Abstract
Introduction: There remains a lack of consensus among physicians regarding the blood pressure (BP) management strategy for acute ischemic stroke patients; this study sought to determine current practice patterns and extension of consensus among stroke physicians after publications of several randomized controlled trials (RCTs). Methods: An online survey of stroke clinicians registered to the Oriental Conference of Interventional Neurovascology (OCIN) platform and Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED2/MT) trail collaborators was conducted to investigate the BP management strategy after mechanical thrombectomy (MT). The survey was sent out in March 2024, extracted within 1 month, and then analyzed comprehensively using descriptive statistics. Results: A total of 351 available responses were collected and analyzed. These participants mostly come from tertiary-level hospitals (90.6%) in 31 provinces in China. During MT, the most popular a BP target was 140–160 mm Hg (36.5%, 128/351) and 120–140 mm Hg (26.8%, 94/351). For patients achieved successful reperfusion, those who achieved expanded treatment in cerebral infarction (eTICI) 3 were expected to maintain BP target of 120–140 mm Hg (56.7%, 199/351) or <120 mm Hg (27.1%, 95/351), while eTICI 2b were wished to 120–140 mm Hg (45.3%, 159/351) or 140–160 mm Hg (38.5%, 135/351). For patients who achieved unsuccessful reperfusion, the most selected BP target was 140–160 mm Hg (40.7%, 143/351). In brief, clinical doctors from China with different experiences have different views on the goals of BP management. Conclusions: The survey highlights inter-institutional variability among stroke experts regarding the optimal BP target for acute ischemic stroke. While a majority of institutions have established standardized protocols for post-MT BP management, further prospective randomized trials are warranted to determine the optimal BP target.
Introduction
A growing number of acute ischemic stroke (AIS) is getting treated with mechanical thrombectomy (MT) [1]. The American Heart Association and American Stroke Association (AHA/ASA) guideline recommended blood pressure (BP) target below 180/105 mm Hg during the MT and within 24 h, but the BP target after successful reperfusion is not yet determined. Clinical evidence of BP target was mostly derived from small pilot studies that observed an association between high BP with increased risk of intracranial hemorrhage and worse clinical outcomes. BP-TARGET is the first randomized controlled trial (RCT) comparing intensive and moderate BP control in AIS patients, indicating the neutral effect of intensive BP control [2]. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT) trial, which found that intensive control of systolic BP to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of acute ischemic stroke patients [3]. BEST-II provided the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg) [4]. Another randomized clinical trial-The OPTIMAL-BP also suggested that intensive BP management should be avoided after a successful EVT in AIS [5]. However, gaps between clinical practice and randomized trails evidence are not effectively resolved. Significant heterogeneity of BP management among institutions exists, which may influence clinical equipoise for MT [6]. Thereafter, there is a critical need to understand gaps between clinical practice and randomized trails evidence. This survey outlines physicians’ preferences on decisions of peri-operative BP management and identifies the disagreements among different specialties.
Methods
Study Design
An online survey was sent out to stroke experts registered to the Oriental Conference of Interventional Neurovascology (OCIN) group and DIRECT-MT trial, ENCHANTED2/MT trial, and PROTECT-MT trial collaborators [3, 7]. Approximately 2000 stroke physicians of any specialty were invited to participate in the survey, based on their experience with MT for stroke and their involvement in previous clinical trials. The online survey tool (wjx.com) was used for survey distribution, data collection, and encryption. Source data of the survey were only available to individual investigators. Incomplete responses were excluded to avoid duplicate analysis. Study data are available on reasonable request to the corresponding author and first co-author.
Data Collection
The questionnaire collected basic information and answers to some questions, primarily focused on current practice with regard to clinical practice including decisions on alteplase and MT treatment, technical preference, clinical scenarios, and BP management. In addition, it also included some specific case scenarios consisting of clinical information and imaging findings; the participants needed to choose strategies in such specific contexts to reflect real clinical decisions.
The survey was sent by an applet (wjx.com) within WeChat in March 2024, and a reminder was sent once 2 weeks later. The link was closed in 1 month, and data were extracted. All data were downloaded from the applet into Microsoft Excel for further analysis.
Statistical Analysis
Standard descriptive statistics were used for the overall analysis of response data. Depending on the distribution of data, the Student’s t test was used for continuous variables and the chi-square tests for categorical variables. p values <0.05 were considered statistically significant. Data analysis was performed in Stata 15.1. Figures were created with GraphPad version Prism.9.5.
