Intravenous Thrombolysis For Stroke Research Articles

Ultra-Early Intravenous Stroke Thrombolysis

We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

A step closer to statin therapy for stroke?

Accumulating evidence suggests that statin therapy could assist functional recovery following acute ischaemic stroke. A recent study indicates that early administration of statins after intravenous thrombolysis for stroke improves functional outcomes, and reduces mortality and neurological deterioration. Owing to the observational study design, however, these findings should be interpreted cautiously.

Intravenous thrombolytic treatment in the oldest old.

Background and Purpose. Intravenous thrombolysis using tissue plasminogen activator is safe and probably effective in patients >80 years old. Nevertheless, its safety has not been specifically addressed for the oldest old patients (≥85 years old, OO). We assessed the safety and effectiveness of thrombolysis in this group of age. Methods. A prospective registry of patients treated with intravenous thrombolysis. Patients were divided in two groups (<85 years and the OO). Demographic data, stroke aetiology and baseline National Institute Health Stroke Scale (NIHSS) score were recorded. The primary outcome measures were the percentage of symptomatic intracranial haemorrhage (SICH) and functional outcome at 3 months (modified Rankin Scale, mRS). Results. A total of 1,505 patients were registered. 106 patients were OO [median 88, range 85–101]. Female sex, hypertension, elevated blood pressure at admission, cardioembolic strokes and higher basal NIHSS score were more frequent in the OO. SICH transformation rates were similar (3.1% versus 3.7%, P = 1.00). The probability of independence at 3 months (mRS 0–2) was lower in the OO (40.2% versus 58.7%, P = 0.001) but not after adjustment for confounding factors (adjusted OR, 0.82; 95% CI, 0.50 to 1.37; P = 0.455). Three-month mortality was higher in the OO (28.0% versus 11.5%, P < 0.001). Conclusion. Intravenous thrombolysis for stroke in OO patients did not increase the risk of SICH although mortality was higher in this group.

Intravenous Thrombolysis for Stroke Increases Over Time at Primary Stroke Centers

We evaluated the impact that duration as a primary stroke center (PSC) had on tissue-type plasminogen activator (tPA) utilization for acute ischemic stroke. A retrospective analysis of the Illinois Hospital Association CompData was performed identifying those patients with primary discharge diagnosis of acute ischemic stroke based on International Classification of Diseases version 9 codes. We assessed utilization of tPA by International Classification of Diseases version 9 procedure code (99.10). We categorized patients as cared for at non-PSC, PSC >1 year before, ≤1 year before, ≤1 year after, and >1 year after certification. We used generalized estimating equations to calculate adjusted odds ratios for tPA utilization by PSC category. Among 119,539 acute ischemic stroke patients (mean age, 72 years; 55.2% women), tPA use was 1.9% but increased by PSC category (P<0.001): (1) non-PSC 0.9%; (2) >1 year before PSC certification 1.4%; (3) ≤1 year before certification 3.2%; (4) ≤1 year after certification 4.3%; and (5) >1 year after certification 6.5%. Adjusting for age, insurance status, admission source, year of study, region of Illinois, and hospital bed size, the odds of tPA utilization increased with advancing stage of PSC certification (highest category: adjusted odds ratio, 2.37; 95% confidence interval, 1.52-3.71). Although increasing over time, stroke thrombolysis is strongly impacted by the PSC certification process. Rather than waning or stagnating, tPA utilization increases at PSC from the earliest phases of preparation through certification and subsequent maintenance.

Early Recurrent Ischemic Stroke Complicating Intravenous Thrombolysis for Stroke

Mechanisms of early neurologic deterioration after treatment with intravenous, recombinant, tissue-type plasminogen activator (IV rt-PA) include symptomatic intracerebral hemorrhage (SICH) and early recurrent ischemic stroke. We observed a number of cases of acute deterioration due to recurrent ischemic events. We undertook a single-center, retrospective analysis of consecutive acute stroke patients treated with IV rt-PA between January 2006 and December 2008 to define the incidence of early neurologic deterioration (>or=4-point drop on the National Institutes of Health Stroke Scale within 72 hours) and its mechanism. Deterioration was attributed to SICH when associated with a PH1 or PH2 hemorrhage on postdeterioration computed tomography scans, to recurrent ischemic stroke when there was clinical and radiologic evidence of a new territorial infarction or new vessel occlusion, and otherwise to evolution of the incident stroke. Of 228 consecutive IV rt-PA-treated patients, 34 (15%) developed early neurologic deterioration, 18 (8%) secondary to incident strokes 10 (4.4%) due to SICH, and 6 (2.6%) due to early recurrent ischemic events, which were significantly associated with atrial fibrillation (present in 5 of 6 patients; 4 paroxysmal, 1 permanent). In 4 patients, sudden clinical deterioration developed during or shortly after IV rt-PA infusion, and in 2, deterioration developed 3 days later. All died 2 days to 2 weeks later. The single case without atrial fibrillation had a recurrent, contralateral, middle cerebral artery stroke during IV rt-PA infusion and multiple high-signal emboli detected by transcranial Doppler. Early recurrent ischemic stroke accounted for 5 of 12 (42%) cases of early neurologic deterioration in patients with atrial fibrillation. In this single-center series, the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous atrial fibrillation.

