3-month Favorable Functional Outcome Research Articles

IV Thrombolysis in Basilar Artery Occlusion: Outcomes and Comparison With Endovascular Thrombectomy.

Recanalization is considered a prerequisite for favorable outcome in basilar artery occlusion (BAO). Intravenous thrombolysis (IVT) has been successfully used for eligible patients with BAO well beyond the 4.5-hour time window but has been largely underrepresented in the best medical management arms in recent randomized controlled trials of recanalization therapy in BAO. We aimed to analyze the outcomes of patients with BAO treated with IVT only and to compare IVT with endovascular thrombectomy (EVT). This observational single-center, retrospective cohort study included consecutive patients with BAO treated with IVT and/or EVT up to 48 hours of symptom onset during 1995-2022. The primary outcome was favorable functional outcome (modified Rankin Scale 0-3) at 3 months collected by a stroke physician by phone. In the first part, we described the outcomes and factors associated with functional outcome in the IVT-only cohort during 1995-2022. In the second part, we used doubly robust inverse probability-weighted regression adjustment models to compare functional outcome of patients treated with IVT vs EVT+/-IVT during 2010-2022. In the whole cohort of 376 patients with acute BAO treated with recanalization therapy, 245 (65.2%) received only IVT. In the IVT-only cohort, most patients had moderate-to-severe clinical presentation (median NIH Stroke Scale 18) but no extensive early ischemic changes in the posterior circulation on admission. Half of them had onset-to-treatment time over 6 hours. 46.5% of the IVT-treated patients achieved 3-month favorable functional outcome, whereas mortality was 35.9%. sICH occurred in 11.1%. In a multivariable analysis, younger age, milder symptom severity, and less baseline ischemic changes predicted favorable functional outcome. In the 2010-2022 cohort, when compared with patients treated with EVT+/-IVT (n = 121), the IVT-only cohort (n = 122) had higher odds for favorable functional outcome (IVT 58.2% vs EVT 43.0% (aOR 2.82 [95% CI 1.31-6.05]). IVT alone produced outcomes comparable with those in recent trials of endovascular BAO recanalization. Furthermore, in head-to-head comparison in our cohort, the IVT-only approach was more often associated with favorable outcome than EVT+/-IVT. Thus, it should not be overlooked as the first-line recanalization therapy in acute BAO, even in longer time windows. This study provides Class IV evidence that tPA is as effective as thrombectomy for basilar artery thrombosis.

Advanced Neuroimaging Preceding Intravenous Thrombolysis in Acute Ischemic Stroke Patients Is Safe and Effective.

Advanced neuroimaging is one of the most important means that we have in the attempt to overcome time constraints and expand the use of intravenous thrombolysis (IVT). We assessed whether, and how, the prior use of advanced neuroimaging (AN), and more specifically CT/MR perfusion post-processed with RAPID software, regardless of time from symptoms onset, affected the outcomes of acute ischemic stroke (AIS) patients who received IVT. Methods. We retrospectively evaluated consecutive AIS patients who received intravenous thrombolysis monotherapy (without endovascular reperfusion) during a six-year period. The study population was divided into two groups according to the neuroimaging protocol used prior to IVT administration in AIS patients (AN+ vs. AN−). Safety outcomes included any intracranial hemorrhage (ICH) and 3-month mortality. Effectiveness outcomes included door-to-needle time, neurological status (NIHSS-score) on discharge, and functional status at three months assessed by the modified Rankin Scale (mRS). Results. The rate of IVT monotherapy increased from ten patients per year (n = 29) in the AN− to fifteen patients per year (n = 47) in the AN+ group. Although the onset-to-treatment time was longer in the AN+ cohort, the two groups did not differ in door-to-needle time, discharge NIHSS-score, symptomatic ICH, any ICH, 3-month favorable functional outcome (mRS-scores of 0–1), 3-month functional independence (mRS-scores of 0–2), distribution of 3-month mRS-scores, or 3-month mortality. Conclusion. Our pilot observational study showed that the incorporation of advanced neuroimaging in the acute stroke chain pathway in AIS patients increases the yield of IVT administration without affecting the effectiveness and safety of the treatment.

