Discussion
death, pneumonia, stroke, hypoperfusion, infections, ischemic stroke, Pneumonia, neurological deterioration, artery atherosclerosis, infarct
PNEUMONIA, STROKE, HYPOPERFUSION, INFECTIONS, ISCHEMIC STROKE, SECONDARY, PNEUMONIA, EVENTS, ACUTE STROKE, INFARCT
In this investigator-initiated, randomized, multicenter trial, we investigated the effect of HDP (−20°) on functional outcomes in acute moderate ischemic stroke patients with probable LAA. We found that treatment with HDP for 2 weeks, applied as an adjunct to guideline-based medical management, was safe and did not improve the primary outcome (mRS 0–2 at 90 days), when compared with guideline-based medical management alone. However, HDP may have an improved effect on major secondary outcomes, including excellent functional outcome (mRS 0–1), ordinal shift distribution of mRS at 90 days, END, and change in NIHSS.Many studies have investigated the effect of head position on cerebral blood flow and cerebral perfusionThere are several differences between the current study and prior studies. First, the head position at −20° was adopted in the current study, while a horizontal supine versus sitting position was utilized in prior studiesThird, we implemented different head position interventions over time: 15 h duration within 24 h of presentation, followed by three times daily for 2 weeks in the current study, while only the first 24 h after randomization were implemented in the HeadPoST study. We postulate that longer-term HDP intervention may result in more benefits of improved cerebral perfusion, given that there may be the presence of long-lasting penumbra in this populationFor secondary outcomes, we found a significant mRS improvement at 90 days in the HDP group vs the control group, as well as improvement in NIHSS from baseline to day 12. We also observed a significant improvement in the proportion of mRS scores 0–1 at 90 days in the HDP group. For safety outcomes, there was no difference in mortality between the two groups, and no END in the HDP group. Collectively, these results support the safety and potentially improved neurological outcomes with HDP in patients with acute moderate ischemic stroke with LAA in a Chinese population.In our study, other safety endpoints, including pneumonia and cardiovascular events, were similar between the two groups. Pneumonia is a major risk factor for death after acute stroke. Preventive administration of antibiotics is superior in reducing infections after severe ischemic strokeThe strength of this study is the randomized multicenter design to determine the safety and possible efficacy of HDP in acute moderate ischemic stroke patients with probable LAA etiology. These promising results may promote further trials to investigate the effect of HDP in a broader array of AIS patients, for example, patients who develop early neurological deterioration due to hypoperfusion mechanisms, in addition to the current patients. We acknowledge several limitations to our study. The main limitation is the relatively small sample due to the pilot nature, which makes the conclusion exploratory and subgroup analysis, such as the effect of site on primary outcome, impossible. Second, the open-label design may have resulted in bias, although we used blinded evaluation at 90 days to mitigate this potential bias. Third, the highly selected population, for example, excluding patients who received thrombolysis or thrombectomy, limited to anterior circulation stroke, introduce selection bias and may limit the generalizability of our results. Fourth, the neuroimaging infarct or penumbra size was not determined in detail in the pilot study. Finally, there was no limit of head position in the control group in this trial, but we did not record the actual head position in the control group during the trial, especially within 24 h after randomization. This detailed information would be important to understand the effect of different head positions on stroke outcomes.In conclusion, this randomized clinical trial suggests that in patients with acute moderate ischemic stroke with large artery atherosclerosis, the head-down position seems safe and feasible, but does not improve 90-day favorable functional outcome as a primary outcome, although a direction of benefit was present with the potential to improve secondary outcomes. A prospective, large-sample, multicenter trial is warranted to confirm these findings.