According to previous studies, increased systolic blood pressure (SBP) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) has been correlated with worse clinical outcomes and an increased risk of intracranial hemorrhage (ICH) (1–7). The most recent guidelines, however, recommended a decent blood pressure target to be <180/105 mmHg in the first 24 h after endovascular treatment (8, 9). According to the second randomized controlled enhanced control of hypertension and thrombectomy stroke study (ENCHANTED-2/MT) (10), after successful reperfusion in patients with AIS, which was considered complex due to various factors, including heterogeneity in age, cause of stroke, occlusion location, and collateral status, an intensive blood pressure (BP) control of <120 mmHg was deemed harmful (11–14). An aggressive approach to lowering the BP can lead to neurological worsening in patients with incomplete reperfusion, for instance, 2b-or 2c-grade expanded thrombolysis in cerebral ischemia (eTICI) with the area that has not been reperfused. The blood pressure target in acute stroke to reduce hemorrhage after endovascular therapy trial showed a comparable effect of intensive BP control (<130 mmHg) over the standard group (130–185 mmHg) on the clinical outcome or radiological intraparenchymal hemorrhage (15). The transient focal disruption of cerebral autoregulation renders perfusion of the ischemic tissue directly dependent on systemic BP (16). Further investigation is required to determine if the harmful effect of intensive BP control is universally similar in patients with different reperfusion statuses after EVT. We investigated the association between post-mechanical thrombectomy (MT) BP level and reperfusion status in patients with stroke to explore any harmful, comparable, or beneficial effects of the intensive BP control.

During the study period, 428 patients with LVO were treated with MT (Figure 1). The enrolled study population consisted of 263 patients (mean age = 68 ± 11 years, 63.1% men, median NIHSS score = 16 points [IQR = 9–22], and median ASPECTS score = 9 points [IQR = 7–10]) who were treated with MT and achieved reperfusion (eTICI ≥2b). Complete reperfusion (eTICI = 3) was achieved in 210 patients (79.8%) and incomplete reperfusion (eTICI = 2b or 2c) in 53 patients (20.2%). The baseline characteristics of the study population are presented in Table 1. In the complete reperfusion group, 64 (30.5%) patients had atrial fibrillation, 50 (23.8%) patients were treated for intravenous thrombolysis, and 101 (48.1%) patients were due to arteriosclerotic disease. Furthermore, 65 (31.0%) patients had internal carotid artery (ICA) occlusion, 105 (48.1%) patients had middle cerebral artery or anterior cerebral artery occlusion, 16 (7.6%) patients had vertebral artery occlusion, and 24 (11.4%) patients had basilar artery occlusion. In the incomplete reperfusion group, 25 (47.2%) patients had atrial fibrillation, 9 (17.0%) patients were treated for intravenous thrombolysis, and 21 (39.6%) patients were due to arteriosclerotic disease. Furthermore, 26 (49.1%) patients had ICA occlusion, 23 (43.4%) patients had middle cerebral artery or anterior cerebral artery occlusion, and 4 (7.5%) patients had vertebral artery occlusion. The proportion of patients with cardioembolic stroke was significantly higher in the incomplete reperfusion group than in the complete reperfusion group (p = 0.011), which was similar to the proportion of patients with ICA occlusion (49.1% and 31.0% in the incomplete and complete reperfusion group, respectively). The risk of sICH in the complete reperfusion group (5.8%) was similar, without any statistically significant difference, to that in the incomplete reperfusion group (5.7%) (p = 1.000). Similarly, END occurred in 13.8 and 18.9% of patients in the two groups, with no statistical significance (p = 0.586). However, the risk of aICH was significantly higher in the incomplete reperfusion group (15.5%) than in the complete reperfusion group (28.3%) (p = 0.031). The proportion of patients with 3-month functional independence tend to be higher in the complete reperfusion group (50.5%) than in the incomplete reperfusion group (36.7%). Nevertheless, the proportion of patients with 3-month mortality tend to be lower in the complete reperfusion group (19.1%) than in the incomplete reperfusion group (24.5%).

The comparison of the baseline characteristics and outcomes in the two groups of post-MT maximum SBP among patients with successful reperfusion after EVT is presented in Table 2. Although the baseline characteristics of the two groups did not differ, their clinical outcomes were notably different. Both groups documented similar SBP and diastolic BP (DBP) at admission (SBP: 150.6 ± 28.9 mmHg versus 154.0 ± 28.9 mmHg, p = 0.381; DBP: 86.7 ± 18.3 mmHg versus 85.1 ± 16.7 mmHg, p = 0.489). In patients with a maximum SBP of >160 mmHg, the risk of sICH significantly increased (9.7% versus 2.7%, p = 0.029). The risk of aICH was similar (17.7% versus 18.5%, p = 1.000). END observation in both groups was comparable in patients with a maximum SBP of >160 mmHg (18.1% versus 12.2%, p = 0.222). However, in-hospital and 3-month mortality rates were significantly higher (19.0% versus 6.9%, p = 0.004, 27.4% versus 14.3%, p = 0.012, respectively). The 3-month functional independence was significantly higher in patients with a maximum SBP of <160 mmHg (38.1% versus 55.7%, p = 0.006).

The multivariable analysis and associations of different post-MT SBP averages with 3-month functional dependence after adjustment for potential confounders in the subgroup of patients with LVO with complete and incomplete reperfusion following MT are presented in Table 3. Interestingly, no association was found between postprocedural average SBP levels and risk of 3-month functional dependence, END, sICH, in-hospital mortality, and 3-month mortality (p > 0.05) (Table 3; Supplementary Table S2). Moreover, patients with an average SBP of 100–120 mmHg tended to have the best 3-month functional outcome in the complete reperfusion group, and those in the incomplete reperfusion group had worse outcomes; however, the difference was statistically insignificant. In the complete reperfusion group, the OR of the 3-month functional outcome of patients with 120–140 mmHg over those with 100–120 mmHg was 1.77 (95% CI, 0.97–3.23, p = 0.061). Additionally, no linear relationship was found between post-MT SBP and clinical outcomes based on the reperfusion status (p > 0.05) (Supplementary Table S1).