Results
Overall, 351 respondents completed the survey during the study period. Participants were from a variety of specialties and had years of experience. The participants mostly come from teaching hospitals (78.4%, 275/351) and tertiary-level hospitals (90.6%, 318/351), distributed throughout China, including all Chinese provinces except Hong Kong, Macao, and Taiwan. The number of MT surgeries performed by the surveyed hospitals in 2023 concentrated in two ranges of 25–50 (25.9%, 91/351) and 50–100 (20.8%, 73/351), among which the number of MT surgeries participated by participants concentrated in two ranges of 10–30 (34.5%, 121/351) and 30–100 (36.2%, 127/351). The majority of the respondents are of the age group 41–50 (49%, 172/351), with nearly half (48.2%, 169/351) of them having been engaged in neurological intervention for more than 10 years, and the vast majority of them holding professional titles such as full professor (33.6%, 118/351) and associate professor (37.9%, 133/351). Most respondents are neurologists (50.7%, 178/351) or neurosurgeons (32.8%, 115/351), while the rest are neurointerventional physicians (16.5%, 58/351).
About 29.9% (105/351) of clinicians reported that the great mass of AIS thrombectomy patients have preoperative systolic blood pressure (SBP) >180 mm Hg, while 76.4% (268/351) of clinicians reported that only a small portion of patients still have postoperative SBP >180 mm Hg. For patients with SBP >180 mm Hg before thrombectomy, 38.8% (136/351) of clinicians choose to control the SBP to below 180 mm Hg. Also, 52.7% (185/351) of clinicians believe that if thrombolysis is performed, it will be reduced to below 180 mm Hg, while those who do not undergo thrombolysis will not be treated. A very small number of clinicians (7.1%, 25/351) choose not to handle it. There is no unified formal BP management plan among the clinicians. For biased BP management goals, once MT surgery begins, over one-third (36.5%, 128/351) of clinicians control SBP between 140 and 160 mm Hg, while the other one-fourth (26.8%, 94/351) choose 120–140 mm Hg (Fig. 1a). For patients who had achieved successful reperfusion which expanded treatment in cerebral infarction (eTICI) 3, more than half of the clinicians wished to maintain an SBP of 120–140 mm Hg (56.7%, 199/351), while one-fourth clinicians reported being more aggressive in aiming for an SBP of <120 mm Hg (27.1%, 95/351) (Fig. 1b). However, for patients who had achieved successful reperfusion which eTICI 2b, apart from nearly half of the clinicians wished to maintain SBP target of 120–140 mm Hg (45.3%, 159/351), more than one-third of clinicians reported being more aggressive SBP target of 140–160 mm Hg (38.5%, 135/351) (Fig. 1c). For patients who achieved unsuccessful reperfusion, clinicians favored a higher target SBP: 143 (40.7%) and 70 (19.9%) choosing SBP levels of 140–160 mm Hg and 160–180 mm Hg, respectively, with even 59 (16.8%) recommending a high level of SBP <180 mm Hg (Fig. 1d).
Tendency toward SBP management goals in different situations. The intention of SBP control target in AIS patients treated with MT during MT (a); post-MT with successful reperfusion, defined as eTICI score 3 (b); post-MT with successful reperfusion, defined as eTICI score 2b (c); post-MT with unsuccessful reperfusion (d). eTICI, expanded treatment in cerebral infarction; MT, mechanical thrombectomy; SBP, systolic blood pressure.
Tendency toward SBP management goals in different situations. The intention of SBP control target in AIS patients treated with MT during MT (a); post-MT with successful reperfusion, defined as eTICI score 3 (b); post-MT with successful reperfusion, defined as eTICI score 2b (c); post-MT with unsuccessful reperfusion (d). eTICI, expanded treatment in cerebral infarction; MT, mechanical thrombectomy; SBP, systolic blood pressure.
Figure 2 shows the different SBP targets by subgroups. The clinicians were divided into four groups based on the number of MT cases they involved in 2023, including less than 10 cases (17.7%, 62/351), 10–30 cases (34.5%, 121/351), 30–100 cases (36.2%, 127/351), and more than 100 cases (11.7%, 41/351). More experienced clinicians(more than 100 cases)are more inclined to choose SBP levels between 140 and 160 mm Hg (46.3%, 19/41) during MT, while the clinicians in less than 10 cases (33.9%, 21/62), 10–30 cases (31.4%, 38/121), 30–100 cases (39.4%, 50/127) choose this goal is lower. When eTICI 3 or eTICI 2b were not achieved, experienced clinicians are also more prefer choose to control SBP between 140 and 160 mm Hg (51.2%, 21/41). For patients who had achieved successful reperfusion which eTICI 3, more than half of the clinicians in all subgroups chose SBP levels between 120 and 140 mm Hg (Fig. 2a–d).
