Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.
“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” lead investigator Raul G. Nogueira, MD, told theheart.org | Medscape Cardiology.
“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Nogueira said.
However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age) which Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.
Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, Pittsburgh, Pennsylvania, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre, Porto Alegre, Brazil, presented the RESILIENT-Extend results at the International Stroke Conference 2024, being held this week in Phoenix, Arizona.
Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.
“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”
The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first world countries.
“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first world recruited into most other thrombectomy trials,” Nogueira noted.
The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.
They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.
These patients were identified exclusively using non-contrast CT and CT angiography imaging.
The median age of patients included was 62-63 years. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.
The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.
The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
Conflicting Results on Shift Analysis
The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.
This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).
“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Nogueira reported.
The researchers therefore used the secondary outcomes as the main results of the study.
These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs 14%, adjusted odds ratio, 2.56; P = .012).
The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.
But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).
The odds ratio for an mRS of 0-4 vs 5-6 was 0.71, and for an mRS of 0-5 vs 6, the odds ratio was 0.58. Both these results were nonsignificant.
Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.
“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Nogueira noted.
A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.
“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Nogueira commented.
Frailty: A Ceiling Effect?
He said these results from the two RESILIENT trials give a word of caution to the thrombectomy field.
“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Nogueira commented. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.”
“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients (over 68-70) years of age in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”
Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.
“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
Commenting on the RESILIENT-Extend study for theheart.org | Medscape Cardiology, Michael Hill, MD, professor of neurology at the University of Calgary, Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.
“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”
Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.
Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center-Case Western Reserve University in Cleveland, Ohio, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”
He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.
The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
Source link : https://www.medscape.com/viewarticle/expanded-window-stroke-thrombectomy-simpler-imaging-2024a10002w4?src=rss
Publish date : 2024-02-09 09:57:10
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