„A new Brazilian study has shown that thrombectomy in general is beneficial for patients from a low-income population group, who present with a large vessel occlusion stroke in a later time window and can be identified as suitable for treatment without the need for advanced and costly imaging. The RESILIENT-Extend study is the first large study of thrombectomy in the late time window (8-24 hours) conducted outside of first-world countries and shows that the procedure also has benefits in a population with lower socioeconomic status without the need for expensive imaging devices,“ said lead investigator Raul G. Nogueira, MD.
The study expands the treatment window for thrombectomy worldwide with simplified selection criteria based on contrast-free CT and may potentially alter current guidelines,“ said Nogueira
However, there were some caveats to consider; particularly the lack of benefit of thrombectomy in older patients (over 68 years), which Nogueira attributed to the specific population involved in this study. He suggested that the higher age in this low socioeconomic status population may be a proxy for frailty, and the study may have identified frailty as a factor correlated with reduced or no benefit of thrombectomy.
The RESILIENT-Extend study was conducted in the public health system in Brazil and included a different population group than other thrombectomy studies predominantly conducted in first-world countries. Nogueira mentioned that the public health system in Brazil is not well-equipped and tends to care for patients at a lower socioeconomic level, which differs fundamentally from average patients in first-world countries recruited for most other thrombectomy studies.
The study involved 245 patients who experienced a stroke with large vessel occlusion within 8-24 hours of last known well. Included were patients who showed a discrepancy between clinical severity assessed by NIHSS score (National Institutes of Health Stroke Scale) and stroke burden measured by imaging ASPECTS scores. They had to have relatively high NIHSS values (8 or higher) indicating more severe strokes, but also a high ASPECTS value (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale adjusting for age to avoid inclusion of older patients with large strokes.
These patients were identified exclusively using contrast-free CT and CT angiography imaging.
The average age of the included patients was 62-63 years. Nogueira pointed out that the patients were slightly younger than in other thrombectomy studies, possibly due to strokes occurring at a younger age in low to middle-income countries, and they also have a higher mortality rate.
The mean baseline NIHSS score was 16 and the mean ASPECTS score was 7-8. The mean time to treatment was 12.5 hours, comparable to other late-window thrombectomy studies.
Contradictory results on the shift analysis
The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.
This showed a bidirectional outcome, wherein thrombectomy increased the odds of a good or excellent (mRS, 0-3) result, but there was also a non-significant increased risk of a poor outcome (mRS, 5-6).
These bidirectional findings prevented the calculation of a common odds ratio, thus the primary endpoint was not applicable,“ reported Nogueira.
Hence, the researchers used secondary endpoints as the main outcomes of the study.
These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased by thrombectomy (25% vs. 14%, adjusted odds ratio 2.56; P = .012). The number of patients achieving an excellent outcome (mRS, 0-1) also increased significantly.
However, this increase in good outcomes came at the cost of an increased risk of severe disability or death in some patients (mRS, 5-6). The odds ratio for mRS 0-4 vs. 5-6 was 0.71 and for mRS 0-5 vs. 6, the odds ratio was 0.58. Both outcomes were not significant.
Another anomaly in the RESILIENT-Extend study was the observation that there was no benefit of thrombectomy in older patients. „In general, thrombectomy studies in the first world have shown a greater treatment effect in older patients, but this was not observed in our study, where older patients (over 68 years) could not benefit from the procedure,“ noted Nogueira.
Similar observations were also made in the initial RESILIENT study in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suspicion that it is related to the population included.
„In the Brazilian public health system, older patients are very vulnerable and frail. They differ from older patients in first-world countries. It seems that they may be too frail to withstand the thrombectomy process,“ remarked Nogueira.
Frailty: A ceiling effect?
He said that these results from the two RESILIENT studies in the area of thrombectomy caution us to be careful. „Initially, it was thought that this procedure was only suitable for patients with small core infarcts, but we now have a series of studies showing the benefit of thrombectomy in large core infarcts as well,“ commented Nogueira. „We have started to believe that this intervention will benefit almost all patients with stroke due to large vessel occlusions worldwide, but our data suggest that we need to consider the specific population groups we serve, and factors such as socioeconomic status and frailty come into play.“
„Both RESILIENT studies have shown that thrombectomy does not seem to be suitable for older patients (over 68-70 years) in the public health system in Brazil,“ he noted. „In this population group, a 70-year-old patient can be very different to a same-aged patient in a first world country. I think in our population, an age over 68-70 years is a proxy for frailty, which may not be the case in first-world countries. In that sense, I think we have observed a ceiling effect in favor of thrombectomy, signifying frailty.“
Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by frailty in some patients. „The results may show that thrombectomy is beneficial for the majority of the population, but for some patients, possibly the frailest, the intervention may be overwhelming. However, suspicion of harm was not significant, so this observation may have been just due to chance,“ he added.
Comment 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% in the mRS outcome of 0-2, but a similar signal for harm, with an increase of 10.2% in mortality in the thrombectomy group, although this was not statistically significant. „This signal of harm does not appear to be due to an increase in intracranial hemorrhages or procedural mishap,“ he said. „It’s unclear why there were more deaths; the overall number of events is so low that it could be a chance finding.“
Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% lower than in the DAWN study of thrombectomy in the extended window. „This shows us that the patients selected for inclusion in RESILIENT-Extend differed physiologically from those in DAWN,“ he said.
Amrou Sarraj, MD, Professor of Neurology at the University Hospitals Cleveland Medical Center-Case Western Reserve University in Cleveland, Ohio, also commented on the study, stating, „One should congratulate the RESILIENT-Extend researchers for successfully conducting the study and providing evidence for the benefit of a thrombectomy procedure with a simplified neuroimaging protocol using CT and CTA in resource-limited settings. These results will help expand access to thrombectomy in areas where advanced imaging is not available.“