XVII. European Stroke Conference
Nice, France

Oral Session:

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 8:30 - 8:40 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

01
Relationship of blood pressure and antihypertensive therapy with outcomes in acute ischemic stroke treated with intravenous thrombolysis: Results from SITS-ISTR
N. Ahmed    N.G.Wahlgren    M. Brainin    J. Castillo    G.A.Ford    M. Kaste    D. Toni                     
SITS-ISTR collaborators

Karolinska University Hospital, Karolinska Institutet

SWEDEN

Background: The optimal management of blood pressure (BP) in acute stroke remains unclear. For ischemic stroke treated with intravenous thrombolysis current guidelines suggest pharmacological intervention if systolic blood pressure (SBP) exceeds 180 mm Hg. We determined the relationship of BP and antihypertensive therapy with clinical outcomes following stroke-thrombolysis. Methods: The Safe Implementation of Treatment in Stroke (SITS) International Stroke Thrombolysis Register (ISTR) prospectively recorded 10581 treatments between 2002 and 2006. BP values were recorded at baseline, 2h and 24h after thrombolysis. Known hypertensive was defined by either history of hypertension or treated with antihypertensive at admission. Known hypertensives and others were categorized by antihypertensive therapy following thrombolysis within 7days: 1. Hypertensive treated with antihypertensive (n=5366), 2. Hypertensive not treated with antihypertensive (n=1501), 3. New antihypertensive in others (n=963), 4. No antihypertensive in non hypertensive (n=2493). Outcomes were symptomatic intracerebral haemorrhage (SICH), mortality and independence at 3 months. Results: In multivariable analysis, high SBP following thrombolysis was associated with a worse outcome (p<0.001). Categorized SBP had a linear association with SICH but U shaped relationship to mortality and independence with SBP 141-150 mm Hg associated with the best outcomes. Adjusted odds ratio (95% CI) for mortality for groups 1-3 versus group 4 were: 0.82 (0.73-0.92), 1.63 (1.42-1.87), 0.63 (0.51- 0.79) respectively and for independence was 1.03 (0.95- 1.12), 0.88 (0.79-0.98), 1.09 (0.96-1.25). Conclusions: These results suggest a more active BP lowering approach in moderate hypertension is indicated early after intravenous thrombolysis. In particular, not providing antihypertensive therapy in known hypertensives was associated with worse outcome and initiation of new antihypertensive therapy in moderate hypertension seemed to have a favourable outcome.

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 8:40 - 8:50 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

02
Is it time to reassess the SITS-MOST criteria for thrombolysis?
M. Rubiera    M. Ribo    O. Maisterra    R. Delgado-Mederos    E. Santamarina    G. Ortega    L. Dinia    J. Alvarez-Sabin    C.A.Molina       
 

Vall d'Hebron Hospital. Barcelona

SPAIN

Background: The SITS-MOST guidelines establish some criteria to increase safety in acute stroke thrombolysis. However, they preclude treatment in an important proportion of patients. We aimed to assess safety and efficacy of thrombolysis in patients with SITS-MOST exclusion criteria. Patients and Methods: Three-hundred and seventy acute-stroke iv tPA-treated patients from our prospective database were studied. Patients were classified as SITS-MOST (SM) or non-SITS-MOST (NSM) according to the fulfilling of SITS-MOST criteria. Presence and location of arterial occlusion and recanalization (RE) was assessed by TCD. Clinical evaluation was asses by NIHSS score at baseline and after 24h. mRS score was used to evaluate 3-months outcome. Functional independency was considered if mRS≤2. Results: Median admission NIHSS was 17. One hundred and seventy (45.8%) patients were SM and 200 (54.1%) NSM. Among NSM patients, 91 (45.5%) were >80y, 124 (63.6%) were treated after 3h from stroke onset, 16 (8.2%) were taken anticoagulants and 12 (6.1%) had history of DM plus previous stroke. NSM patients were more frequently women, hypertensive with cardioembolic stroke. Stroke severity and clot location were similar in both groups. RE rate after 2h (47.6%/50.3%, p=0.36) and clinical improvement (NIHSS decrease ≥4 points) at 24h (49.5% / 55.6%, p=0.114) were comparable in SM and NSM groups (p=0.36), as well as the symptomatic intracranial haemorrhage rate (4.8%/4.1%, p=0.478). However, in-hospital mortality tended to be higher in NSM (10.5%/16.1%, p=0.084) and independence at 3 months was more frequently achieved in SM patients (48.7%/36.4%, p=0.019). No differences were found when patients >80y were excluded from the NSM group. Conclusion: More than one-third of patients not fulfilling SITS-MOST criteria benefit from tPA treatment. Extension of SITS-MOST criteria should be considered in future studies.