Tendency toward SBP management goals for different doctors. The intention of SBP control target for different doctors in AIS patients treated with MT during MT (a); post-MT with successful reperfusion, defined as eTICI score 3 (b); post-MT with successful reperfusion, defined as eTICI score 2b (c); post-MT with unsuccessful reperfusion (d). eTICI, expanded treatment in cerebral infarction; MT, mechanical thrombectomy; SBP, systolic blood pressure.
Tendency toward SBP management goals for different doctors. The intention of SBP control target for different doctors in AIS patients treated with MT during MT (a); post-MT with successful reperfusion, defined as eTICI score 3 (b); post-MT with successful reperfusion, defined as eTICI score 2b (c); post-MT with unsuccessful reperfusion (d). eTICI, expanded treatment in cerebral infarction; MT, mechanical thrombectomy; SBP, systolic blood pressure.
For the above SBP management goals, about one-fifth choose to maintain for 24 h (20.2%, 71/351) and 48 h (21.08%, 74/351), respectively, while another 31.9% (112/351) of clinical doctors choose to maintain for 72 h. For the clinical practice of BP management after thrombectomy, nearly half of all (47%, 165/351) participants received standardized treatment according to guidelines, 8.8% (31/351) received standardized treatment specified by the department, and the remaining 44.2% (155/351) chose individualized treatment. Urapidil (97.44%, 342/351) is the most commonly used intravenous antihypertensive drug, followed by nitroprusside (38.75%, 136/351) and nicardipine (34.76%, 122/351). In terms of commonly used oral antihypertensive drugs, the top three are calcium channel blockers (93.73%, 329/351), angiotensin II receptor inhibitors (77.21%, 271/351), and angiotensin-converting enzyme inhibitors (70.37%, 247/351). Urapidil (86.04%, 302/351) is widely recognized as the preferred antihypertensive drug.
Discussion
Before the intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT) began, we performed a baseline survey to realize the opinions over targets for BP control after MT in patients with acute ischemic stroke. The method was to invite doctors qualified in MT to take part in an online questionnaire about BP management. The results showed that the most popular BP target for reperfusion patients was 140–160 mm Hg (n = 47, 53%) and <120 mm Hg (n = 28, 32%) and the BP management protocols for patients with MT were not standardized in institutions across China, which clarified the necessity of performing the ENCHANTED2/MT [8]. Now, after obtaining new results and evidence from the ENCHANTED2/MT and a series of other clinical trials, we hope to investigate whether BP management strategies in Chinese hospitals have been changed and standardized through this study, and observe whether more further experiments are necessary to identify the best BP management strategies for AIS patients. In this survey, clinical doctors have different views on the goals of BP management compared to the past. Patients with eTICI 3 were wished to maintain SBP target of 120–140 mm Hg (n = 199, 56.70%) and <120 mm Hg (n = 95, 27.07%), while eTICI2b were wished to maintain 120–140 mm Hg (n = 159, 45.30%) and 140–160 mm Hg (n = 135, 38.46%). Our national online survey of stroke experts revealed a lack of consensus on the decision of optimal BP target even after the publication of four RCTs [2‒5].
As AHA/ASA guidelines recommend [9], it is reasonable to maintain BP less than 180/105 mm Hg before and after endovascular thrombectomy. In a meta-analysis based on individual patient data from seven randomized trials including MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE, high admission systolic BP was associated with worse functional outcome after stroke. However, the effect of endovascular thrombectomy is not negated by systolic BP [10]. However, whether systolic BP before thrombectomy should be controlled to an intensive or a standard target is not yet investigated in any randomized or cohort studies. Maintaining a high BP seems to be beneficial in keeping collateral flow adequate and improving clinical outcomes to date.
