In-transit Preconditioning Study Shows Neutral Effect in Stroke Patients

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Although a prehospital strategy of remote ischemic preconditioning appears safe in patients with acute stroke, magnetic resonance imaging (MRI) results suggest little difference between treated and untreated patients, according to a study published online November 7, 2013, ahead of print in Stroke.

Researchers led by Kristina Dupont Hougaard, MD, of Aarhus University Hospital (Aarhus, Denmark), randomized 443 patients with symptoms of acute stroke (transient ischemic attack, acute ischemic, or hemorrhagic) to IV recombinant tissue plasminogen activator (rtPA) with (n = 247) or without (n = 196) remote ischemic preconditioning between June 2009 and January 2011.

No Clinical Effect Seen

Compared with controls, those randomized to preconditioning had a higher incidence of TIA (17% vs. 8.2%; P = 0.006), and a lower National Institutes of Health (NIH) Stroke Scale score on admission (P = 0.016). However, after reclassification for missing data and other issues, there were no differences in demographic and clinical characteristics between the 2 groups.

At 3 months, there were no differences in penumbral salvage, final infarct size, and infarct growth on MRI between the intervention and control groups (table 1).

Table 1. MRI Results at 3 Months

However, tissue analysis to test for sensitivity to treatment-related effects showed a treatment-dependent change in infarct risk when correcting for the differences in baseline values of mean transit time and perfusion-weighted imaging. Tissue infarct risk by vessel status at arrival and after administration of rtPA showed a reduction of infarct risk in diffusion-weighted imaging-positive tissue at 1 month for patients treated with preconditioning who had no baseline occlusion. In those with persisting occlusion, there also was a reduction of infarct risk except among those with severely prolonged transit times.

Analysis of vessel status at arrival also indicated that in preconditioned patients with no vessel occlusion on admission, there was an overall reduction in the risk of infarction for tissue subjected to preconditioning.

Enough Suggestion of Benefit to Move Ahead

According to the study authors, the patient-level analysis suggests the distribution of diffusion-weighted imaging lesion intensities “seems left shifted for patients treated with [preconditioning] during transportation to the hospital, suggesting a lower degree of cytotoxic edema and therefore potentially less tissue damage when perfusion is promptly restored.” The benefits of the strategy, therefore, “may not be limited to penumbral tissue, but seems to pertain to tissue within the [diffusion-weighted imaging] lesion,” they say.

While any translation of these results into a possible clinical benefit remains unknown, Dr. Hougaard and colleagues say their study is consistent with at least 1 other that has indicated possible neuroprotective effects from remote preconditioning in the poststroke phase in patients with intraarterial stenosis.

The study is limited though by an acknowledged error in randomization. This occurred in the initial period when final consent was not obtained from patients randomized to no preconditioning and as a result those patients were not included in the analysis. “This imbalance may have affected the clinical outcome data but does not affect the tissue-level results in that this approach is inherently adjusted for any imbalance in baseline [perfusion-weighted imaging] and [diffusion-weighted imaging],” they write.

Study Details

Remote preconditioning was performed by ambulance staff during transportation and consisted of 4 inflations of a standard upper limb blood pressure cuff to either 200 or 25 mm Hg above the systolic blood pressure, each lasting 5 minutes and separated by 5 minutes of cuff deflation. Preconditioning also was performed approximately 1 hour before MRI in those patients who participated in the MRI portion of the study. Symptom severity was not assessed prior to preconditioning.

Source:

Hougaard KD, Hjort N, Zeidler D, et al. Remote ischemic preconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: A randomized trial. Stroke. 2013;Epub ahead of print.

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