Alejandro Tomasello

Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke

BACKGROUND We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).

Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. OBJECTIVE To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. DESIGN, SETTING, AND PATIENTS Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. EXPOSURES Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. MAIN OUTCOMES AND MEASURES The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. RESULTS Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%]). CONCLUSIONS AND RELEVANCE In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.

Single-Center Experience of Cerebral Artery Thrombectomy Using the TREVO Device in 60 Patients With Acute Ischemic Stroke

Background and Purpose— We sought to explore the safety and efficacy of the new TREVO stent-like retriever in consecutive patients with acute stroke. Methods— We conducted a prospective, single-center study of 60 patients (mean age, 71.3 years; male 47%) with stroke lasting <8 hours in the anterior circulation (n=54) or <12 hours in the vertebrobasilar circulation (n=6) treated if CT perfusion/CT angiography confirmed a large artery occlusion, ruled out a malignant profile, or showed target mismatch if symptoms >4.5 hours. Successful recanalization (Thrombolysis In Cerebral Infarction 2b–3), good outcome (modified Rankin Scale score 0–2) and mortality at Day 90, device-related complications, and symptomatic hemorrhage (parenchymal hematoma Type 1 or parenchymal hematoma Type 2 and National Institutes of Health Stroke Scale score increment ≥4 points) were prospectively assessed. Results— Median (interquartile range) National Institutes of Health Stroke Scale score on admission was 18 (12–22). The median (interquartile range) time from stroke onset to groin puncture was 210 (173–296) minutes. Successful revascularization was obtained in 44 (73.3%) of the cases when only the TREVO device was used and in 52 (86.7%) when other devices or additional intra-arterial tissue-type plasminogen activator were also required. The median time (interquartile range) of the procedure was 80 (45–114) minutes. Good outcome was achieved in 27 (45%) of the patients and the mortality rate was 28.3%. Seven patients (11.7%) presented a symptomatic intracranial hemorrhage. No other major complications were detected. Conclusions— The TREVO device was reasonably safe and effective in patients with severe stroke. These results support further investigation of the TREVO device in multicentric registries and randomized clinical trials.

Hemodynamic Response-Guided Therapy for Prevention of Variceal Rebleeding: An Uncontrolled Pilot Study

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open‐labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (≥20% decrease in HVPG from baseline) were maintained on drugs, partial responders (≥10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal‐systemic shunt (TIPS). Mean follow‐up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis. (HEPATOLOGY 2006;44:806–812.)

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

Background and Purpose— We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. Methods— We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ⩽ or >80 years; onset-to-groin puncture ⩽ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ⩽2) and mortality at 3 months by multivariate modeling. Results— We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ⩽6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. Conclusions— This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion

Background and Purpose— A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. Methods— We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0–2) was described via adjusted odds ratios (ORs) for every 30-minute delay. Results— Median admission National Institutes of Health Stroke Scale was 17.0 (14.0–20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59–0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67–1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54–0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35–0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68–1.44). Conclusions— Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience

Background Patients with M2 middle cerebral artery (MCA) occlusions are not always considered for endovascular treatment. Objective To study outcomes in patients with M2 occlusion treated with endovascular procedures in the era of stentrievers. Methods We studied patients prospectively included in the SONIIA registry (years 2011–2012)—a mandatory, externally audited registry that monitors the quality of reperfusion therapies in Catalonia in routine practice. Good recanalization was defined as postprocedure Thrombolysis in Cerebral Infarction (TICI) score 2b–3; dramatic recovery as drop in National Institutes of Health Stroke Scale (NIHSS) score >10 points or NIHSS score <2 at 24–36 h; and good outcome as modified Rankin score (mRS) 0–2 at 3 months. A 24 h CT scan determined symptomatic intracranial hemorrhage (SICH) and infarct volume. Results Of 571 patients who received endovascular treatment, 65 (11.4%) presented an M2 occlusion on initial angiogram, preprocedure NIHSS 16 (IQR 6). Mean time from symptom onset to groin puncture was 289±195 min. According to interventionalist preferences 86.2% (n=56) were treated with stentrievers (n=7 in combination with intra-arterial tissue plasminogen activator (tPA), 4.6% (n=3) received intra-arterial tPA only, and 9.2% (n=6) diagnostic angiography only. Good recanalization (78.5%) was associated with dramatic improvement (48% vs 14.8%; p=0.02), smaller infarct volumes (8 vs 82 cc; p=0.01) and better outcome (mRS 0–2: 66.3% vs 30%; p=0.03). SICH (9%) was not associated with treatment modality or device used. After adjusting for age and preprocedure NIHSS, good recanalization emerged as an independent predictor of dramatic improvement (OR=5.9 (95% CI 1.2 to 29.2), p=0.03). Independent predictors of good outcome at 3 months were age ( OR=1.067 (95% CI 1.005 to 1132), p=0.03) and baseline NIHSS ( OR=1.162 (95% CI 1.041 to 1.297), p<0.01). Conclusions Endovascular treatment of M2 MCA occlusion with stentrievers seems safe. Induced recanalization may double the chances of achieving a favorable outcome, especially for patients with moderate or severe deficit.

