Discussion
In the current study, three main findings were as follows: (1) significant SBPr after EVT was related to the worse 90-day functional outcome in patients who achieved successful recanalisation, and there was a J-shaped relationship between SBPr and the 90-day outcome; (2) there is a negative relationship between SBPr and the incidence of sICH in patients with EVT and (3) baseline ASPECT score was an important interact factor in the relationship between outcomes after EVT and SBPr.
In theory, persistently elevated BP after successful EVT may have worse clinical outcomes by increasing the risk of cerebral oedema and intracerebral haemorrhage. Moreover, previous retrospective studies showed that SBPr in the first 24 hours after successful EVT was inversely associated with poor outcomes.16 21 However, recent RCTs have reached the opposite conclusion, which was that intensive BP management was associated with poorer functional outcomes than conventional BP management.13–15 An important issue was how the magnitude of BP reduction determined high or low risk of harms was unclear. In this study, we found that a large magnitude of SBPr after EVT was related to a poorer functional outcome at 90 days in patients who achieved successful recanalisation, and this relationship was J-shaped. Nevertheless, these results seem to contradict that of the Blood Pressure Management After Endovascular Therapy for Acute Ischaemic Stroke (BEST-II) trial and previous observational studies.16 22 23 The BEST-II trial was a phase II study to evaluate the futility of lower SBP targets after EVT (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg).23 However, this study did not show that lower SBP targets of less than 140 mm Hg and less than 160 mm Hg meet prespecified criteria for futility compared with a target of 180 mm Hg or less.
Several reasons could explain the above conflicting results. First, the intensive BP management in the previous RCTs did not consider baseline BP. In our study, the SBPr is an interesting clinical parameter that taken into account the patient’s baseline BP and attempts to reduce the intragroup variability of patients with widely varied baseline BP. Second, the selection of different baseline BPs also affects the magnitude of BP reduction. In the post hoc analysis of the BP-TARGET trial,22 the baseline BP was the end of procedure BP. Both intraoperative procedures and anaesthesia can affect the postoperative BP.24 In this study, the cath lab BP before EVT was used as the baseline BP. No patients underwent sedation or anaesthesia before the first baseline BP measurement. Third, the relationship between BP and prognosis in acute ischaemic stroke is complex. In the study, we found a J-shaped relationship between SBPr and the 90-day outcome (figure 2), which may explain that elevated SBP after successful reperfusion by EVT was harmful in most previous retrospective studies.8–10 Last, the different study designs and the imbalanced patients’ baseline characteristics likely contributed to the differences in the results.
The mechanism by which BP reduction leads to adverse outcomes may be that a significant BP lowering might further reduce blood flow to the oligemic zone and exacerbate ischaemic injury.25 Despite successful reperfusion after EVT, patients might exhibit persistent venous postcapillary thrombosis, a phenomenon also known as no-reflow.26 In this situation, the prognosis of the acute ischaemic lesion may be affected negatively by the intensive BP reduction even after successful EVT. Further analysis of the perfusion imaging data or using short-term imaging endpoints in the future may provide evidence for a potential mechanism leading to worse outcomes associated with BP reductions. It is worth noting that there is a significant dose–response relationship between SBPr and the 90-day outcome (figure 2). These results may contribute to the design of future research.
The negative association between SBPr and the incidence of sICH has been proven in previous studies.21 22 Similarly, we also found that SBPr>20% was correlated with reduced odds of sICH. In the BP-TARGET trial,13 an intensive SBP target of 100–129 mm Hg following successful EVT did not reduce the rates of radiographic ICH. A possible explanation was that the BP reduction was only 17% in the intensive SBP target group. Additionally, an important finding in our study was that the relationship between SBPr and sICH was mainly in patients with poor collateral circulation, which explained why, in the ENCHANTED2/MT trial, more intensive BP treatment did not decrease the incidence of sICH.14 In the ENCHANTED2/MT trial, the two groups all had a small core infarction and a large mismatch of perfusion deficits before EVT, which is a representative of good collateral circulation.14 It is worth noting that the decrease in sICH caused by SBPr cannot offset the adverse prognosis brought about by SBPr. Therefore, it is particularly important to continue exploring the impact of BP changes on the perioperative pathophysiological mechanisms of EVT in acute ischaemic stroke.
Another important finding was that the association of SBPr with the 90-day outcome showed a significant interaction with the baseline ASPECT score. Recently, patients with large core infarction have been confirmed to be effective with EVT by increasing evidence.3 4 The results of our study, however, did not find a correlation in these patients between SBPr and poor outcomes. Furthermore, according to the OR value, moderate BP reduction might have partial protective effects. Unfortunately, because of our small sample, the association was not statistically significant. Further trials targeting patients with large core infarctions may elucidate the role of moderate BP reduction.
To prevent reperfusion injury, antihypertensive treatment is very common in clinical practice after EVT. A recent study from South Korea shows that a medication-induced BP decrease during the first 24 hours after successful EVT may be harmful for patients with acute ischaemic stroke.27 Additionally, a subgroup analysis of the OPTIMAL-BP trial13 showed that in the conventional management group, the lower the mean 24-hour BP was, the better the outcome. Unexpectedly, in our study, the association between SBPr and poor outcomes was also found in the no-antihypertensive treatment group (spontaneous BP decreases). However, in the no-antihypertensive treatment group, we found that the relationship is only shown in populations with significant SBP drop (>30%). Moreover, a sensitive analysis for with or without antihypertensive treatment showed the similar results (online supplemental figure S1). Further research needs to be guaranteed.
The results of our study emphasise the complexity of managing BP after EVT. The main strength of this study was that it provides in-depth research on the impact of BP reduction on the prognosis after EVT. Furthermore, the subgroup analysis provides new insights for individualised BP management in patients with EVT. Nevertheless, several limitations need to be acknowledged in the study. First, due to inherent limitation of the retrospective design, the BP management protocols between different centres have not been uniformly formulated, and the emergency room antihypertensive treatment data was not obtained. However, we included the use of continuous intravenous antihypertensive treatment after EVT as an independent variable in the statistical analysis and further conducted a subgroup analysis. Second, we did not obtain detailed information on BP variability and intraoperative BP during the perioperative period of EVT, which have also been proven to be associated with functional outcomes after EVT. Third, we could not obtain the infarct volume to assess the relation between BP reduction and infarct extension, which could provide a potential mechanism leading to worse outcomes associated with BP reductions.
