"The results of that trial actually came out the opposite to what we hypothesized, and that is that intensive early training later reduced odds of an unfavorable outcome after stroke at three months," Julie Bernhardt, PhD, from the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia, reported.
Speaking here at the World Stroke Congress (WSC) 2016, she said the overall mortality rate at day 14 was low at 3.8%, but intensive therapy early after a stroke was a risk factor. The message was not to withhold all therapy but rather that conventional post-stroke therapy appeared better than intensive therapy.
A Very Early Rehabilitation Trial (AVERT) was a pragmatic, real-world, randomized, controlled study testing frequent, higher-dose, very early (less than 24 hours) out-of-bed mobilization (VEM) after a stroke compared with usual post-stroke care. The goal was to improve independent survival at 3 months, as shown by a modified Rankin Scale score of 0 to 2.
Previously published results in The Lancet showed a 27% risk for worse outcome with VEM vs usual care (adjusted odds ratio [OR], 0.73; 95% confidence interval [CI], 0.59 - 0.90; P = .004). A prespecified tertiary analysis, presented here, assessed safety and serious adverse effects (SAEs) as adjudicated by a blinded outcome panel.
Deaths and SAEs were classified as stroke related (progression or new stroke) or related to immobility (eg, pulmonary embolism, deep-vein thrombosis, urinary tract infection, pressure sores, pneumonia, or falls).
Among the study inclusion criteria were a first or recurrent ischemic or hemorrhagic stroke within 24 hours of symptom onset, age 18 years or older, physiologic parameters within certain limits, being rousable to voice, with thrombolytic therapy permitted.
Patients (n = 2104) were randomly assigned equally to usual care until discharge or for a maximum of 14 days or to VEM plus usual care. VEM consisted of a first physical therapy intervention at less than 24 hours after stroke and at least three out-of-bed sessions per day, 6 days per week through day 14.
Patients in the VEM group were 76% more likely to die by day 14 compared with those in the usual care group. Among 1048 VEM recipients, 48 died (4.6%), vs 32 (3.0%) of 1050 usual care recipients (OR, 1.76; 95% CI, 1.06 - 2.92; P = .029).
The most prevalent causes of death were stroke progression, with 28 deaths in the VEM group vs 16 in the usual care group, and pneumonia, which caused 10 and 8 deaths, respectively.
For the 3.8% of patients who died, older age, more severe strokes as assessed by the National Institutes of Health Stroke Scale, ischemic heart disease, smoking, atrial fibrillation, and stroke type were all significant risks for death. However, receiving thrombolysis or not was not a risk factor.
A subgroup analysis showed no significant differences favoring VEM or usual care according to age, stroke severity or type, use of thrombolysis, time to first mobilization, or geographic region of participant recruitment.
Nonfatal SAEs did not differ between the treatment groups, whether neurologic, immobility related, or from falls. About 90% of patients in each group had no SAE, even though 25% of patients were 80 years or older and 45% of patients had moderate to severe strokes.
Session moderator Peter Sandercock, MA, DM, chairman of medical neurology at the University of Edinburgh, United Kingdom, told Medscape Medical News that he considers AVERT "one of the most interesting trials, for two reasons."
The first is the methodology, which tested "two different forms of rehabilitation in early stroke" in a large, randomized, multicenter trial, "and that in itself is a landmark achievement, getting to the end of the trial with high data quality."
He explained that usual care is already fairly active, and one needs to be cautious about intensive intervention in severe strokes.
"What needs to be done now is to explore the dose intensity of rehabilitation," he recommended. And he emphasized that the results do not say that early rehabilitation should not be quite intensive, but "it shouldn't be super intensive, and we need to think a little bit more of how to target it."
Professor Sandercock said populations in the Western world are aging, and the prevalence of strokes and comorbidities is projected to greatly rise, so this study is an enlightening first step about how to think about risk factors and rehabilitative interventions.
There was no commercial funding of the study. Professor Bernhardt and Professor Sandercock have disclosed no relevant financial relationships.
World Stroke Congress (WSC) 2016. Presented October 27, 2016.