Post-thrombectomy BP management strategy in previous RCTs was different. The ESCAPE protocol states that SBP over 150 mm Hg is probably useful in promoting and keeping collateral flow adequate while the artery remains occluded and that controlling BP once reperfusion has been achieved and aiming for a normal BP for that individual is sensible [11]. The DAWN protocol, on the other hand, recommends maintaining SBP <140 mm Hg in the first 24 h in subjects who are reperfused after MT [12]. For better understanding of the optimal BP target, several completed and ongoing RCTs focus on the optimal BP target including BP-TARGET, ENCHANTED2/MT (2), OPTIMAL-BP, CRISIS-I, BEST-II, PRESS, DETECT, and INDIVIDUATE et al. [2‒5]. BP-TARGET trial did not find a benefit to intensive BP lowering to less than 130 mm Hg regarding the risk of symptomatic intracranial hemorrhage, but it was not sufficiently powered to detect differences in functional outcomes. Next the ENCHANTED2/MT trial, the first trial of intensive BP lowering in patients with hypertension following successful MT powered to detect a difference in functional outcomes. The trial randomized patients to either a systolic BP less than 120 or 140–180 mm Hg. The trial was terminated early due to safety concerns in the more intensive BP-lowering group. The trial showed a harm of intensive BP control after MT.
Individualized BP control after MT is influenced by several factors, of which reperfusion degree to be the most important. Reperfusion degree is commonly assessed with TICI scale and its iterations. Expanded TICI (eTICI) is commonly used to assess blood flow reperfusion after MT, and eTICI >2b is usually considered to be successful reperfusion. In a meta-analysis of 5874 patients from 7 published studies detected no interaction of reperfusion status to the associations of mean SBP with outcomes [13]. However, lower BP targets are often proposed and implemented in clinical practice only for patients who have successfully achieved reperfusion. Martins et al. [14] performed multivariate analyses of SBP and DBP in patients according to the status of reperfusion, and a linear correlation was found between SBP and DBP in patients with reperfusion and functional prognosis (SBP: OR = 1.015, p = 0.001; DBP: OR = 1.019 p = 0.012), while there was a J-shaped relationship in patients with unsuccessful reperfusion. However, the BP parameter in this study was 24-h post-stroke onset BP, which covers baseline BP, intraprocedural BP during intravenous thrombolysis or endovascular therapy, and postprocedural BP, ignoring the fact that the condition of the body’s peripheral circulation is not the same between the various phases, and that the inclusion of these BP indicators at different times in the analysis has a large impact on the results. However, we have to recognize the importance of blood flow reperfusion in BP management after mechanical thrombolysis and the need for further studies to clarify the goals of BP management in patients with successful blood flow reperfusion.
This study collected responses from physicians from 31 provinces in China, with the vast majority having high seniority and extensive experience in MT surgery. Our results accurately reflect the BP management strategies of Chinese doctors after thrombectomy in actual clinical practice.
Unfortunately, our study still has limitations. The survey is national while not international; thereafter, organizations that did not participate in the MT series of studies were not surveyed. Heterogeneity among countries should be further investigated. Second, there is no investigation into the methods of BP monitoring and the way to achieve BP lowering and control. Finally, most of the physicians come from tertiary-level hospitals, which cannot represent the level of all hospitals in China.
Conclusion
Our national online survey of stroke experts identified a lack of consensus on the optimal BP target after endovascular treatment in acute ischemic stroke patients. There is an urgent need for high-quality clinical trials to provide stronger evidence to avoid the potential harm of AIS thrombectomy patients and improve prognosis.
Acknowledgments
The authors thanks all the clinicians from hospitals at all levels, who participated in this survey, including stroke clinicians registered to OCIN platform and ENCHANTED2/MT trial collaborators.
Statement of Ethics
Ethics and regulatory entities have approved the ENCHANTED2-MT study in the participating hospitals. The first study protocol was reviewed and approved by Shanghai Changhai Hospital Ethic Committee, Approval No. CHEC2020-001. Written informed consent to participate was not directly obtained but inferred by completion of the questionnaire/participation in the interview.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
The study is supported by the Basic Experiment Funding of NMU (Grant No.: 2022QN052) and China Postdoctoral Science Foundation (Grant No.: 2023M740708).
Author Contributions
Jianmin Liu, Lili Song, Pengfei Yang, and Yang Zhao designed the ENCHANTED2/MT study. Xiaoxi Zhang and Yunke Li designed the questionnaire. Bing Zhang and Yihan Zhou analyzed data and drafted the manuscript. Yongwei Zhang provided advice on the first draft and revised the article critically for important intellectual content. All the authors reviewed the manuscript and approved the submission.
Data Availability Statement
The data that support this study can be disclosed with the permission of the ENCHANTED2/MT Steering Committee. The data that support the findings of this study are not publicly available due to privacy reasons but are available from Dr. Lili Song upon reasonable request.