Pere Cardona

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.

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.

Trevo versus solitaire a head-to-head comparison between two heavy weights of clot retrieval.

Recent reports have indicated that mechanical thrombectomy may have potential to treat acute ischemic stroke. However, few comparative studies of neurothrombectomy devices are reported. This study aims to compare the safety and effectiveness of two retrievable stent systems in acute ischemic stroke patients.

Trevo System: Single‐Center Experience with a Novel Mechanical Thrombectomy Device

Recent reports have indicated that mechanical thrombectomy may have the potential to treat acute ischemic stroke. This study aims to describe the safety and effectiveness of Trevo Retriever, using Stentriever technology, in revascularization of patients with acute ischemic stroke.

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.

Recurrent transient ischaemic attack and early risk of stroke: data from the PROMAPA study

Background Many guidelines recommend urgent intervention for patients with two or more transient ischaemic attacks (TIAs) within 7 days (multiple TIAs) to reduce the early risk of stroke. Objective To determine whether all patients with multiple TIAs have the same high early risk of stroke. Methods Between April 2008 and December 2009, we included 1255 consecutive patients with a TIA from 30 Spanish stroke centres (PROMAPA study). We prospectively recorded clinical characteristics. We also determined the short-term risk of stroke (at 7 and 90 days). Aetiology was categorised using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Results Clinical variables and extracranial vascular imaging were available and assessed in 1137/1255 (90.6%) patients. 7-Day and 90-day stroke risk were 2.6% and 3.8%, respectively. Large-artery atherosclerosis (LAA) was confirmed in 190 (16.7%) patients. Multiple TIAs were seen in 274 (24.1%) patients. Duration <1 h (OR=2.97, 95% CI 2.20 to 4.01, p<0.001), LAA (OR=1.92, 95% CI 1.35 to 2.72, p<0.001) and motor weakness (OR=1.37, 95% CI 1.03 to 1.81, p=0.031) were independent predictors of multiple TIAs. The subsequent risk of stroke in these patients at 7 and 90 days was significantly higher than the risk after a single TIA (5.9% vs 1.5%, p<0.001 and 6.8% vs 3.0%, respectively). In the logistic regression model, among patients with multiple TIAs, no variables remained as independent predictors of stroke recurrence. Conclusions According to our results, multiple TIAs within 7 days are associated with a greater subsequent risk of stroke than after a single TIA. Nevertheless, we found no independent predictor of stroke recurrence among these patients.

Access to Endovascular Treatment in Remote Areas

Background and Purpose— Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. Methods— We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. Results— Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245–435]) and 120 minutes longer in group C (350 minutes [284–408]) compared with group A (230 minutes [160–407]; P<0.001). Conclusions— Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.