Response to Comments on: “Early Carotid Endarterectomy after Intravenous Thrombolysis for Acute Ischemic Stroke”

We appreciate the opportunity to respond to the thoughtful letter from Rashid et al. concerning our article “Early Carotid Endarterectomy after Intravenous Thrombolysis for Acute Ischemic Stroke”. Concerning the timing of carotid endarterectomy (CEA) after intra venous thrombolysis (IVT) we based our policy mainly on the reanalysis of NASCET and ECST results in 2004.1Rothwell P.M. Eliasziw M. Gutnikov S.A. Warlow C.P. Barnett H.J. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.Lancet. 2004; 363: 915-924Google Scholar For neurological stable individuals, the authors demonstrated clearly that surgery provide the highest benefit over medical management when CEA is performed within the first two weeks after the patient's last symptoms. In our opinion IVT may not change so much the natural history of atheromatous symptomatic carotid stenosis. Additionally, it has been also reported that the presence of a severe ipsilateral carotid stenosis was associated with poor clinical outcome after IVT and it might be recommended to adopt for those specific patients an aggressive reperfusion strategy.2Rubiera M. Alvarez-Sabin J. Ribo M. Montaner J. Santamarina E. Arenillas J.F. et al.Predictors of early arterial reocclusion after tissue plasminogen activator-induced recanalization in acute ischemic stroke.Stroke. 2005; 36: 1452-1456Google Scholar, 3Molina C.A. Montaner J. Arenillas J.F. Ribo M. Rubiera M. Alvarez-Sabin J. Differential pattern of tissue plasminogen activator-induced proximal middle cerebral artery recanalization among stroke subtypes.Stroke. 2004; 35: 486-490Google Scholar Finally, in our experience nine out of twelve patients had a remaining carotid stenosis ≥90% after IVT. Restoring quickly a normal blood flow in a freshly recanalized vessel may prevent reocclusion and allow us to verticalize the patient maintained strictly supine until surgery to avoid any worsening of the symptoms due to cerebral hypoperfusion. Therefore, we recommend performing surgery after IVT as soon as possible following our strict criteria of operability which are more numerous compared to those applied by Rashid et al. We agree that actually literature evidence remains extremely poor on this subject, and we may probably never have randomized control trials comparing immediate versus delayed CEA after IVT for stroke. However, we believe that in the near future we will observe in the literature some short series from high volume centers and meta analysis of them may provide sensible evidence base on the stroke and death rate that might be expected in such situation to provide better information to the patient. Comment on “Early Carotid Endarterectomy after Intravenous Thrombolysis for Acute Ischaemic Stroke, Bartolia MA et al. May 2009”European Journal of Vascular and Endovascular SurgeryVol. 38Issue 4PreviewWe read the article with great interest. The timing of carotid endarterectomy (CEA) post thrombolysis is an area requiring further evidence. Bartolia et al. found that performing early CEA in patients post thrombolysis could reduce the risk of recurrent stroke. The sample of 12 patients yielded a stroke and death rate of 8.3%.1 Full-Text PDF Open Archive

Site of Arterial Occlusion Identified by Transcranial Doppler Predicts the Response to Intravenous Thrombolysis for Stroke