This study indicated that a maximum SBP level of >160 mmHg during the first post-MT 72 h is related to a higher likelihood of worse clinical outcomes, including in-hospital mortality, END, 3-month mortality, and 3-month functional dependence. Multivariate regression analysis did not reveal any relationship between the reperfusion status and BP level on the clinical outcomes. Additionally, patients with complete reperfusion tended to have the best functional outcome with an average SBP of 100–120 mmHg. The main finding of this study is that the association between the post-MT BP target and clinical outcome is comparable with the previous studies (18–21).

ENCHANTED-2/MT is a multicenter, open-label, blinded-endpoint, randomized controlled trial that compares the safety and efficacy of more intensive BP lowering treatment (<120 mmHg) with less intensive treatment targets (140–180 mmHg) in patients with increased BP after reperfusion with EVT (10). The likelihood of poor functional outcome was greater in the more intensive treatment group (cOR = 1.37 [95% CI: 1.07–1.76]) and increased numbers of END (cOR = 1.53 [95% CI, 1.18–1.97]) and major disability at 90 d (OR = 2.07 [95% CI, 1.47–2.93]), but no significant differences in symptomatic intracerebral hemorrhage were observed (10). Furthermore, the study found worse outcomes in the intensive group similar to that of incomplete reperfusion, for instance, eTICI 2b, an aggressive approach to lowering the BP could lead to neurological worsening, particularly in the incompletely reperfused area. We hypothesized that the reperfusion status was related to the microcirculation of the local brain tissue, and the good microcirculation may tolerate the lower blood pressure. We will further carry out relevant animal experiments to prove our conjecture.

The AURORA meta-analysis of thrombectomy for anterior circulation stroke >6 h after the last known well revealed that the post-MT functional independence was 45.9%, with a mortality rate of 16.5% and an sICH rate of 5.3% (22). Herein, the rates of functional independence, mortality, and sICH of patients with complete and incomplete reperfusion were 50.5%, 19.1% and 5.8%, 36.7%, and 24.5% and 5.7%, respectively, which were comparative to the results of the abovementioned study. Attempts to achieve an eTICI score of 3 with complete reperfusion might be the priority in performing EVT; however, considering that >half of the patients still had a residual disability at 3 months despite successful reperfusion, it is important to consider potential factors, including BP, anesthesia, blood glucose, and body temperature, that might help improve the functional outcomes. ENCHANTED-2/MT was the first randomized controlled trial that indicated that a more-intensive BP control might be harmful compared with that of <120 mmHg in patients with LVO that achieved successful reperfusion (10). An alternative interpretation is that the patients with residual unreperfused areas might have deteriorated outcomes after intensive BP control. More recently, the OPTIMAL-BP trial was terminated earlier due to safety concern and found intensive BP management (<140 mmHg) for 24 h led to a lower likelihood of functional independence at 3 months compared with conventional BP management (140–180 mmHg) (23). Interestingly, we did not find any significant relationship between post-MT BP and the reperfusion status, suggesting that further investigations were warranted for more conclusive information.

In a study, considerable discrepancy regarding BP target was reported among different institutions and physicians (24). An online survey of neurointerventionalists, neurointensivisits, and neurologists from different comprehensive stroke centers revealed that the BP target was determined by a team of physicians in a collaborative fashion (n = 30, 52%) and individualized on a case-by-case basis (n = 39, 67%) in most institutions. Among them, 36% of physicians preferred an SBP target in the 120–139 mmHg range and 5% preferred that of <120 mmHg. In another online survey endorsed by the European Society of Intensive Care Medicine (24), 54% of participants chose a BP target of <160/90 mmHg. Most participants believed that an eTICI 2b/c versus eTICI 3 reperfusion status would not affect the optimal management of post-MT SBP.

There are some limitations of this study. Because of the retrospective nature of this study, it was subjected to the biases inherent to this type of analysis. The BP levels were decided according to the preference of the physician, and not based on randomization. Furthermore, we could not evaluate the hypothesis that if BP target affected clinical prognosis, considering the information regarding the type of BP target was not adequate in the study cohort. Moreover, we did not measure the final infarct volume; therefore, we could not evaluate its association with BP level. Instead, END, which partially indicates the deterioration of cerebral infarction, was evaluated. There is also a higher proportion of patients with cardioembolic stroke in the incomplete reperfusion group, which may lead to bias. According to previous immunohistochemical staining study, platelet-rich thrombi were associated with a smaller prevalence of TICI 3 compared to platelet-poor thrombi, which is in coincidence with our result (25). Finally, the observational study design did not allow us to establish a cause–effect relationship between post-MT BP levels and functional independence in patients with LVO.

Our study showed the preliminary data indicating that SBP of >160 mmHg, following MT, was associated with an increased likelihood of 3-month mortality and functional dependence in patients with LVO. An average SBP between 100–120 mmHg tended to have a better 3-month functional independence in patients with complete reperfusion, whereas patients with incomplete reperfusion showed worse 3-month functional independence. Further investigation is needed to determine if an incomplete reperfused area can affect the BP target.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants or patients/participants legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

HX, HL and PZ: drafted this manuscript. YG, HaL, HS, WH, LZ, ZL, YZ, PX, and JL: contributed in statistical analysis, data collection, and imaging analysis. XZ and PY: designed this study. All authors contributed to the article and approved the submitted version.