Intravenous thrombolysis in patients with chronic kidney disease: A systematic review and meta-analysis.

To determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS). A systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0-1), and 3-month functional independence (FI, mRS score 0-2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60-89 mL/min) to moderate (eGFR 30-59 mL/min) to severe (eGFR 15-29 mL/min). We identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01-1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18-1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72-2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47-0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46-0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01-1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27-3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01-1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09-1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70-0.92). After adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity

We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores<6 points. The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63±15years, 45% women). Patients treated with IVT (n=162) had higher FI (85.6% vs. 74.8%, P=0.027) with lower mRS scores at hospital discharge (P=0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Abstract WP112: Thrombolysis for AIS in the Unwitnessed or Extended Therapeutic Time Window: A Systematic Review and Meta-Analysis

Introduction: We sought to assess the utility of intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients with unclear symptom onset time or outside the 4.5 hour time window, selected by advanced neuroimaging. Methods: We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome [FFO, modified Rankin Scale (mRS) scores: 0-1], 3-month functional independence (FI, mRS-scores: 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS-scores), symptomatic intracranial hemorrhage (sICH) and complete recanalization (CR). Results: We identified 4 eligible RCTs (859 total patients). In unadjusted analyses IVT was associated with higher likelihood of 3-month FFO (OR=1.48, 95%CI:1.12-1.96), FI (OR=1.42, 95%CI:1.07-1.90), sICH (OR=5.28, 95%CI:1.35-20.68) and CR (OR=3.29, 95%CI:1.90-5.69), with no significant difference in the odds of all-cause mortality risk at three months (OR=1.75, 95%CI: 0.93-3.29). In the adjusted analyses IVT was also associated with higher odds of 3-month FFO (OR adj =1.62, 95%CI:1.20-2.20), functional improvement (OR adj =1.42, 95%CI: 1.11-1.81) and sICH (OR adj =6.22, 95%CI: 1.37-28.26). There was no association between IVT and FI (OR adj =1.61, 95%CI: 0.94-2.75) or all-cause mortality at three months (OR adj =1.75, 95%CI: 0.93-3.29). No evidence of heterogeneity was evident in any of the analyses (I 2 =0). Conclusion: IVT in AIS patients with unknown symptom onset time or elapsed time from symptom onset more than 4.5 hours, selected with advanced neuroimaging, results in a higher likelihood of complete recanalization and functional improvement at three months despite the increased risk of sICH.

Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke

Background and PurposeAlthough onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. MethodsWe conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0–1 and 0–2 respectively. ResultsWe enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (jos-2019-01648P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). ConclusionsEarlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time results in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Safety and efficacy of dual antiplatelet pretreatment in patients with ischemic stroke treated with IV thrombolysis: A systematic review and meta-analysis.

Conflicting data exist on the safety and efficacy of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) receiving dual antiplatelet pretreatment (DAPP). The aim of the present systematic review and meta-analysis is to assess the safety and outcome of DAPP history among patients with AIS treated with IVT. We performed a comprehensive literature review to identify studies that investigated the safety and efficacy of DAPP among patients with AIS treated with IVT. We identified 9 studies comprising 66,675 patients. In unadjusted analyses, DAPP was associated with a higher likelihood of pooled symptomatic intracranial hemorrhage (sICH; odds ratio [OR] 2.26; 95% confidence interval [CI] 1.39-3.67) and 3-month mortality (OR 1.47; 95% CI 1.25-1.73). DAPP was also related to higher odds of sICH according to Safe Implementation of Treatments in Stroke Monitoring Study (OR 2.71; 95% CI 2.05-3.59), European Cooperative Acute Stroke Study II (OR 2.23; 95% CI 1.46-3.40), and National Institute of Neurological Disorders and Stroke (OR 1.59, 95% CI 1.38-1.83) definitions. There was no association between DAPP and 3-month favorable functional outcome (FFO, modified Rankin Scale [mRS] score 0-1) and 3-month functional independence (FI; mRS score 0-2). In adjusted analyses, history of DAPP was not associated with pooled sICH (OR 2.03; 95% CI 0.75-5.52), 3-month mortality (OR 1.11; 95% CI 0.87-1.40), 3-month FFO (OR 0.92; 95% CI 0.77-1.09), and 3-month FI (OR 1.01; 95% CI 0.89-1.15). After adjustment for potential confounders, DAPP appears not to be associated with higher risk of adverse outcomes in patients with AIS treated with IVT.

Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window.

To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging. We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR). We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [ORadj] 1.62, 95% CI 1.20-2.20), functional improvement (ORadj 1.42, 95% CI 1.11-1.81), and sICH (ORadj 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94-2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I 2 = 0). IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.

Medical Management vs Mechanical Thrombectomy for Mild Strokes

The benefit of mechanical thrombectomy (MT) in patients with stroke presenting with mild deficits (National Institutes of Health Stroke Scale [NIHSS] score <6) owing to emergency large-vessel occlusion (ELVO) remains uncertain. To assess the outcomes of patients with mild-deficits ELVO (mELVO) treated with MT vs best medical management (bMM). We retrospectively pooled patients with mELVO during a 5-year period from 16 centers. A meta-analysis of studies reporting efficacy and safety outcomes with MT or bMM among patients with mELVO was also conducted. Data were analyzed between 2013 and 2017. We identified studies that enrolled patients with stroke (within 24 hours of symptom onset) with mELVO treated with MT or bMM. Efficacy outcomes included 3-month favorable functional outcome and 3-month functional independence that were defined as modified Rankin Scale scores of 0 to 1 and 0 to 2, respectively. Safety outcomes included 3-month mortality and symptomatic and asymptomatic intracranial hemorrhage (ICH). We evaluated a total of 251 patients with mELVO who were treated with MT (n = 138; 65 women; mean age, 65.2 years; median NIHSS score, 4; interquartile range [IQR], 3-5) or bMM (n = 113; 51 women; mean age, 64.8; median NIHSS score, 3; interquartile range [IQR], 2-4). The rate of asymptomatic ICH was lower in bMM (4.6% vs 17.5%; P = .002), while the rate of 3-month FI (after imputation of missing follow-up evaluations) was lower in MT (77.4% vs 88.5%; P = .02). The 2 groups did not differ in any other efficacy or safety outcomes. In multivariable analyses, MT was associated with higher odds of asymptomatic ICH (odds ratio [OR], 11.07; 95% CI, 1.31-93.53; P = .03). In the meta-analysis of 4 studies (843 patients), MT was associated with higher odds of symptomatic ICH in unadjusted analyses (OR, 5.52; 95% CI, 1.91-15.49; P = .002; I2 = 0%). This association did not retain its significance in adjusted analyses including 2 studies (OR, 2.06; 95% CI, 0.49-8.63; P = .32; I2 = 0%). The meta-analysis did not document any other independent associations between treatment groups and safety or efficacy outcomes. Our multicenter study coupled with the meta-analysis suggests similar outcomes of MT and bMM in patients with stroke with mELVO, but no conclusions about treatment effect can be made. The clinical equipoise can further be resolved by a randomized clinical trial.

Association of Baseline Hyperglycemia With Outcomes of Patients With and Without Diabetes With Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Propensity Score-Matched Analysis From the SITS-ISTR Registry.