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 8:50 - 9:00 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

03
Thrombolysis in young patients: the SITS-MOST data.
A. Anzini    A. Niaz    L. Durastanti    N. Wahlgren    M. Prencipe    D. Toni                            
 

Unità di Trattamento Neurovascolare Università La Sapienza Rome Italy

ITALY

Background and purposes: data from the NINDS t-PA trial show that younger patients benefit more from thrombolytic treatment than older ones when adjusted for stroke severity. Aim of this study is to compare the response to i.v. thrombolysis of patients aged 18 to 45 years to that of older ones, who were treated in Safe Implementation of Trombolysis in Stroke Monitoring Study (SITS-MOST). Subjects and Methods: Clinical and radiological data of patients were collected before treatment and in acute and 3 month follow-up. In SITS-MOST, primary outcome measures were symptomatic intracerebral haemorrhage (SICH) and 3-month mortality rate. A secondary outcome was functional independence at 3 months (modified Rankin score 0-2). Additional outcome measures were SICH according to Cochrane/NINDS definition and ECASS criteria and a complete recovery (mRS 0-1) at 3 months. Results : Of 6483 patients, 412 (6,4%) were aged ≤ 45 and 6071 (93,6%) were over 45. Median baseline NIHSS score did not differ between the two age subgroups. At the univariate analysis, age ≤ 45 is significantly associated with a decreased rate of SICH, according to Cochrane/NINDS definition (4,1% vs 7,5%; p < 0.001) and a lower 3-month mortality rate (5,5% vs 11,7%; p < 0.001). Cerebral infarction was the most common cause of death (77,3%) in the younger patients. Functional independence was reported in 76 % and 53 % of patients in the two age subgroups (p < 0,001), while a complete recovery was observed respectively in 54 % and in 38 % of patients (p < 0,001). Conclusions: Our data confirm that outcomes are better in young ischemic stroke patients compared to older ones after treatment with intravenous t-PA. However, a more detailed critical analysis of indicators that might predict outcome and/or different response to intravenous thrombolysis between the two age subgroups is warranted.

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 9:00 - 9:10 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

04
Differences in stroke outcome after thrombolysis depending on age.
M. Alonso de Leciñana    M.  Luque    P.  Simal    J.A. Egido    B.  Fuentes    E.  Díez Tejedot    F.  Díaz Otero    A.  Gil    J.  Masjuan       
 

University Hosp. Ramón y Cajal(1),Clinico San Carlos(2),La Paz(3),Gregorio Marañón(4).Madrid

SPAIN

AIMS: To determine whether age might condition differences in management and outcome of tPA treated patients. METHODS: Prospective multicenter observational study including consecutive acute stroke patients treated with intravenous tPA. Patients were divided in <50 years, 50-75 and >75. Additionally patients over 80 were compared with the rest. Baseline characteristics, risk factors, aetiology, stroke severity (NIHSS) and time-to-treatment were recorded. Stroke outcome (mRS at 3 months) intra-cranial symptomatic haemorrhage (SICH) and mortality were compared between groups. RESULTS: From Jan-04 to Nov-07 412 patients were registered (median age 70, range: 21-89, 54% males). Hypertension and atrial fibrillation were more prevalent among >75 and tobacco smoking among < 50. Unusual and undetermined strokes were more frequent in <50 and other aetiologies in older patients. Older patients suffered more severe strokes [NIHSS median (interquartile range): < 50: 12 (7-16), 50-70: 14(9-18) > 75: 14(9-19), p=0.055; >80: 16.50(11.25-22.5), p=0.026]. Probability of independence at three months (mRs 0-2) decreases with age (< 50: 71%, 50-70: 57%; > 75: 48%, p=0.035; >80: 33 %, p=ns) while mortality increases (< 50: 4%, 50-70: 13%; > 75: 23%, p=0.006; >80: 38%, p=0.013). There are no differences regarding SICH (< 50: 2%, 50-70: 6%; > 75: 2%, >80: 0%) CONCLUSIONS: Older patients present more severe strokes and worse outcome after tPA. However, SICH rate is not increased in these patients. Youngest patients present different risk factors and aetiologies, suffer less severe strokes and have greater probability of independence.

