Nghiên cứu điều trị lấy huyết khối cơ học bằng solitaire sau dùng tiêu sợi huyết tĩnh mạch trên bệnh nhân nhồi máu não cấp ttta

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN THANH LONG STUDY OF MECHANICAL THROMBECTOMY WITH SOLITAIRE AFTER INTRAVENOUS THROMBOLYSIS IN PATIENTS WITH ACUTE ISCHEMIC STROKE Speciality: Neuroscience Code: 9720158 ABSTRACT OF MEDICAL PH.D THESIS Hanoi – 2023 THE THESIS WAS DONE AT: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: Assoc Prof Ph.D Duong Dinh Chinh Ph.D Ngo Tien Tuan Reviewer: This thesis will be presented at Institute Council at 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year 2023 The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences INTRODUCTION Stroke is a topic of current interest due to its burdens, and Southeast Asia, which includes Vietnam, has the third highest incidence in the world LVO may account for up to 46% of acute ischemic stroke cases and with a higher risk of mortality and disability The necessary treatment for acute ischemic stroke during the acute phase is revascularization to prevent the brain from irreversible damage, with IVT using tPA as the standard treatment Besides, MT has been proven to achieve high revascularization rates and expansion of the treatment window The stentriever Solitaire is one of the most widely used devices when performing MT for ischemic stroke due to LVO The use of IVT before MT (bridging therapy) for candidates for both IVT and MT may induce complications and risks, but there is also evidence that bridging therapy has better outcomes To evaluate the results of applying this strategy in clinical practice, we conducted a "Study of mechanical thrombectomy with Solitaire after intravenous thrombolysis in patients with acute ischemic stroke" with the following objectives: To describe several essential clinical and subclinical features in patients with acute ischemic stroke due to LVO in the anterior circulation treated with MT after IVT To evaluate treatment outcomes and some predictive factors in patients with acute ischemic stroke due to LVO in the anterior circulation treated with MT after IVT NEW POINTS OF THE THESIS The research supplied information on some clinical and subclinical characteristics in patients with acute ischemic stroke due to LVO in the anterior circulation treated with bridging therapy Bridging therapy showed high rates of successful recanalization and favorable outcomes and low rates of severe complications, in which recovery outcomes did not differ between tPA doses Still, mortality after three months was higher in the standard-dose group In addition, it revealed factors affecting treatment outcomes, of which 24-hour NIHSS is an independent prognostic factor for recovery after three months and futile revascularization outcomes THE STRUCTURE OF THE THESIS The thesis consists of 123 pages and includes Introduction (2 pages), Overview (34 pages), Subjects and Methods (20 pages), Results (24 pages), Discussions (40 pages), Conclusions (2 pages), and Recommendations (1 page); with four chapters, 32 tables, 14 charts, 23 figures, two diagrams, and 177 references ABBREVIATIONS ASPECTS: Alberta stroke program early computed tomography scale, CI: confidence interval, CT: computed tomography, CTA: computed tomography angiography, GCS: Glasgow coma scale, ICH: intracranial hemorrhage, IVT: intravenous thrombolysis, LVO: large vessel occlusion, MRI: magnetic resonance imaging, mRS: modified Rankin scale, MT: mechanical thrombectomy, NIHSS: National Institutes of Health stroke scale, tPA: tissue plasminogen activator CHAPTER – OVERVIEW 1.1 Anatomy of cerebral arteries The brain receives blood from the anterior and posterior circulations, which the Circle of Willis mainly connects Cerebral perfusion can be supported by collateral circulation in three different ways, and these anastomoses maintain the blood flow after the partial blockage of primary vascular pathways 1.2 Ischemic stroke due to LVO Ischemic stroke due to LVO can occur through four different mechanisms The lower the cerebral blood flow thresholds, the more severe the disorders and consequences Besides the irreversible infarct core, the penumbra can be recovered with timely reperfusion Clinical symptoms of ischemic stroke due to LVO usually follow cerebral vascular territories The location and number of occlusive vessels in acute ischemic stroke affect stroke severity and clinical outcomes The risk factors of LVO are like those of ischemic stroke in general, with comparable rates, except atrial fibrillation, with significantly higher rates