The baseline characteristics of HF-ACTION participants by treatment group are shown in . Characteristics were similar between the treatment groups, and the groups had similar mean baseline scores on the KCCQ overall summary scale and key subscales. Furthermore, on the KCCQ symptom stability scale, which measures recent changes in heart failure symptoms such that a score of 50 indicates no recent changes, the mean (SD) scores were 54 (18) in the usual care group and 54 (16) in the exercise group, indicating that participants in both groups were medically stable with respect to heart failure at the time of randomization.
Baseline Characteristics of the Patients by Treatment Groupa
Median follow up was 2.5 years. Visit-level missing data are shown in , accounting for death, withdrawn consent, and visits not expected because of later enrollment in the trial. (Based on randomization date, patients were to be followed for 1 to 4 years before the trial ended.) Because the KCCQ was not administered by telephone, some participants who had telephone follow-up visits are missing KCCQ data over and above the missing visit data. The difference in missing KCCQ data by treatment group did not exceed 6% for any visit.
Patients With Missing Data by Visita
Exercise Training and Patient-Reported Health Status
Results from the mixed models are shown in . All participants who had at least a baseline KCCQ score contributed data to this analysis (1159 in the exercise group, 1171 in the usual care group; ). After adjustment for heart failure etiology, the KCCQ overall summary score improved by 5.2 points in the exercise training group and by 3.3 points in the usual care group from baseline to 3 months. The additional 1.9-point increase in the exercise training group was statistically significant (P < .001). There was no attenuation of this early benefit over time; neither group experienced significant changes in KCCQ scores after 3 months, and there was no significant difference between groups in the slopes over time (P = .85). The overall treatment effect (ie, the difference between overall trajectories by treatment group) was statistically significant (P = .001). This relationship is displayed graphically in . Results were similar in the analysis adjusted for the 28 baseline covariates. There were no significant subgroup interactions for age (P = .44), sex (P = .26), race (P = .97), NYHA class (P = .61), heart failure etiology (P = .75), left ventricular dysfunction (P = .06), previous revascularization (P = .84), history of myocardial infarction (P = .08), depression (P = .24), perceived social support (P = .32), or KCCQ score at baseline (P = .24).
Estimated Changes in Patient-Reported Health Status by Treatment Groupa
Flow of Participants Through the Trial
Predicted Average Health Status Trajectories by Treatment Group Note: P = .001 for treatment effect for both ischemic and nonischemic heart failure. Error bars indicate SEs at each time point.
Results for the KCCQ subscales were similar to the results for the overall summary scale. After adjustment for heart failure etiology, there was a significant overall treatment effect on physical limitations (P < .001), symptoms (P = .02), quality of life (P < .001), and social limitations (P = .02). For these 4 subscales, additional early improvements in the exercise training group compared with usual care were significant (2.3 points on physical limitations, P < .001; 1.5 points on symptoms, P < .001; 1.6 points on quality of life, P = .02; and 1.8 points on social limitations, P = .02). After 3 months, both groups experienced similar slight decreases in physical limitations scores (0.06 points per month for usual care vs 0.05 points per month for the exercise group; difference of 0.006 not significant at P = .84) and slight increases in quality-of-life scores (0.08 points per month for usual care vs 0.09 points per month for the exercise group; difference of 0.02 not significant at P = .60). There were no significant changes in symptoms (P = .91) or social limitations (P = .12) scores after 3 months.
Exercise Training and the Proportion of Patients Benefiting
shows the distribution of predicted changes in the KCCQ overall summary score from baseline to 3 months. In this post hoc analysis, 54% (n = 621; 95% CI, 51%–56%) of patients in the exercise group had a clinically noticeable improvement of ≥ 5 points compared with 29% (n = 334; 95% CI, 26%–31%) of patients in the usual care group (P < .001). (In the analysis adjusted for 28 covariates, the percentages were 52% [n = 602; 95% CI, 50%–55%] and 32% [n = 378; 95% CI, 30%–35%], respectively.) Given the difference in the proportion of patients who experienced a clinically noticeable improvement in health status (26%), the number of well-medicated patients with class II to IV heart failure who would need to be referred to exercise training for 1 patient to benefit significantly more by 3 months than if all patients received usual care alone is 4 (in the adjusted analysis, 5). At 12 months, 53% (n = 618; 95% CI, 50%–56%) of patients in the exercise training group had a clinically noticeable improvement from baseline compared with 33% (n = 386; 95% CI, 30%–35%) in the usual care group (P < .001), suggesting a number needed to treat of 5. (In the adjusted analysis, the percentages were 53% (n = 614; 95% CI, 51%–56%) and 34% (n = 395; 95% CI, 31%–36%), resulting in a number needed to treat of 5.)
Distribution of Predicted Change From Baseline to 3 Months in the KCCQ Overall Summary Score by Treatment Group Note: Bin size = 2. The bin centered over zero ranges from greater than −1 to 1.
Relationship Between KCCQ and Physiologic Outcomes
Changes from baseline to 12 months in the KCCQ overall summary score were associated with changes in exercise time on the cardiopulmonary exercise test (r = 0.28; P < .001), peak oxygen consumption (r = 0.21; P < .001), and 6-minute walk distance (r = 0.18; P < .001). Based on these relationships, an individual’s change of 5 points on the KCCQ overall summary score corresponded to a 1.7-minute change in exercise time, a 1.4-mL/min/kg change in peak oxygen consumption, and a 49.7-m change in distance walked.