Age-adjusted infarct volume threshold for good outcome after endovascular treatment

Background and purpose Infarct volume and age are strong predictors of outcome in patients with stroke. We aimed to determine the impact of infarct volume on outcome according to age. Methods Consecutive patients with acute stroke with documented internal carotid artery/middle cerebral artery occlusion who underwent endovascular procedures were studied. Patients were categorized in three age groups: <70 years (G1), 70–79 years (G2), ≥80 years (G3). The Alberta Stroke Program Early CT score (ASPECTS) was graded on initial CT. Time of successful recanalization (Thrombolysis In Cerebral Infarct (TICI) ≥2b )and good outcome at 3 months (modified Rankin Scale score ≤2) were recorded. Infarct volume was measured on the 24 h control CT. Results A total of 214 patients were studied (G1: 68; G2: 74; G3: 72). For all patients the mean infarct volume was 94.7±127 mL; 35.6% had a good outcome. We observed larger infarct volumes in patients with a bad outcome in each age group (G1: 22 vs 182 mL, p<0.01/G2: 22 vs 164 mL, p<0.01/G3: 7.6 vs 132 mL, p<0.01). However, the target cut-off infarct volume that better predicted a good outcome decreased as age increased: G1: 49 mL (sensitivity 80%, specificity 92.6%); G2: 32.5 mL (sensitivity 80%, specificity 81%); G3: 15.2 mL (sensitivity 81.3%, specificity 86.7%). Overall, after adjusting for age, occlusion location, baseline NIH Stroke Scale score and infarct volume, the only predictor of a good outcome was achieving a final infarct volume less than the age-adjusted target (OR 5.5, 95% CI 1.6 to 18.8; p<0.01). The probability of achieving an infarct volume less than the age-adjusted target decreased according to baseline ASPECTS, time and degree of recanalization. Conclusions Age-adjusted infarct size might represent a powerful surrogate marker of stroke outcome and further refine the predictive accuracy of infarct volume on prognosis in patients with stroke undergoing endovascular treatment. This information may be used in the design of new trials to individualize selection criteria for different age groups.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different

Background and Purpose— Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. Methods— Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel–Haenszel test statistic. Results— We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74–1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74–1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25–1.27). Conclusions— This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

Mechanical Thrombectomy in and Outside the REVASCAT Trial: Insights From a Concurrent Population-Based Stroke Registry.

Background and Purpose— Recent trials have shown the superiority of endovascular thrombectomy (EVT) over medical therapy alone in certain stroke patients with proximal arterial occlusion. Using data from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within 8-Hours of Symptom Onset (REVASCAT) and a parallel reperfusion treatment registry, we sought to assess the utilization of EVT in a defined patient population, comparing the outcomes of patients treated in and outside the REVASCAT trial. Methods— SONIIA [Sistema Online d’Informació de l’Ictus Agut], a population-based, government-mandated, prospective registry of reperfusion therapies for stroke encompassing the entire population of Catalonia, was used as data source. The registry documents 5 key inclusion criteria of the REVASCAT trial: age, stroke severity, time to treatment, baseline functional status, and occlusion site. We compared procedural, safety, and functional outcomes in patients treated inside and outside the trial. Results— From November 2012 to December 2014, out of 17596 ischemic stroke patients in Catalonia (population 7.5 million), 2576 patients received reperfusion therapies (17/100000 inhabitants-year), mainly intravenous thrombolysis only (2036). From the remaining 540 treated with EVT, 103 patients (out of 206 randomized) were treated within REVASCAT and 437 outside the trial. Of these, 399 did not fulfill some of the study criteria, and 38 were trial candidates (8 treated at REVASCAT centers and 30 at 2 non-REVASCAT centers). The majority of procedural, safety, and functional outcomes were similar in patients treated with EVT within and outside REVASCAT. Conclusions— REVASCAT enrolled nearly all eligible patients representing one third of all patients treated with EVT. Patients treated with EVT within and outside REVASCAT had similar outcomes, reinforcing the therapeutic value of EVT. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.