1 Introduction
Stroke is the leading cause of disability and the third most common cause of death globally, affecting approximately 93.8 million people worldwide, and causing about 160.5 million disability-adjusted life-years lost in 2021 (1). Patients after chronic stroke often face motor impairments, leading to mobility challenges such as walking and balance difficulties (1). Reduced physical activity can further impact cardiorespiratory fitness (CRF), which is defined as the capacity of the circulatory and respiratory systems to supply oxygen to skeletal muscle mitochondria for energy production required during physical activity (2). Patients after stroke typically demonstrate low values of peak oxygen uptake (V̇O2-peak) (3), a key indicator of CRF. Therefore, improving CRF by implementing aerobic training in this population is critical in stroke rehabilitation (4).
Currently, moderate-intensity continuous training (MICT), typically targeting a heart rate of 40–80% of heart rate reserve (HRR), is the most commonly used aerobic training program and is recommended in stroke rehabilitation guidelines (5–7). The benefits of MICT in improving V̇O2-peak, motor function, and cardiovascular risk factors (e.g., blood pressure and glucose levels) are well established (8, 9). However, evidence suggests that the therapeutic effects of aerobic training may be associated with training intensity (10). The intensity of MICT may not sufficiently challenge the cardiovascular system to elicit maximal adaptations, nor meet the threshold required to complete many activities of daily living (10, 11).
Previous studies have proposed the use of high-intensity training (>60% of HRR) could augment outcomes, although such high intensity exercise can be challenging for patients after stroke (12, 13). Therefore, high-intensity interval training (HIIT), a modality that maximizes exercise intensity by alternating bursts of high intensity effort with recovery periods to enable higher sustained intensities at lower perceived exertion than high-intensity continuous exercise, has gained popularity in recent years (14–16).
Several meta-analyses have shown that HIIT leads to significantly better outcomes than MICT in healthy individuals and in patients with chronic diseases such as cancer, obesity, coronary artery disease, and heart failure (17–23). However, few clinical trials have compared the effects of HIIT and MICT in patients after stroke, leaving its therapeutic efficacy unclear. To date, only two meta-analyses have explored the effects of HIIT among patients after stroke. Both of them primarily compared HIIT with control group (usual care) or low-intensity continuous training, which lead to obviously better results (24, 25). With emerging clinical trials that explores the difference between HIIT and MICT in stroke population, we conducted this review study to provide further insight for clinical practice.
In the present study, we aimed to explore the effects of HIIT versus MICT on improving CRF, functional performance in mobility, and the differences in training fidelities between HIIT and MICT.
2 Methods
This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews of the UK National Institute for Health Research (PROSPERO; ID: CRD42025645342), and was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (50).
2.1 Searching strategy
We searched the PubMed, Embase, and Cochrane Library for studies published from inception to February 2025 using the following search terms: ([high-intensity interval training OR HIIT] OR [moderate-intensity continuous training OR MICT] OR aerobic training) AND (stroke OR cerebrovascular accident OR cerebrovascular disorder OR cerebral infarction OR brain infarction OR intracranial arteriosclerosis OR intracranial thrombosis OR intracranial embolism OR CVA). The detailed searching strategy is presented in the Supplementary Data 1. Moreover, all retrieved abstracts, studies, and citations were reviewed. No language restrictions were applied.
2.2 Study inclusion and exclusion criteria
We included randomized trials on the basis of their titles and abstracts in accordance with the following selection criteria: (1) compared the outcomes of HIIT with MICT in patients after stroke, and (2) reported the inclusion and exclusion criteria for patient selection. We excluded trials that (1) were observational or nonrandomized trials, (2) primarily used intervention other than HIIT (ie, high intensity continuous training), (3) compared HIIT with non-MICT intervention (ie, low intensity exercise or usual care), and (4) had not been published as full-text articles in a peer-reviewed journal.
2.3 Data extraction
Two reviewers independently extracted baseline and outcome data, including the number, age, and sex of the participants; inclusion and exclusion criteria; number of patients after ischemic stroke; intervention regimens, frequency, and duration; and outcome parameters. Individually recorded data from two reviewers were compared, and any disagreements were resolved by a third reviewer. In case of missing data or interesting data that were not reported in the article, the corresponding authors of the original study for information were contacted through e-mail.
