Comparing 6-minute walk versus treadmill walking distance as outcomes in randomized trials of peripheral artery disease

Abstract

Background: Randomized trials of people with peripheral artery disease (PAD) and intermittent claudication have traditionally used maximal treadmill walking distance as the primary outcome, but the 6-minute walk test is increasingly used as a primary outcome in randomized trials of PAD. This study compared relative changes in maximal treadmill walking distance versus 6-minute walk distance in response to a therapeutic intervention or control in randomized trials of participants with PAD.

Methods: Data from four randomized trials of therapeutic interventions in participants with PAD that measured both 6-minute walk and treadmill walking performance at baseline and the 6-month follow-up were combined. Two trials studied supervised treadmill exercise, one studied home-based walking exercise, and one studied resveratrol.

Results: Of 467 participants (mean age, 69.8; standard deviation, 9.7), the mean ankle-brachial index was 0.66 (standard deviation, 0.17). At the 6-month follow-up, participants with PAD randomized to control or placebo significantly declined in 6-minute walk distance (-10.2 m; 95% confidence interval, -18.2 to -2.2; P = .013), but improved maximal treadmill walking distance (+25.7 m; 95% CI, +6.0 to +45.3 m; P = .010; difference between change in 6-minute walk versus maximal treadmill walking distance: -37.3 m; 95% CI, -56.4 to -18.2; P < .001). Home-based exercise improved the 6-minute walk distance by 43.2 m (95% CI, +28.4 to +57.9), and supervised treadmill exercise improved the 6-minute walk distance by 25.0 m (95% CI, +14.7 to +35.2; mean difference, +18.2 m favoring home-based exercise [95% CI, +0.2 to +36.2 m; P = .048]). Among all participants, the presence (vs absence) of treadmill exercise training was associated with a 141.3-m greater improvement in maximal treadmill walking distance compared to 6-minute walk distance (95% CI, 88.2-194.4; P < .001), suggesting a benefit from treadmill training on the treadmill outcome.

Conclusions: Maximal treadmill walking distance and the 6-minute walk distance are not interchangeable outcomes in participants with PAD. Participants with PAD randomized to control groups improved treadmill walking distance but simultaneously meaningfully declined in 6-minute walk distance. Supervised treadmill exercise training amplified improvement in treadmill walking distance because of a training to the outcome measure phenomenon.

Keywords: 6-Minute walk; Clinical trials; Disability; Functional status; Peripheral artery disease.

Figure 1.

Overview of included studies and number of participants

Figure 2A.

Six month absolute changes in six-minute walk distance and treadmill walking performance at six-month follow-up among peripheral artery disease patients randomized to a control group in four randomized clinical trials.

Figure 2B.

Six month percent changes in six-minute walk distance and treadmill walking performance at six-month follow-up among peripheral artery disease patients randomized to a control group in four randomized clinical trials.

Figure 3.

Difference in change in six-minute walk and maximal walking distance at 6-month follow-up among peripheral artery disease patients randomized to a control group

Figure 4a.

Simultaneous changes in six-minute walk distance and treadmill walking performance at 6-month follow-up among PAD participants randomized to either a home-based exercise intervention or a supervised treadmill exercise intervention

Figure 4b.

Difference in change of six-minute walk distance vs. change in maximal treadmill walking distance in PAD participants randomized to either a supervised treadmill exercise intervention or a home-based exercise intervention.