The objective of this study was to examine clinical outcomes and recanalization rates in a multicenter cohort of stroke patients receiving intravenous tissue plasminogen activator by site of occlusion localized with bedside transcranial Doppler. Angiographic studies with intraarterial thrombolysis suggest more proximal occlusions carry greater thrombus burden and benefit less from local therapy. Using validated transcranial Doppler criteria for specific arterial occlusion (Thrombolysis in Brain Ischemia flow grades), we compared the rate of dramatic recovery (National Institutes of Health Stroke Scale score < or =2 at 24 hours) and favorable outcomes at 3 months (modified Rankin Scale < or =1) for each occlusion site. We determined the likelihood of recanalization at various occlusion sites and its predictors. Then, stepwise logistic regression was used to determine predictors of complete recanalization. Three hundred thirty-five patients had a mean age 69+/-13 years and 48.5% were women (median baseline National Institutes of Health Stroke Scale score 16 [range, 3 to 32], mean time to transcranial Doppler 140+/-84 minutes, and mean time to intravenous tissue plasminogen activator 145+/-68 minutes). Distal middle cerebral artery occlusion had an OR of 2 for complete recanalization (50 of 113 [44.2%], 95% CI: 1.1 to 3.1, P=0.005), proximal middle cerebral artery 0.7 (49 of 163 [30%], 95% CI: 0.4 to 1.1, P=0.13), terminal internal carotid artery 0.1 (one of 17 [5.9%], 95% CI: 0.015 to 0.8, P=0.015), tandem cervical internal carotid artery/middle cerebral artery 0.7 (6 of 22 [27%], 95% CI: 0.3 to 1.9, P=0.5), and basilar artery 0.96 (3 of 10 [30%], 95% CI: 0.2 to 4, P=0.9). Prerecombinant tissue plasminogen activator National Institutes of Health Stroke Scale score, systolic blood pressure, glucose, and Thrombolysis in Brain Ischemia flow grade at the occlusion site were the negative independent predictors for complete recanalization in the final model. There were no associations among time to treatment, stroke mechanisms, or recanalization rate. Patients with no flow (Thrombolysis in Brain Ischemia 0) at the occlusion site had less probability of complete recanalization than patients with dampened flow (Thrombolysis in Brain Ischemia 3) (OR(adj): 0.256, 95% CI: 0.11 to 0.595, P=0.002). Continuous transcranial Doppler monitoring (exposure to ultrasound) was a positive predictor for complete recanalization (OR(adj): 3.02, 95% CI: 1.396 to 6.514, P=0.005). National Institutes of Health Stroke Scale score < or =2 at 24 hours was achieved in 66 of 305 patients (22%): distal middle cerebral artery 33% (35 of 107), tandem cervical internal carotid artery/middle cerebral artery 24% (5 of 21), proximal middle cerebral artery 16% (24 of 155), basilar artery 25% (2 of 8), and none of the patients with terminal internal carotid artery had dramatic recovery (0%, n=14; P=0.003). Modified Rankin Scale score < or =1 was achieved in 90 of 260 patients (35%): distal middle cerebral artery 52% (50 of 96), proximal middle cerebral artery 25% (33 of 131), tandem cervical internal carotid artery/middle cerebral artery 21% (3 of 14), terminal internal carotid artery 18% (2 of 11), and basilar artery 25% (2 of 8) (P<0.001). Patients with distal middle cerebral artery occlusion were twice as likely to have a good long-term outcome as patients with proximal middle cerebral artery (OR: 2.1, 95% CI: 1.1 to 4, P=0.025). Clinical response to thrombolysis is influenced by the site of occlusion. Patients with no detectable residual flow signals as well as those with terminal internal carotid artery occlusions are least likely to respond early or long term.

Temporal Profile of Recanalization After Intravenous Tissue Plasminogen Activator

Intravenous thrombolysis in stroke achieves arterial recanalization in approximately 50% of cases. Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)-treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17. Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), and none for 84 (47%). Although early flow improvement was observed in up to 45% of patients, only 19% of patients with persistent occlusion (11% of total) presented delayed recanalization (odds ratio [OR] delayed/early recanalization, 0.16; 95% CI, 0.085 to 0.304; P<0.001). Among patients with persistent occlusion at 2 hours, only 13 (7% of total) presented late flow improvement (OR late/early recanalization, 0.09; 95% CI, 0.043 to 0.196; P<0.001). The few patients with late recanalization presented comparable median 48-hour NIHSS to those with early/delayed recanalization (3 versus 4.5; P=0.9) and much lower than those with persistent occlusion after 6 hours (3 versus 15; P=0.005). At 3 months, the rate of mRS < or =2 was not statistically different between patients with early/delayed versus late recanalization (55% versus 86%; P=0.12) but was lower if occlusion persisted 6 hours after onset (22%; P<0.001). The majority of t-PA-induced recanalizations occur during the first hour after treatment. Recanalizations during the following hours are rare but still related to clinical improvement if achieved within 6 hours from onset. Rescue reperfusion techniques should be considered if flow improvement is not observed 60 minutes after t-PA bolus.