2.4 Outcomes
The primary outcome was the CRF indicators, including V̇O2-peak (mL/kg/min) or VO2 at ventilation threshold (VO2-VT, mL/kg/min) measured by cardiopulmonary exercise test. Previous studies have determined the minimum detectable change for V̇O2-peak in patients after stroke to be 1 mL/kg/min (26, 27). The secondary outcomes were the functional performance in mobility, involving walking speed (10-meter walk speed), walking endurance (6-min walk test), and postural balance (Berg Balance Score). Resting blood pressure, a cardiovascular risk indicator, was surveyed. In addition, parameters of training fidelity representing the intensity the patient sustained during a training session were included.
2.5 Study quality assessment
The methodological quality of the randomized trials was assessed independently by two reviewers, in accordance with the revised Cochrane Risk of Bias (RoB 2.0) tool, PEDro scale, and the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX).
RoB 2.0 includes the following domain: bias deriving from the randomization process, bias caused by deviations from intended interventions, bias caused by missing outcome data, bias arising from outcome measurement, bias deriving from selection of the reported results, and overall risk of bias (28). Each domain was rated as having low risk of bias, some concerns, or high risk of bias. The PEDro scale assesses the quality of randomized controlled trials in physiotherapy and rehabilitation, focusing on validity, statistics, and design. It includes 11 criteria, with scores below 4 rated as poor, 4–5 as fair, 6–8 as good, and 9–10 as excellent (29). The TESTEX scale is a 15-point scale that is designed specifically for use in exercise training studies, with scores below 6 rated as ‘low quality’, 7–11 as ‘good quality’, and 12–15 as ‘high quality’ (30). After individual assessments, the two reviewers discussed any potential discrepancies, which were subsequently resolved by a third reviewer.
2.6 Data synthesis and presentation
Data were analyzed by Review Manager, Version 5.3 (Cochrane Collaboration, Oxford, England). Standard deviations were estimated from the provided confidence interval (CI) limits or standard errors. For the primary and secondary outcomes, the means and standard deviations of pretreatment–posttreatment changes were used in the meta-analysis. When necessary, these values were estimated in accordance with the reported pretreatment and posttreatment data (31). Continuous outcomes were analyzed using the mean difference (MD) or the standard mean difference (SMD). The precision of the effect sizes was reported as 95% CIs. We used the DerSimonian and Laird random-effects model to compute a pooled estimate of the MD or the SMD (32). The inverse variance method was used to analyze continuous variables. The I2 test was used to quantify the heterogeneity of the outcomes. Heterogeneity was classified as small, moderate, and large for I2 values of 25, 50, and 75%, respectively. Results were reported only when 2 or more studies were available for meta-analysis on the same outcome.
2.7 Assessment of quality of evidence
We used the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach to access the quality of evidence (33). Rating aspects include (1) study limitations, (2) inconsistency, (3) indirectness, (4) imprecision, and (5) publication bias. We consequently graded the quality of evidence for each outcome as high, moderate, low, or very low quality.
3 Results
3.1 Search results and study characteristics
A flowchart describing the screening and selection process is presented in Figure 1. Nine articles involving eight different trials were included in the systematic review and meta-analysis (34–42).
The characteristics of the included trials are summarized in Table 1. Two articles reported different aspects of the same trial; one concerns CRF benefits (40) and the other concerns psychosocial responses (41). Three trials were conducted in Canada (37, 39–41), two in The United States of America (34, 35), one in Pakistan (38), one in South Korea (42), and one in Taiwan (36). Two articles reported different aspects of the same trial; one concerns CRF benefits and the other concerns psychosocial responses after training (40, 41). A total of 371 patients aged from 50 to 80 were included in the meta-analysis.
In the training modality, three trials used treadmill exercise as their HIIT program (34, 35, 39), two trials used bicycle ergometer (36, 37), one trial used adaptive recumbent steppers (40, 41), one trial used lateral push-off skater exercise (42), and the other trial did not provide information regarding training modality (38). The intensity of high-intensity intervals was measured by heart rate (60–100% of HRR) in three trials (34, 35, 40, 41), VO2 (80–100% of V̇O2-peak) in two trials (36, 39), and power output in one trial (37). Two trials did not provide detailed information on defining the intensity of interventions (38, 42), though we have contacted the corresponding authors for more detailed information. Training duration and frequency varied from two to five sessions per week (34–37, 39–42); and the duration of intervention lasted for 4 weeks in one trial (35), 12 weeks in five trials (34, 36, 38, 40–42), and 24 weeks in the other two trials (37, 39).
