Thrombolysis improves reperfusion and the clinical outcome in tandem occlusion stroke related to cervical dissection: TITAN and ETIS pooled analysis

BACKGROUND AND PURPOSE: Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT. METHODS: We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0-1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80). CONCLUSIONS: Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome

Increased blood pressure variability and the risk of probable dementia or mild cognitive impairment: A post hoc analysis of the SPRINT MIND trial

Background Increased systolic blood pressure variability (BPV) is associated with stroke, cardiovascular disease, and dementia and mild cognitive impairment. However, prior studies assessing the relationship between BPV and dementia or mild cognitive impairment had infrequent measurement of blood pressure or suboptimal blood pressure control. Methods and Results We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) MIND (Memory and Cognition in Decreased Hypertension) trial. The primary outcome was probable dementia during follow-up. We defined our exposure period, during which blood pressures were collected, as the first 600 days of the trial, and outcomes were ascertained during the subsequent follow-up. BPV was measured as tertiles of systolic blood pressure standard deviation. We fit Cox proportional hazards models to our outcome. We included 8379 patients. The mean follow-up was 3.2±1.4 years, during which 316 (3.8%) patients developed dementia. The mean number of blood pressure measurements was 7.8, and in the tertiles of BPV, the SD was 6.3±1.6, 10.3±1.1, and 16.3±3.6 mm Hg, respectively. The rate of dementia was 2.4%, 3.6%, and 5.4% by ascending tertile, respectively

Characteristics and outcomes among US patients hospitalized for ischemic stroke before vs during the COVID-19 pandemic

Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19. Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if they were admitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 discharged between January and March 2020 were excluded from the analysis because they had unreliable data on COVID-19 status, leaving 282 847 patients for the study. Exposure: Ischemic stroke and laboratory-confirmed COVID-19. Main Outcomes and Measures: Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were discharged in 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non-COVID-19 groups, respectively) who were discharged between April and December 2020. Results: Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non-COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13 846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10 846 patients in April 2020 before returning to a prepandemic level of 13 639 patients by July 2020. A mean (SD) of 13 492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non-COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05). Conclusions and Relevance: In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbidity was high

Impact of Emergent Cervical Carotid Stenting in Tandem Occlusion Strokes Treated by Thrombectomy: A Review of the TITAN Collaboration

Introduction: Endovascular therapy has been shown to be an effective and safe treatment for tandem occlusion. The endovascular therapeutic strategies for tandem occlusions strokes have not been adequately evaluated and the best approach is still controversial. The TITAN (Thrombectomy in TANdem occlusions) registry was a result of a collaborative effort to identify the best therapeutic approach for acute ischemic stroke due to tandem lesion. In this review, we aim to summarize the main findings of the TITAN study and discuss the challenges of treatment for tandem occlusion in the era of endovascular thrombectomy.Methods: A review of the data from the multicenter international observational and non-randomized TITAN registry was performed. The TITAN registry included acute ischemic stroke patients with tandem lesions (proximal intracranial occlusion and cervical carotid artery occlusion or stenosis>90%) who were treated with thrombectomy with or without carotid artery stenting.Results: Prior intravenous thrombolysis and emergent cervical carotid stenting were associated with higher reperfusion (mTICI 2b-3 and mTICI 3) rates at the end of the intervention. Poor outcome did not occur more frequently after stenting than after conservative treatment of the cervical carotid lesion. Emergent carotid stenting with antithrombotic agents and intracranial thrombectomy yielded higher reperfusion rate and good outcome (90 day mRS 0–2) compared to other strategies (carotid artery stenting and thrombectomy without antithrombotic, angioplasty and thrombectomy, or thrombectomy alone). Pretreatment intravenous thrombolysis was not associated with increased risk of hemorrhagic complications. Likewise, periprocedural unfractionated heparin did not modify the efficacy and safety results. Etiology of carotid artery lesion (atherosclerosis vs. dissection) did not emerge as predictor of outcome or recanalization.Conclusion: Emergent stenting of the cervical carotid lesion with antithrombotic agents in conjunction to thrombectomy appears to be the best treatment strategy for acute ischemic strokes with tandem lesions. These findings will be further investigated in the ongoing randomized controlled TITAN trial

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy : a systematic review and meta-analysis of observational data

Background Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin ScalePeer reviewe

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry

Introduction Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. Methods A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (>= 90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. Results A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259 +/- 120 min vs 305 +/- 202 min;p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%;p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. Conclusion Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty

Conscious Sedation versus Local Anesthesia During Thrombectomy for Acute Ischemic Stroke, Do We Have a Winner?

International audienc

Impact of mean blood pressure and blood pressure variability after diagnosis of mild cognitive impairment and risk of dementia

Abstract Hypertension and increased blood pressure variability (BPV) are associated with the development of dementia. However, previous studies did not focus on the risk of dementia among participants with mild cognitive impairment (MCI) and controlled blood pressure level. To address this limitation, the authors performed a post‐hoc analysis of SPRINT MIND participants diagnosed with MCI (mean Montreal Cognitive Assessment score at diagnosis 16.1±3.1). The primary outcome was subsequent diagnosis of probable dementia. The exposure was mean blood pressure and BPV following MCI diagnosis until the end of follow‐up or a dementia event (mean follow‐up 2.6±1.2 years). The primary outcome occurred in 76/516 (14.7%) patients. The mean blood pressure was not significantly higher in participants who developed dementia. In the lowest quartile of BPV (systolic standard deviation), the rate of dementia was 8.5% (11/129), while in the highest quartile it was 21.7% (28/129). The highest quartile of systolic BPV had an adjusted hazard ratio for dementia of 2.73 (95% CI, 1.31–5.69) and for diastolic BPV it was 2.62 (95% CI, 1.26–5.47). In SPRINT MIND participants, the authors found that increased BPV after MCI diagnosis was associated with incident probable dementia during subsequent follow‐up