribed in the exercise training arm, and possibly higher than expected in the usual therapy group), and this may be the result of their neutral finding in the unadjusted analysis. This trial also does not help answer the question regarding the best form of exercise for these patients. A cost-effectiveness analysis of utilizing such an exercise training program is also necessary. However, this trial strengthens current recommendations for exercise in patients with heart failure.

References:

Pandey A, Segar MW, Singh S, et al. Frailty Status Modifies the Efficacy of Exercise Training Among Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the HF-ACTION Trial. Circulation 2022;May 26:[Epub ahead of print].

Fiuzat M, Wojdyla D, Pina I, Adams K, Whellan D, O’Connor CM. Heart Rate or Beta-Blocker Dose? Association With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction: Results From the HF-ACTION Trial. JACC Heart Fail 2016;4:109-15.

O'Connor CM, Whellan DJ, Lee KL, et al., on behalf of the HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439-50.

Presented by Dr. David Whellan at the American Heart Association Annual Scientific Sessions, New Orleans, November 2008.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Exercise

Keywords: Depression, Quality of Life, Exercise Therapy, Heart Failure, Stroke Volume, Atrial Fibrillation, Heart Rate, Frailty


< Back to Listings