November 11, 2008 (New Orleans, Louisana) — Heart-failure patients participating in a highly structured exercise program in the HF-ACTION trial, reported here at the American Heart Association (AHA) 2008 Scientific Sessions, saw no significant reductions in all-cause mortality or all-cause hospitalization as compared with patients getting "usual care," including recommendations for daily exercise.
But in secondary analyses, where investigators adjusted for what they called the "strongest prognostic factors," the structured-exercise group did show significant reductions in the combined primary end point, as well as in the secondary end point of cardiovascular mortality and heart-failure hospitalization.
On these grounds, co-principal investigator for the study, Dr Christopher O'Connor (Duke University Medical Center, Durham, NC), concluded: "The HF-ACTION study results support a structured exercise training program for patients with reduced LV function and HF symptoms in addition to evidence-based therapy."
HF-ACTION randomized 2331 heart-failure patients (NYHA class 2-4, ejection fraction <35%) to either an exercise program focused on increasing workout intensity and duration or to usual care, in which exercise was simply encouraged, but without specific advice. The structured-exercise group began with 36 supervised training sessions for 30 minutes of exercise three times per week. Halfway through this period, patients were given a treadmill or stationary bicycle to use at home along with a heart-rate monitor and were advised to work out five times per week at moderate intensity for 40 minutes. The usual-care group, by contrast, was told at the study outset to try to exercise at moderate intensity, 30 minutes per day, as recommended by the ACC/AHA, but were not supervised or encouraged along the way
After a mean of 2.5 years, rates of all-cause mortality and all-cause hospitalizations combined were not significantly different between the two groups. In secondary analyses, however, investigators used what they termed prespecified major prognostic factors identified at the outset of the trial--heart-failure etiology, exercise duration, left ventricular ejection fraction, Beck depression inventory, and history of atrial fibrillation/flutter. When the analysis was adjusted for these prognostic factors, the composite primary end point was significantly reduced by 11%, and a composite of cardiovascular mortality/heart-failure hospitalization was reduced by 15%.
Event Rates in Main Analysis and After Adjustment of Prognostic Factors
|End point||Hazard ratio||95%||p|
|CV mortality/CV hospitalizations||0.92||0.83–1.03||0.14|
|CV mortality/HF hospitalizations||0.87||0.75–1.00||0.06|
In a comparison of safety outcomes--such as rates of cardiovascular events, ICD firing, hospitalization for physical activity, or fracture of the hip/pelvis--event rates were very similar between the two groups. "One of the most important findings was that exercise at this level was safe," O'Connor said.
Despite missing its primary end point, said O'Connor, "The HF-ACTION study results support a structured exercise training program for patients with reduced LV function and HF symptoms in addition to evidence-based therapy."
Discussing the results following their presentation, Dr Philip Poole-Wilson (Imperial College London, UK) also took the view that HF-ACTION provides support for a more intense and structured exercise programs.
"Some people would say, well, they missed their primary end point, let's all go home. I think that would be very wrong," he said.
Instead, he said, the adjusted outcomes are "very compelling" and consistent with the findings from exercise tests in the two groups. "I think this trial does support the use of exercise, and it will strengthen the guidelines," he said.
The problem with HF-ACTION, as with every other exercise trial, is that convincing patients to adopt and stick with an intensive exercise program is very difficult. O'Connor told the media that at three years, the median minutes of exercise per week for people in the intensive arm of the study was approximately 50 minutes and the proportion of patients adhering to the recommended 120 minutes per week was just 30%.
"The one thing this trial does not show is what type of exercise to advocate, and I think we're going to see a lot of other studies in that area," Poole-Wilson said. "Not just what sort of exercise, but how do you persuade people with heart failure to exercise and to continue to exercise, so that the effect does not fade simply because the person ceases to exercise?"
Not the Old Silk Purse/Sow's Ear
Some people would say, well, they missed their primary end point, let's all go home.
Challenged during the press conference to explain how a trial that missed its primary end point could be interpreted so positively, O'Connor took pains to distinguish the HF-ACTION results from those of a negative drug trial, where overemphasis on secondary end points is roundly viewed as a no-no.
"This is not a drug, it's a lifestyle intervention, and we know that lifestyle intervention trials are very, very difficult," O'Connor said. "At the end of 2.5 years of a drug trial, you'd have 85% to 95% of the patients still on the drug. In a trial like this, the amount of exercise that people were doing in the exercise-training group after three years was in the order of 50 to 60 minutes; we wanted them at 120 minutes. So adherence is extremely difficult."
Having said that, he continued, the hazard ratios for the primary end point and cardiovascular mortality/heart-failure hospitalizations were very similar for the main results and the adjusted analysis. "In the context of this type of trial, and because it was prespecified, it was a fair analysis," O'Connor said. "It's probably closer to the truth when you compared patients who were alike in risk and low risk and alike in risk and high risk."
Heartwire from Medscape © 2008 Medscape
Cite this: Shelley Wood. AHA 2008: HF-ACTION Misses, But Experts Say Results Support Intensive Exercise in HF Patients - Medscape - Nov 11, 2008.