Available data from observational studies on the association of admission hyperglycemia (aHG) with outcomes of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are contradictory, especially when stratified by diabetes mellitus (DM) history. We assessed the association of aHG (≥144 mg/dL) with outcomes stratified by DM history using propensity score-matched (PSM) data from the SITS-ISTR. The primary safety outcome was symptomatic intracranial hemorrhage (SICH); 3-month functional independence (FI) (modified Rankin Scale [mRS] scores 0-2) represented the primary efficacy outcome. Patients with and without aHG did not differ in baseline characteristics both in the non-DM (n = 12,318) and DM (n = 6,572) PSM subgroups. In the non-DM group, patients with aHG had lower 3-month FI rates (53.3% vs. 57.9%, P < 0.001), higher 3-month mortality rates (19.2% vs. 16.0%, P < 0.001), and similar symptomatic intracerebral hemorrhage (SICH) rates (1.7% vs. 1.8%, P = 0.563) compared with patients without aHG. Similarly, in the DM group, patients with aHG had lower rates of 3-month favorable functional outcome (mRS scores 0-1, 34.1% vs. 39.3%, P < 0.001) and FI (48.2% vs. 52.5%, P < 0.001), higher 3-month mortality rates (23.7% vs. 19.9%, P < 0.001), and similar SICH rates (2.2% vs. 2.7%, P = 0.224) compared with patients without aHG. In conclusion, aHG was associated with unfavorable 3-month clinical outcomes in patients with and without DM and AIS treated with IVT.

Intra-Arterial Thrombolysis Improves the Prognosis of Acute Ischemic Stroke Patients without Large Vessel Occlusion

Background and Purpose: Intravenous thrombolysis is known as the only effective reperfusion therapy for acute ischemic stroke (AIS) caused by small branches occlusion. However, it is still unclear whether intra-arterial thrombolysis (IAT) is safe and effective for patients without detectable arterial occlusion. This study evaluated the safety and efficacy of IAT in these patients. Methods: Data were collected on consecutive patients from December 2012 to February 2017 at the Xuanwu Hospital, Capital Medical University. AIS patients without large artery occlusion during digital subtraction angiography (DSA) were divided into 2 groups: (1) Intra-arterial urokinase thrombolysis group (UK group): received intra-arterial urokinase thrombolysis treatment; (2) Control group: cerebral angiography examination only. The primary outcome was 3-month favorable functional outcome (modified Rankin Scale 0–2). Results: A total of 48 patients received urokinase thrombolysis, and 34 patients underwent DSA examination only. The UK group had more frequent favorable functional outcomes (70.8 vs. 50%, p = 0.032) at 3-month follow-up and higher score of National Institutes of Health Stroke Scale improvement on the second day (p = 0.007). One patient (2%) had symptomatic intracerebral hemorrhage and 3 patients (6.3%) had asymptomatic intracerebral hemorrhage (asICH) in the UK group. One patient (3.3%) had asICH in the control group. There were no significant differences about ICH. Conclusions: AIS caused by small branches occlusion could benefit from intra-arterial urokinase thrombolysis, and the risk of intracerebral hemorrhage was not significantly higher.

Abstract WP106: Timing of Tissue-plasminogen-activator Induced Recanalization and Functional Recovery in Acute Ischemic Stroke

Introduction: Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes in AIS remains debatable. Methods: We sought to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler (TCD) monitoring is independently associated with improved 3-month outcomes in tPA-eligible patients with proximal intracranial arterial occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale scores of 0-1 and 0-2 respectively. Results: We prospectively enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline NIHSS score 15) during a 7-year period from 12 participating centers. Complete or partial early recanalization was detected in 53% of patients. Patients with early recanalization had (p&lt;0.001) higher rates of 2-hour DCR (54% vs. 10%), 3-month FFO (67% vs. 28%), FI (81% vs. 39%) and lower mortality rates (6% vs. 17%) compared to patients with persisting occlusions. In multivariable analyses, recanalization during tPA infusion was independently (p&lt;0.05) associated with higher probability of three-month FFO and lower likelihood of three-month mortality. Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (Spearman’s rho= +0.151, p=0.009). Conclusions: Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time results in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Association of Elevated Blood Pressure Levels with Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

Background and PurposeAlthough arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes. MethodsEligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0–1) and 3-month functional independence (mRS scores of 0–2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed using random-effects models. ResultsWe identified 26 studies comprising 56,513 patients. Higher pre- (P=0.02) and posttreatment (P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment (P<0.001) SBP whereas trended towards lower pre-treatment (P=0.06) SBP. In adjusted analyses, elevated pre- (ORadj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (ORadj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (ORadj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (ORadj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence. ConclusionsWe found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association.

Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis

To determine the association of differential leukocyte counts on admission with efficacy and safety outcomes in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). Consecutive patients with AIS receiving IVT were evaluated at two stroke centers. Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were determined during the initial 12 h of admission. Efficacy outcomes were favorable functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality. Among 657 IVT-treated patients with AIS, the mean age was 64 ± 14 years, 50% were female and median National Institutes of Health Stroke Scale score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte counts and NLR counts were observed in patients with 3-month FFO and FI, whereas higher counts were observed in patients who died at 3 months. The best discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%, specificity 63.1%) and leukocyte count <8100/μL (sensitivity 57.5%, specificity 55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/μL demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014) and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001). Combined neutrophil (<6800/μL) and leukocyte (<8100/μL) counts demonstrated a strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction = 0.012). Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets.

We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010-2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0-1); (4) 3-month functional independence (FI; mRS scores = 0-2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = -0.03 to -0.01), ECASS II (5.2% vs 4.4%, 95% CI = -0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = -0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = -0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = -0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = -0.03 to 0.06), or distribution in 3-month mRS scores (2 [1-4] vs 2 [0-4], 95% CI = -0.29 to 0.09) were documented between the 2 groups. Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89-97.

Intravenous thrombolysis for acute ischemic stroke in Greece: the Safe Implementation of Thrombolysis in Stroke registry 15-year experience.

Background:Intravenous thrombolysis (IVT) remains the only approved systemic reperfusion treatment for acute ischemic stroke (AIS), however there are scarce data regarding outcomes and complications of IVT in Greece. We evaluated safety and efficacy outcomes of IVT for AIS in Greece using the Safe Implementation of Thrombolysis in Stroke: International Stroke Thrombolysis Register (SITS-ISTR) dataset.Methods:All AIS patients treated with IVT in Greece between December 2002 and July 2017 and recorded in the SITS-ISTR were evaluated. Demographics, risk factors, baseline stroke severity [defined using National Institutes of Health Stroke Scale (NIHSS)], and onset-to-treatment time (OTT) were recorded. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality rates. The efficacy outcomes evaluated a reduction in baseline NIHSS score at 2 and 24 h following IVT onset, 3-month favorable functional outcome [FFO; modified Rankin scale (mRS) scores of 0–1] and 3-month functional independence (FI; mRS-scores of 0–2). The safety and efficacy outcomes were assessed comparatively with previously published data from SITS national and international registries.Results:A total of 523 AIS patients were treated with IVT in 12 Greek centers participating in the SITS-ISTR during the study period (mean age 62.4 ± 12.7; 34.6% women; median baseline NIHSS score: 11 points; median OTT: 150 min). The rates of sICH were 1.4%, 2.3%, and 3.8% according to the SIST-MOST, ECASS II, and NINDS criteria respectively. The median reduction in NIHSS score at 2 and 24 h was 3 [interquartile range (IQR): 1–5] and 5 (IQR: 2–8) points respectively. The 3-month FI, FFO and mortality were 66.5%, 55.6% and 7.9%. All safety and efficacy outcomes were comparable with available data from SITS-ISTR in other European countries.Conclusions:Our study underscores the safety and efficacy of IVT for AIS in Greece. Additional action is necessary in order to increase the availability of IVT in the Greek population and to include more centers in the SITS-ISTR.

Antiplatelet pretreatment and outcomes in intravenous thrombolysis for stroke: a systematic review and meta-analysis.

