Effect of Remote Ischemic Conditioning on Outcomes for Acute Ischemic Stroke Patients Undergoing Alteplase Intravenous Thrombolysis: A Systematic Review and Meta-Analysis With Trial Sequential Analysis

Remote ischemic conditioning (RIC) is a simple, noninvasive intervention hypothesized to reduce ischemia-reperfusion injury in acute ischemic stroke (AIS). Its role as an adjunct to intravenous thrombolysis (IVT) remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials assessing RIC in AIS patients treated exclusively with IVT. Major databases were searched through February 2025 (PROSPERO: CRD420251144277). The risk of bias was evaluated using the Cochrane tool, and evidence certainty was assessed with Grading of Recommendations Assessment, Development, and Evaluation. Trial sequential analysis was also performed. Six randomized controlled trials (n = 955; RIC = 502, control = 453) met eligibility. Safety outcomes were comparable between groups, with no significant differences in stroke recurrence [risk ratio (RR) = 0.97; 95% confidence interval (CI), 0.63-1.48], hemorrhagic transformation (RR = 1.24; 95% CI, 0.67-2.31), or 90-day mortality (RR = 1.19; 95% CI, 0.46-3.07). RIC did not significantly improve excellent functional outcome (modified Rankin Scale 0-1 at 90 days: RR = 1.07; 95% CI, 0.95-1.20) or functional independence (modified Rankin Scale 0-2: RR = 1.03; 95% CI, 0.89-1.03). Barthel Index scores showed a nonsignificant trend toward benefit (mean difference = 2.77; 95% CI, -1.51-7.06), and National Institutes of Health Stroke scores at 24 hours, 7 days, 30 days, and follow-up were unchanged. Trial sequential analysis showed the required information size was not reached, and the Grading of Recommendations Assessment, Development, and Evaluation certainty was low to very low. RIC is safe but has not yet been shown to significantly improve functional or neurological outcomes in AIS patients treated with IVT. Future trials should assess RIC in patients receiving different types of thrombolysis (alteplase vs tenecteplase).