3.2 Methodological quality
The assessment of ROB 2.0 of the included trials is summarized in Table 2 and Supplementary Figure 1. Overall, one trial was rated as having high risk of bias (38), one trial was rated as having moderate risk of bias (37), and the remaining six trials were rated as having low risk of bias (34–36, 39–42).
The assessment of PEDro scale of the included trials is summarized in Table 1 and Supplementary Table 1. The PEDro scores ranged from four to eight. Most of the trials were downgraded due to lack of subject blinding and therapist blinding. Overall, three trials were rated as having fair methodological qualities (37, 38, 42), and the remaining six trials were rated as having good methodological qualities (34–36, 39–41).
The assessment of the TESTEX scale of the included trials is summarized in Supplementary Table 2. The TESTEX scores ranged from 10 to 15. Overall, two trials were rated as having good methodological qualities (37, 38), and the remaining six trials were rated as having high methodological qualities (34–36, 39–42).
The assessment results of the three assessment tools are generally consistent with each other.
3.3 Effects on CRF outcomes
Effects on V̇O2-peak and VO2-VT were shown in Figure 2. The pooled results from all included studies (34–42) showed that HIIT exhibited a significantly greater improvement in V̇O2-peak than MICT (MD = 1.88 mL/kg/min, 95% CI = 1.20 to 2.55, p < 0.00001; Figure 2A). A sensitivity analysis excluding 2 studies (37, 38) with moderate and high risk showed a similar result (MD = 2.02 mL/kg/min, 95% CI = 1.27 to 2.77, p < 0.00001). In addition, the pooled results from three included studies (34, 35, 39) showed that HIIT exhibited a significantly greater improvement in VO2-VT than MICT (MD = 2.20 mL/kg/min, 95% CI = 0.46 to 3.95, p = 0.01; Figure 2B).
3.4 Effects on functional performance in mobility
The pooled results revealed that there was no significant difference between HIIT and MICT in change in 6-min walk test (MD = 17.63 m, 95% CI = −1.44 to 36.70, p = 0.07; Figure 3A) (34, 35, 38–40), the change in 10-meter gait speed (MD = 0.08 m/s, 95% CI = −0.01 to 0.17, p = 0.08; Figure 3B) (34, 35, 39, 40), or the change in Berg Balance Score (MD = 2.57, 95% CI = −4.53 to 9.68, p = 0.48; Figure 3C) (39, 42).
3.5 Training fidelity regarding the intensity
The pooled results from three studies (34, 35, 39) showed that patients undergoing HIIT sustained greater mean heart rate than MICT during the training session (MD = 19.36% of HRR, 95% CI = 13.83 to 24.90, p < 0.00001; Figure 4A). In addition, patients undergoing HIIT also sustained greater peak heart rate than MICT during the training session (SMD = 1.00, 95% CI = 0.40 to 1.59, p = 0.0010; Figure 4B) (34, 39, 42).
3.6 Effects on resting blood pressure
During the intervention period, no significant differences were observed between HIIT and MICT in systolic blood pressure changes (MD = −1.72 mmHg, 95% CI = −5.92 to 2.48, p = 0.42; Supplementary Figure 2A) (37, 39, 40, 42) and diastolic blood pressure (MD = −1.04 mmHg, 95% CI = −3.78 to 1.69, p = 0.48; Supplementary Figure 2B) (37, 39, 40, 42).
3.7 Adverse effects
No adverse events of HIIT were observed in two of the included studies (37, 42). In another four studies, no study-related serious adverse events occurred, and the number of adverse effects was similar between the HIIT group and the MICT group. Common adverse events included pain, soreness, fatigue, lightheadedness, and fall (34, 35, 39, 40). No information on adverse effects was provided in the other two studies (36, 38).
3.8 Quality of evidence
The summary of findings and the grading of the evidence certainty are presented in Supplementary Table 3. The GRADE certainty of the evidence of the above outcomes were moderate or low because of inconsistency [unexplained heterogeneity was detected in the pooled result (I2 > 50%)] and imprecision (the number of studies and patients are small).
4 Discussion
To the best of our knowledge, this is the first systematic review to directly compare the effects of HIIT and MICT in patients after stroke. Overall, HIIT generated a 1.88 mL/kg/min improvement in V̇O2-peak compared to MICT, which exceeded the reported minimum detectable change (26, 27) (1 mL/kg/min) in patients after stroke. Given that every 3.5 mL/kg/min (equal to 1 metabolic equivalent) increase in V̇O2-peak was associated with a 15 to 20% decrease in overall mortality among various populations (51), a difference of 1.88 mL/kg/min of V̇O2-peak was clinically meaningful. Considering that MICT remained the most commonly used training mode in stroke rehabilitation, our results support the suggestion that HIIT may be also used as an alternative for aerobic training in stroke population.