Neuroimaging helps to diagnose, differentiate, and evaluate cerebral vessels, estimate infarct core and penumbra, and provide evidence for reperfusion therapy Those rely on CT and MRI, and digital subtraction angiography mainly applies for recanalization Other subclinical examinations aid in detecting the underlying causes of stroke and associated conditions 1.3 Reperfusion therapy for acute ischemic stroke IVT is used to treat acute ischemic stroke within 4.5 hours and can be applied in a 4.5-9-hour window when there is evidence of CT or MRI core/perfusion mismatch and MT is either not indicated or not planned The standard dose of tPA is 0.9 mg/kg, besides 0.6 mg/kg and other low doses (between 0.6-0.9 mg/kg) Complications: ICH, systemic hemorrhage, and oral and tongue angioedema MT is to approach endovascularly to occluded sites to revascularize There are clinical and subclinical criteria for MT in the 0-6-hour window The 6-24-hour window requires perfusion imaging, but MT can be considered if there is a clinical/ASPECTS mismatch The most widely used two main categories of MT devices are stentrievers (e.g., Solitaire) and aspiration catheters Complications include infarcts in new territory, ICH or death, and procedure complications Combining IVT and MT is also known as bridging therapy For ischemic stroke within 4.5 hours and eligible for both IVT and MT, IVT should be started as soon as possible before MT 1.4 Relevant studies on the thesis A series of international trials in 2015 proved the efficacy of MT on ischemic stroke due to LVO of anterior circulation Studies comparing bridging and MT alone have not demonstrated the superiority of MT alone Some studies comparing tPA doses during bridging therapy found no difference However, they have a low evidence level, and the number of studies still needs to be more significant Domestic studies have mainly been on MT in general; few studies solely focus on bridging therapy; not all doses of IVT have been evaluated; and little attention has been paid to prognostic factors for treatment outcomes 1.5 Existing issues to be solved in the thesis Clinical and subclinical features in acute ischemic stroke patients are treated with different doses of tPA when IVT precedes MT What the outcomes are, and what factors affect outcomes in acute ischemic stroke patients treated with bridging therapy CHAPTER – SUBJECTS AND METHODS 2.1 Subjects Seventy-nine patients with acute ischemic stroke due to anterior circulation LVO were treated with bridging therapy at 115 People's Hospital and Nghe An Friendship General Hospital from June 2016 to November 2019 2.1.1 Criteria of patient selection Age ≥ 18, clinically consistent with acute stroke, IVT ≤ 270 with standard dose or low dose of tPA and MT with Solitaire (onset to puncture ≤ 360 minutes), NIHSS ≥ and < 30, occlusion of the internal carotid artery, middle cerebral artery – M1, M2 segments, ASPECTS ≥ 2.1.2 Exclusion criteria Absolute contraindications for IVT and MT, failure to approach occlusion site, failure to assess/no contact after 90 days 2.2 Materials and methods 2.2.1 Study design: a prospective descriptive study with follow-up 2.2.2 Sample size 𝑍1−𝛼/2 +𝑍1−𝛽 Sample size formula: 𝑁 = × ( 𝛿0 ) × 𝑝 × (1 − 𝑝) 𝑁-sample size of the study; 𝛼-error type I, 𝛼 = 0.05, corresponding reliability is 𝑍1−𝛼/2 =1.96; 𝛽-error type II, 𝛽 =0.8 with 𝑍1−𝛽 =0.842; 𝑝-the ratio of mRS 0-2 after 90 days of the EXTEND-IA trial was 0.71; 𝛿0 -margin of error, 𝛿0 =0.25 The minimum number of patients is 𝑁 = 52 (convenience sampling) 2.2.3 Research variables and evaluation criteria Demographic characteristics: age, gender Risk factors for stroke and related history Clinical variables include symptoms at onset and admission, vital signs, and NIHSS Subclinical variables: blood test results, ASPECTS, vascular lesions, and other imaging features, cardiac and carotid ultrasound Time variables: onset, admission, and others Variables on IVT and MT, evaluation of treatment efficacy and complications; mRS, death, futile recanalization after three months 2.2.4 Techniques and data collection tools Examination, obtaining medical history; observation, evaluation, and use of the information on subclinical tests and imaging; interview with patients and family members during follow-up 2.2.5 Steps to conduct research 2.2.5.1 Within the first 24 hours Acute stroke patients (0-4.5 hours) were obtained a medical and related history and examined clinically and subclinically with head CT/MRI scans and other tests IVT was given first (standard or low dose) before MT Monitoring closely, receiving the