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 9:10 - 9:20 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

05
Timing of microbubble-enhanced sonothrombolysis strongly predicts intracranial hemorrhage in acute ischemic stroke
L. Dinia    M. Rubiera    M. Ribo    E. Santamarina    O. Maisterra    R. Delgado-Mederos    J. Alvarez-Sabin    J. Montaner    C. Molina       
 

Hospital Vall D'Hebron Barcelona

SPAIN

Background. Although ultrasound-activated microbubbles (MB) accelerates clot lysis, MB activation has shown to promote blood barrier disruption. We conducted a case-control study aimed to investigate the risk of HT after MB-enhanced sonothrombolysis in acute stroke. Patients and Methods We prospectively evaluated 188 patients with acute stroke related to MCA occlusion and treated with i.v. tPA < 6 h of stroke onset. Patients received continuous 2-hour TCD monitoring plus 3 doses of 2.5 g of Levovist given at 2, 20, and 40 min after tPA bolus (MB group). These patients were compared with 98 historical stroke patients treated with tPA plus 2-hour TCD monitoring (control group). Presence and extent of HT on 24-h CT was blinded assessed as HI1,HI2, PH1 and PH2. Results: Median baseline NIHSS was 17. On TCD, 69.6% patients had a proximal and 30.4% a distal MCA occlusion. Recanalization rates at 1h (32.2% vs 21%) , 2h (50.0% vs 36.7%), 6 h (63.8%/44.5%) and 12 h (74.3%/56.2%) were significantly higher in the MB compared to the control group (p<0.05). MB administration was significantly associated with an increased risk of HI1-H2 (21% vs 12%, p=0.026 OR 5.8 95% IC 2.1-65), and higher degree of clinical improvement at 24 h (54.9% / 31.1%, p=0.004). PH1-PH2 (3.3% vs 3.8%; p=0.8) and symptomatic ICH rates (2.9% / 2.1%, p=0.580) were comparable in both groups. Moreover, the extend of bleeding after MB-enhanced sonothrombolysis was linked to the time-to-reperfusion. Early (<6h) recanalization independently predicted HI in the MB group (OR 6.3 95% IC 2.3-56) but not in the control group. Delayed (>6h) or no recanalization (>6h) was significantly associated with PH1-PH2 in both MB (p= 0.024) and control group (p= 0.045), respectively. Conclusion: The extend of bleeding after MB-enhanced sonothrombolysis is linked to the time-to-reperfusion. MB administration is associated with early recanalization and high rate of HI1-HI2, but it does not increase the risk of symptomatic ICH.

Acute stroke: treatment concepts I
Date: Wednesday 14 May 2008  
Time: 9:20 - 9:30 -  Room: Clio/Thalie
Chair: W.D. Heiss, Germany and P. Trouillas, France

06
Symptomatic Intracerebral Haemorrhage, Mortality and Independence at 3 months for patients treated 3-4 ½ h after stroke onset in the SITS Thrombolysis Register (SITS-ISTR)
N. Wahlgren    N. Ahmed    A. Davalos    W. Hacke    K.R.Lees                                   
SITS collaborators

Karolinska University Hospital

SWEDEN

Background: Thrombolysis using rt-PA is approved in ischaemic stroke within 3 h of symptoms onset but evidence from randomised controlled trials (RCT) suggests a benefit until 4.5 h. The ECASS 3 study is evaluating the effect of rt-PA in the 3 to 4.5 h interval. The Safe Implementation of Treatment in Stroke (SITS) International Stroke Thrombolysis Register (ISTR) is a prospective internet based audit of thrombolysis in ischaemic stroke. We determined the outcome in patients treated intravenously within 3-4.5 h and compared the results with patients treated within 3h. Methods: 11865 of 16047 patients recorded in SITS-ISTR until November 15, 2007, were treated within 3h and 664 between 3 to 4.5h, all otherwise fulfilling European summary of product characteristics (SPC) criteria. Our main outcomes were: symptomatic intracerebral haemorrhage (SICH) per SITS-MOST (Monitoring Study), defined as NIHSS deterioration ≥4 within 24h with type 2 intracerebral haemorrhage, SICH per RCT, defined as NIHSS deterioration ≥1 within 7 days with any haemorrhage, mortality, and independency as defined by modified Rankin Score (mRS) of 0-2 at 3 months. Results: Results are median (IQR) or proportions (%) comparing 3 to 4.5h vs. within 3h cohort. Stroke onset to treatment time (OTT) was 195 (187-210) vs. 140 (115-165) minutes, age 65 (55-73) vs. 68 (58-74) years, baseline NIHSS 11 (7-16) vs. 12 (8-17). There were no statistically significant differences in other baseline and demographic data except for hyperlipidemia 30.3 vs. 34.7%, p= 0.03, signs of current infarction on baseline imaging (31.3 vs.21.5%, p<0.05). The rate of SICH per SITS-MOST definition was 2.2% vs. 1.6% (p=0.24), SICH per RCT definition was 8.0% vs. 7.3% (p=0.46), mortality 12.7% vs. 12.2% (p=0.72) and Independence 58.0% vs. 56.3% (p=0.42). Conclusions: These results support the extended time window for thrombolysis up to 4.5h in acute ischaemic stroke provided treatment is given according to the European SPC/ SITS-MOST criteria. A final conclusion will depend on the outcome of ECASS 3.