Previous studies have shown that acute bout of HIIT activates signaling pathways involving mitochondrial biogenesis, and repeated activation of these pathways may lead to specific muscular adaptations, including increased mitochondrial density, capacity and respiration in skeletal muscle (43–45), which is related to improvements in V̇O2-peak. In addition, previous studies have shown that HIIT can lead to better improvements in cardiac contractility, systolic function, and endothelial function in patients with cardiovascular diseases when compared to MICT (21, 46). Moreover, one included study in our meta-analysis also compared the physiological effects of HIIT to those of MICT on patients after stroke, and the results showed that HIIT significantly improved cardiac output (mean improvement: 1.45 L/min, p = 0.038) and serum brain-derived neurotrophic factor level (mean improvement: 1.85 ng/mL, p = 0.012). Improvement in aerobic capacity by increasing systemic tissue oxygen extraction, and increased cerebral oxygen utilization in the involved hemisphere was also observed after HIIT when compared with MICT (36). All these mechanisms discussed above may lead to better improvements in CRF in the HIIT group when compared with the MICT group, which is the primary result in this meta-analysis.
However, our results revealed that HIIT did not result in superior functional mobility improvements, indicating that HIIT is not superior to MICT in those variables. This may be attributed to the relatively small number of included studies assessing these outcomes and the high heterogeneity observed (e.g., I2 = 65% for the 6-min walk test and 94% for the Berg Balance Score), suggesting variability in patient characteristics and intervention protocols. While CRF plays a crucial role in mobility, stroke-related impairments such as neuromuscular dysfunction, reduced motor coordination, muscle weakness, proprioceptive deficits, and impaired balance may limit the direct translation of improved aerobic capacity into functional mobility gains (47). Further research is needed to better understand the effects of HIIT on functional mobility in patients after stroke and to identify factors that may influence its efficacy.
Two recent review studies have addressed the effects of HIIT in the stroke population (24, 25). Although Anjos et al. supported the superiority of HIIT over continuous aerobic training, their conclusion was based on only 4 trials with 91 patients. Moreover, their continuous aerobic training group was mixed with low-intensity walking, which caused bias in interpreting the true difference between HIIT and MICT (24). On the other hand, Moncion et al. conducted a systematic review on the effects of various aerobic exercise interventions (i.e., HIIT, high-intensity continuous training, MICT, low-intensity continuous care, usual care) (25). Their network meta-analysis showed no significant mean difference between HIIT and MICT (i.e., MD = 0.82 mL/kg/min, 95%CI: −0.92 to 2.56). It should be noted that their result was based on only 4 trials involving direct comparison between HIIT and MICT. Additionally, the methodological bias arising from indirect comparison in network meta-analysis was also concerned (48). In contrast, we updated the knowledge with 4 new trials and provided more solid evidence regarding the comparison between HIIT and MICT.
Although our results supported the superiority of HIIT over MICT in improving V̇O2-peak, the underlying mechanism remained unclear. Our meta-analysis showed that both peak and mean heart rate was higher during HIIT sessions than during MICT sessions (Figure 4). This finding may imply that the HIIT session provided higher averaged training intensity than the MICT did. Since it has been well established that the effect of aerobic training on CRF is associated with training intensity (52), a higher averaged training intensity may contribute to the superiority of HIIT. This notion should be confirmed with more evidence involving the comparison regarding the training fidelity between HIIT and MICT.
Training intensity (i.e., high or moderate) and duration (i.e., interval or continuous or time spent on a session) are two controlling factors of training volume. It is rational to compare two interventions at different intensity but with same duration, or with different duration but at same intensity. However, comparing two training modes that differ in both intensity and duration leads to methodological challenges. At least one included study controlled for training volume and still found evidence favoring HIIT. In the study by Hsu et al., the HIIT protocol consisted of alternating intervals at 40 and 80% of V̇O2-peak, while the MICT protocol was performed at a steady intensity of 60% V̇O2-peak, with a matched total training duration (36). This isoenergetic expenditure design minimized the confounding effect of training volume. We advocate for future trials to control training volume (i.e., the integral of training intensity and duration) when comparing HIIT and MICT. Doing so will provide clearer insights into the underlying factors contributing to HIIT’s potential superiority.
Ho-Wei Lin
Yuan-Chen Chang2
