ACC 2009: HF-ACTION on Exercise Training in Heart Failure: Refrain, No Gain

April 07, 2009

April 7, 2009 (Orlando, Florida) — Patients with chronic heart failure who enter into an exercise training program may have only a modestly better survival and lower hospitalization risk than those who aren't prescribed exercise, but they are significantly more likely to feel in overall better health [1], concludes a randomized study that also suggests a training regimen can be safe in such patients and that they more they stick with it, the better their clinical outcomes are likely to be.

In a follow-up analysis from Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), which had randomized heart-failure patients to follow or not follow an exercise-training program, every metabolic-equivalent-tasks (MET)-hour/week increment in achieved exercise intensity produced a 5% reduction in the 90-day risks of both death/hospitalization and CV death/CV hospitalization (p=0.003 and p=0.009, respectively). The same step up in exercise volume also translated into significant gains in peak VO2, six-minute-walk distance, and health status as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ).

"This analysis quantifies the dose-response relationship between regular aerobic exercise and patient outcomes among subjects in HF-ACTION," said Dr Steven J Keteyian (Henry Ford Hospital, Detroit, MI) in a presentation here at the American College of Cardiology (ACC) 2009 Scientific Sessions. "It appears that only a modest amount or dose of exercise is needed to potentially improve or impact risk."

Hazard Ratio (95% CI) for Clinical Composite End Points for Every 1 MET-Hour/Week* Gain Over 90 Days

End point HR (95% CI) P
All-cause death or hospitalization 0.95 (0.92-0.98) 0.003
CV death or CV hospitalization 0.95 (0.92-0.99) 0.009
CV death or HF hospitalization 0.89 (0.84-0.94) <0.0001
*Exercise intensity, MET=metabolic equivalent tasks

That dose-response relationship, he explained, may have been a big influence on the trial's previously reported primary outcome, that exercise training had no significant effect on death or hospitalization from any cause over a median follow-up of 30 months.

There were suggestions of significant exercise effects in prospectively defined secondary analyses, however, that have led many to take a positive message from the trial regarding exercise in heart failure.

Those primary findings, which had been presented at the American Heart Association 2008 Scientific Sessions and covered by heartwire at the time, are now published in the April 8, 2009 issue of the Journal of the American Medical Association.

The apparent implication of Keteyian's report at the ACC sessions, however, is that exercise training might well have improved patient outcomes in a more statistically solid way had the group adhered more closely to the program. Or, it may imply, gains from exercise could have been more pronounced among patients who adhered closely to their prescribed exercise regimens compared with those who didn't.

In a separate prospectively defined analysis published alongside the primary HF-ACTION report [2], the patients randomized to exercise showed "modest but statistically significantly improvements" (p<0.001) in health-status scores on the KCCQ over the trial's first three months. Those improvements were apparently sustained throughout the trial's entire follow-up time.

Overall, HF-ACTION had randomized 2331 stable patients with systolic heart failure to usual care with or without an aerobic exercise training program that included 36 supervised sessions followed by participation in a home-based regimen using exercise equipment provided to them.

When I came into cardiology in the early 70s, we discouraged exercise in heart-failure patients.

As published with lead author Dr Christopher M O'Connor (Duke Clinical Research Institute, Durham, NC) and previously reported, there was no significant difference between 1172 usual-care-only patients and the 1159 prescribed exercise in the primary end point of death or hospitalization from any cause, for a hazard ratio of 0.93 (95% CI, 0.84–1.02; p=0.13) over a median follow-up of 30 months.

Nor were there significant effects on the secondary end points of CV mortality/CV hospitalization or CV mortality/HF hospitalization.

After adjustment for "highly prognostic baseline characteristics," including LVEF, reductions in two of the HRs became significant; the p values for all three were p=0.03, p=0.09, and p=0.03, respectively.

In the accompanying report, Dr Kathryn E Flynn (Duke Clinical Research Institute) and associates found that adding exercise training to usual care led to significant improvements in KCCQ scores, overall and in several subscales, during the first 90 days compared with usual care on its own (p<0.001). No further differences were observed at regular intervals throughout the remaining follow-up, suggesting that early gains with exercise were sustained over the long term.

The KCCQ subscales that mirrored the overall score gauged physical limitation, social limitation, symptoms, and quality of life.

"Unlike previous studies suggesting that women and older patients [with systolic heart failure] may not respond as well to exercise training, our findings of exercise-related benefit were relatively consistent across sex, race, age, and other subgroups," Flynn et al write.

The "dose-response" analysis presented at the ACC last week had focused solely on the 959 patients in the exercise group who were event-free at 90 days, a period that, Keteyian said in his presentation, allowed whatever effect exercise training might have on outcomes to take place.

Increments in exercise volume improved objective measures of exercise capacity and KCCQ scores right along with clinical outcomes.

Increases in Measures of Exercise Capacity and Health Status for Every 1 MET-Hour/Week* Gain Over 90 Days

Parameter Change p
Peak VO2 (mL/kg/min) 0.18 <0.0001
6-min-walk distance (m) 4.23 <0.0001
KCCQ score (points) 0.73 <0.001
*Exercise intensity, MET=metabolic equivalent tasks

KCCQ=Kansas City Cardiomyopathy Questionnaire

After Keteyian's presentation, session comoderator Dr Karl Swedborg (Sahlgrenska University Hospital, Göteborg, Sweden) referred to lingering concerns that exercise might be hazardous for some patients with chronic heart failure. HF-ACTION, he said, helps to "justify" exercise training in heart failure by showing that it is safe. "Which is a major shift in treatment. When I came into cardiology in the early 70s, we discouraged exercise in heart-failure patients."

He also expressed concern about some potential confounders in the trial's "dose-response" analysis, confounders that Keteyian acknowledged. It wasn't prospective or randomized, for example. Also, "we have shown in the CHARM trial that adherence to placebo actually improves survival [3]. So adherence to [any] intervention is important, and probably these patients also took other life-prolonging treatments as well," Swedborg said. "I would guess and would propose to you that these patients who adhered to exercise also adhered to other life-prolonging medications."

HF-ACTION was primarily funded by the National Heart, Lung, and Blood Institute ; ancillary analyses were funded by GE Healthcare and Roche Diagnostics. Keteyian had nothing to disclose. Disclosures for the other coauthors are in the reports.




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