Since there are contradictory data regarding the association of antiplatelet pretreatment (AP) with safety and efficacy outcomes of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS), we conducted a systematic review and meta-analysis of available randomized-controlled clinical trials (RCTs) to investigate the association of AP with outcomes of AIS patients treated with intravenous alteplase. The outcome events of interest included symptomatic intracranial hemorrhage (sICH), fatal ICH, complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS score 0-1), 3-month functional independence (FI, mRS score 0-2), and mortality. The corresponding odds ratios (ORs) were calculated for all the outcome events using random-effects model. The adjusted age and admission NIHSS OR (ORadjusted) were also estimated for all available outcomes. We included 7 RCTs (4376 patients, 33.7% with AP). In unadjusted analyses, AP was associated with higher likelihood of sICH (OR=1.89, 95% CI 1.40-2.56), death (OR=1.59, 95% CI 1.24-2.03), and lower likelihood of 3-month FI (OR=0.69, 95% CI 0.56-0.85). No association was detected between AP and fatal ICH (OR=1.53, 95% CI 0.75-3.15), 3-month FFO (OR=0.79, 95% CI 0.58-1.07), and CR (OR=0.64, 95% CI 0.04-11.66). After adjustment for age and admission stroke severity, AP was not related to sICH (ORadjusted=1.67, 95% CI 0.75-3.72), 3-month FI (ORadjusted=0.88, 95% CI 0.54-1.42), or death (ORadjusted=1.01, 95% CI 0.55-1.86) in adjusted analyses. In conclusion, after adjusting for confounders, AP was not associated with a higher risk of sICH and worse 3-month functional outcome in AIS treated with intravenous alteplase. Antiplatelet intake prior to tPA-bolus should not be used as a reason to withhold or lower alteplase dose in AIS patients treated with IVT.

Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry.

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60min from symptom onset ("golden hour"), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(-)] the "golden hour" by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24h, respectively. A relative reduction in NIHSS-score of ≥40% at 2h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0-1 at 3months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(-) patients, with no differences in baseline characteristics (p>0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p<0.001) and 24h (41 vs. 27%; p=0.010), CREC at 2h (39 vs. 21%; p<0.001) and FFO (46.5 vs. 34.0%; p=0.028) at 3months. The rates of sICH and 3-month mortality did not differ (p>0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53-11.03) and CREC (OR: 2.38; 95% CI 1.38-4.09), 24-h CR (OR: 1.88; 95% CI 1.08-3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15-3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement.

Abstract 185: Association of Antiplatelet Pretreatment With Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Background &amp; Purpose: In a recent randomized controlled trial (RCT) of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) antiplatelet pre-treatment (APP) was associated with adverse outcomes. We conducted a systematic review and meta-analysis of available RCTs to investigate the association of APP with outcomes of AIS patients treated with IVT. Methods: The outcome events of interest included symptomatic intracranial hemorrhage (sICH), complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS-score: 0-1), functional independence (FI, mRS-score: 0-2), and mortality. Both unadjusted and adjusted (for baseline stroke severity and age) analyses were performed using random effects methodology. Results: We included 8 RCTs (5,332 total patients, 34% with APP). In unadjusted analyses (Figure 1), APP was associated with higher likelihood of sICH (OR=2.01, 95%CI: 1.53-2.63) and death (OR=1.59, 95%CI: 1.24-2.03; 1C) and lower likelihood of 3-month FI (OR=0.69, 0.56-0.85). No association was detected between APP and 3-month FFO (OR=0.79, 95%CI: 0.58-1.07) and CR (OR=0.64, 95%CI: 0.04-11.66). In adjusted analyses (Figure 2), APP was related to higher odds of sICH (OR=1.89, 95%CI: 1.14-3.12). There was no association between APP and 3-month FI (OR=0.94, 95%CI: 0.70-1.26) or death (OR=1.01, 95%CI: 0.55-1.86). In all analyses no evidence of heterogeneity was detected. Conclusion: Despite APP association with a higher risk of sICH after thrombolysis, three-month functional outcomes appear un-affected by APP. APP before IVT should not be used as an excuse to withhold or to lower the dose of IVT.

Admission systolic blood pressure and outcomes in large vessel occlusion strokes treated with endovascular treatment

Background and purposeHigh admission blood pressure (BP) levels have been associated with lower recanalization rates after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) with emergent large vessel...