best medical treatment, and performing head CT scan if ICH was suspected 2.2.5.2 After 24-48 hours Monitoring and evaluation, CT/MRI could be re-done to evaluate vessels, brain damage, and ICH Receiving the best medical treatment 2.2.5.3 The following days until discharge Clinical monitoring and evaluation, preventing and managing other complications and events during hospitalization 2.2.5.4 Three months after the stroke Evaluate the degree of disability/dependence (mRS), including death 2.2.6 Statistical analysis Data entry, processing, and analysis using SPSS 25.0: Descriptive statistics, scale comparisons, mean/median comparisons (including paired-samples t-test), univariate and multivariate binary logistic analysis; A p-value < 0.05 is statistically significant CHAPTER – RESULTS 3.1 Some clinical and subclinical features 3.1.1 Age and gender characteristics The median age was 57.9 ± 13.3 years, with the most common age being 40-59 (46.8%) Males 57% (the male-female ratio is 1.3:1) 3.1.2 Risk factors and history characteristics Dyslipidemia, hypertension, and atrial fibrillation were most common (79.7%, 63.3,% and 43%) 16.5% of patients took antiplatelet agents or anticoagulants before stroke (69.2% took vitamin K antagonists) 3.1.3 Symptoms at onset and at admission The most common symptom was hemiplegia (96.2% at onset, 100% on admission) Symptoms were more adequate at admission than at onset 3.1.4 Vital signs upon admission Mean GCS was 13.8; most vital signs were in the physiological or stable range and did not require emergency management 3.1.5 Admission NIHSS and time characteristics Mean/median of admission NIHSS were 13/13.5 Rate of NIHSS 9-15 was 41.8% The mean/median of onset-to-needle time was 160/165 minutes, the median of tPA bolus-groin puncture was 85 minutes 92.3% 87.2% 78.9% 100% 50% 50% 7.7% 12.8% 21.1% 2016 2017 2018 < 60 ≥ 60 0% 2019 Figure 3.7 Classification of tPA bolus-groin puncture time by year 17.7% of patients started MT within < 60 minutes of the start of IVT, and the rate increased year-on-year, which was statistically significant when analyzing univariate logistic regression 3.1.6 Blood test characteristics Most blood test results are within physiological thresholds, with only a handful of abnormalities, such as severe anemia or a peak INR of 1.37, that did not violate the absolute contraindications of IVT Taking vitamin K antagonists increases the rate of INR > 1.1 3.1.7 Imaging characteristics ASPECTS on admission were mainly high, as shown by the median and mean of and 8.75, respectively, and nearly 2/3 of patients had ASPECTS of 9-10 6.3% 2.5% ICA ICA & MCA (tandem lesion) 17.7% ICA & MCA (not tandem lesion) M1 MCA 63.3% M2 MCA Figure 3.8 Locations of the occlusion 10.1% ICA: internal carotid artery, MCA: middle cerebral artery The majority of occlusions were at M1 segments Most patients had right-sided occlusion (62%), and only 21.5% had intracranial artery stenosis on the same side of the occlusion Table 3.8 Collateral circulation and classification Collateral circulation Value Percentage Classification Score 0 6.1 Poor 71.4 16 32.7 16 32.7 10 20.4 Good 28.6 8.2 Sum 49 100 28.6% were rated as having good collateral circulation ASPECTS 910 rate was higher in patients with good collateral circulation 11 After three months, 77.2% had good recovery results (mRS 0-2), and eight patients (10.1%) died The futile recanalization rate was 19.7% 3.2.5 Factors affecting mRS results after three months The 0-2 mRS group was compared with the mRS 3-6 group: the 0-2 mRS group had higher mean/median of GCS (14.2/15 versus 12.5/12), lower means/medians of admission NIHSS (12.3/12 versus 17.4/17), 24-hour NIHSS (4.7/4 versus 16.9 /16.5), lower rates of deviation of eyes and head (26.2% versus 61.1%); higher rates of TICI 2b-3 (100% versus 83.3%) and TICI (62.3% versus 33.3%), lower rates of general ICH (26.2% versus 61.1%), symptomatic ICH (0% versus 27.8%) and other complications (14.8% versus 38.9%) Table 3.19 Association between influencing factors and mRS outcomes after three months Logistic regression Univariate Independent variable OR 95% CI p* Admission GCS** Admission NIHSS** 24-hour NIHSS** Deviation of eyes and head TICI ICH Other complications during hospitalization 0.498 1.236 1.532 4.420 0.303 4.420 0.337-0.738 1.090-1.400 1.246-1.883 1.462-13.359 0.100-0.917 1.462-13.359 0.001 0.001 < 0.001 0.008 0.035 0.008 3.677 1.127-11.998 0.031 Admission GCS** 0.365 0.067-1.997 Admission NIHSS** 0.599 0.297-1.209 24-hour NIHSS** 2.400 1.178-4.891 Deviation of eyes and head 31.321 0.706-1389.8 Multivariate TICI 