BACKGROUND: The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness (VO2peak) and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on VO2peak and 6 minute walk distance (6MWD). METHODS AND RESULTS: In this 24 week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work-to-recovery protocols: 30 to 60 and 120 to 180 seconds. VO2 and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in VO2peak and 6MWD. Assessors were blinded to the treatment group for VO2peak but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait-economy, 10 meter gait-velocity, balance, stair-climb performance, strength, and quality-of-life. Among 47 participants randomized to either MICT (n = 23) or HIIT (n = 24) (mean age 62 +/- 11 years; 81% men), 96% completed training. In intention-to-treat analysis, change in VO2peak for MICT versus HIIT was 2.4 +/- 2.7 versus 5.7 +/- 3.1 mL/kg/min (mean difference 3.2 (95% CI 1.5 to 4.8); p < 0.001), and change in 6MWD was 70.9 +/- 44.3 versus 83.4 +/- 53.6 m (mean difference 12.5 (95% CI -17 to 42); p = 0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference 2.07 mL/kg/min (95% CI 0.59 to 3.6); p = 0.008). No other between-group differences were observed. During VO2 monitoring at 8 and 24 weeks, MICT reached 84 +/- 14% to 87 +/- 18% of VO2peak while HIIT reached 101 +/- 22% to 112 +/- 14% of VO2peak (during peak bouts). CONCLUSIONS: HIIT resulted in more than a 2 fold greater and clinically important change in VO2peak than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in approximately 3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals. REGISTRATION URL: https://www.clinicaltrials.gov; UNIQUE IDENTIFIER: NCT03006731.

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