Poststroke Functional Outcomes Unchanged by Addition of Inhospital Remote Ischemic Conditioning

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).

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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).

REFERENCE
1. Blauenfeldt RA, Hjort N, Valentin JB, et al. Remote ischemic conditioning for acute stroke: the RESIST randomized cinical trial. JAMA Netw Open. 2023;330(13):1236-1246. doi:10.1001/jama.2023.16893