0.130 0.004-3.920 Yes ICH 470.5 0.47-470634 Other complications 0.383 0.004-39.131 during hospitalization *Binary Logistic Regression, **every 01 point increases 0.245 0.152 0.016 0.075 0.240 0.081 0.684 12 All the above factors had statistically significant effects in the univariate logistic regression analysis Only 24-hour NIHSS has independent prognostic value in the multivariate analysis 3.2.6 Factors affecting survival-death outcomes after three months Survival group versus death group: higher mean GCS (14 versus 12), lower rate of atrial fibrillation (38% versus 87.5%), lower means/medians of both admission NIHSS (12.9/13 versus 18.7/17) and 24-hour NIHSS (6/4 versus 20.3/22); lower rates of INR > 1.1 (25.4% versus 62.5%), standard-dose IVT (45.1% versus 87.5%), symptomatic ICH (1.4% versus 50%), and other complications during hospitalization (12.7% versus 87.5%) Table 3.23 Association between predisposing factors and survivaldeath outcomes after three months Logistic regression Independent variable OR 95% CI p* Admission GCS** 0.520 0.335-0.808 0.004 Admission NIHSS** 1.248 1.058-1.472 0.009 24-hour NIHSS** 1.311 1.140-1.508 < 0.001 Atrial fibrillation 11.407 1.330-97.87 0.026 Univariate INR > 1.1 4.907 1.065-22.617 0.041 Standard-dose IVT 8.531 0.997-73.0 0.05 Symptomatic ICH 70.0 6.275-780.8 0.001 Other complications 48.222 5.296-439.1 0.001 during hospitalization Multivariate Admission GCS** Admission NIHSS** 24-hour NIHSS** Atrial fibrillation INR > 1.1 Symptomatic ICH Other complications during hospitalization 0.662 0.189-2.321 0.519 0.774 0.338-1.775 0.546 1.445 0.836-2.496 0.187 18.253 0.286-1164.6 0.171 14.301 0.131-1563.9 0.267 0.447 0.000-14274 0.879 32.094 0.706-1459.7 0.075 *Binary Logistic Regression, **every 01 point increases The univariate analysis showed that admission GCS, admission NIHSS, 24-hour NIHSS, atrial fibrillation, INR > 1.1, and symptomatic ICH 13 affected survival-dead outcomes significantly, were analyzed in the multivariate analysis None of them had independent prognostic value The standard-dose rate for IVT was statistically higher in the INR > 1.1 group than in the INR ≤ 1.1 group The percentage of symptomatic ICH was higher in the INR > 1.1 group than in the INR ≤ 1.1 group but was not statistically significant Rate of symptomatic ICH in the standarddose IVT group was statistically significantly higher than the low-dose IVT group’s one (12.8% versus 0%) 3.2.7 Factors affecting futile recanalization Table 3.25 Association between influencing factors and futile recanalization Logistic regression Independent variable Admission GCS** Admission NIHSS** 24-hour NIHSS** Univariate Atrial fibrillation ICH Other complications during hospitalization Multivariate Admission GCS** Admission NIHSS** 24-hour NIHSS ** Atrial fibrillation ICH Other complications during hospitalization OR 0.496 1.216 1.509 3.304 5.625 95% CI p* 0.330-0.745 0.001 1.070-1.382 0.003 1.224-1.859 1.1, standarddose IVT, symptomatic ICH and other complications during hospitalization in general None of these factors have independent prognostic value + Effects on futile revascularization: GCS, admission NIHSS, 24-hour NIHSS, atrial fibrillation, ICH, and other complications during hospitalization in general The 24-hour NIHSS has an independent prognostic value (OR = 2.102) 24 RECOMMENDATIONS Consider a low dose of tPA in bridging therapy for patients with acute ischemic stroke due to LVO because there was no difference in recovery outcomes but higher 3-month mortality with the standard dose Rescue angioplasty by balloon can be suggested in patients with MT failure in cases of intracranial artery stenosis when indicated to increase the rate of reasonable revascularization LIST OF PUBLISHED ARTICLES RELATING TO THE THESIS Nguyen Thanh Long, Duong Dinh Chinh, Ngo Tien Tuan (2018), Results of bridging therapy with intravenous thrombolysis and mechanical thrombectomy in patients with acute anterior circulation ischemic stroke, Journal of 108 – Clinical Medicine and Pharmacy, (13), pp 10-15 Nguyen Thanh Long, Duong Dinh Chinh, Ngo Tien Tuan (2020), Results of bridging therapy with standard-dose versus nonstandard-dose intravenous thrombolysis and mechanical thrombectomy in acute ischemic stroke patients, Vietnam Medical Journal, (497), pp 218-224 Nguyen Thanh Long, Duong Dinh Chinh, Ngo Tien Tuan (2020), Predictive factors of outcomes in acute ischemic stroke patients treated by bridging therapy with standard-dose versus nonstandard-dose intravenous thrombolysis plus mechanical thrombectomy, Vietnam Medical Journal, 2020, (497), pp 198204