In comparison with placebo, treatment with remote ischemic conditioning was not associated with a significant shift toward better functional outcome at 90 days.
Findings from a large-scale randomized clinical trial (NCT03481777) of patients with prehospital stroke symptoms for less than 4 hours showed that remote ischemic conditioning (RIC) initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days.1
Led by Rolf Blauenfeldt, MD, a stroke neurologist at Aarhus University, the study featured 1500 patients across 4 stroke centers in Denmark who were randomly assigned to either RIC using an inflatable cuff on 1 upper extremity (n = 749) or sham cuff pressure (n = 751). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started immediately after randomization in the ambulance or helicopter.
The trial used improvement on the modified Rankin Scale (mRS), a functional outcome, as the primary end point. Early after the trial had commenced, the primary outcome measure was changed from a 24-hour difference in Prehospital Stroke Score (PreSS) to the difference in functional outcome measured across the entire range of the mRS. For a subset of patients admitted to Aarhus University Hospital, ischemic postconditioning was continued twice daily for 8 days. Ischemic postconditioning was continued at home or a rehabilitation center if the patient had been discharged before day 7.
A total of 902 patients were included in the target population, 436 in the RIC group and 466 in the sham group. Of these, 737 patients (82%) had acute ischemic stroke and 165 (18%) had intracerebral hemorrhage. Published in JAMA Network, findings showed that RIC was not associated with a significant shift toward better functional outcome, as those in the RIC group had median mRS scores of 2 (IQR, 1-3) compared with scores of 1 (IQR, 1-3) in the sham group (OR, 0.95; 95% CI, 0.75-1.20; P = .67).
In secondary analyses of those with acute ischemic stroke, RIC treatment was not significantly associated with improvement in functional outcome among those treated with reperfusion therapies (OR, 1.08; 95% CI, 0.79-1.49; P = .63) and those who did not (OR, 0.88; 95% CI, 0.54-1.42; P = .60). Between the RIC and sham groups, there was no significant differences at 90 days in the frequency of MACCEs (13.1% vs 13.3%; HRR, 0.98; 95% CI, 0.68-1.41), recurrent ischemic events (5.7% vs 6.9%; HRR, 0.83; 95% CI, 0.49-1.39), and all-cause mortality (8.5% vs 9.9%; rate ratio [RR], 0.88; 95% CI, 0.59-1.33).
A favorable functional outcome, otherwise mRS scores between 0 and 2, were found in 67.9% (n = 296) of those in the RIC group vs 66.5% (n = 310) of those on sham. At 90 days, 7.3% and 6.7% of those in the RIC and sham groups, respectively, experienced cardiovascular mortality (RR, 1.14; 95% CI, 0.69-1.88; P = .61). Among those with a final diagnosis of stroke or transient ischemic attack, RIC was not significantly associated with remission of symptoms within 24 hours with 96 patients (18.6%) in the RIC group vs 90 patients (16.9%) in the sham group achieving complete remission (OR, 1.10; 95% CI, 0.89-1.36; P = .39).
Using the overall population of 1500 patients prior to exclusions, adverse events (AEs) were similar between the 2 observed groups. In the RIC group, 23.7% of participants (n = 169) experienced at least 1 serious AE vs 24.3% (n = 175) of those in the sham group (RR, 0.97; 95% CI, 0.85-1.11; P = .68). Between the 2 groups, upper extremity pain during treatment and/or skin petechia was more frequent in the RIC group (7.2%) than sham (1.5%). Among the entire population of 1433 patients, 41 (5.8%) of 713 in the RIC group and 47 (6.5%) of the 720 in the sham group died within 90 days (RR, 0.87; 95% CI, 0.58-1.31; P = .51).