Visnja Padjen

Safety of Thrombolysis in Stroke Mimics Results From a Multicenter Cohort Study

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods— In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results— One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions— In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

IV thrombolysis and renal function

Objective: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT). Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3–6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group. Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m2). A GFR decrease by 10 mL/min/1.73 m2 increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17–1.24]; ORadjusted 1.05 [1.01–1.09]), death (ORunadjusted 1.33 [1.28–1.38]; ORadjusted 1.18 [1.11–1.249]), and sICH (ORunadjusted 1.15 [1.01–1.22]; ORadjusted 1.11 [1.04–1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10–1.58]), death (ORadjusted 1.73 [1.39–2.14]), and sICH (ORadjusted 1.64 [1.21–2.23]) compared with normal GFR (60–120 mL/min/1.73 m2). Low GFR (ORadjusted 1.64 [1.21–2.23]) and stroke severity (ORadjusted 1.05 [1.03–1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41–2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63–0.94]). Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m2 seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Recanalization Therapies in Acute Ischemic Stroke Patients: Impact of Prior Treatment with Novel Oral Anticoagulants on Bleeding Complications and Outcome - A Pilot Study

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Sex Differences and Functional Outcome After Intravenous Thrombolysis

Background and Purpose— Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)–treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care. Methods— Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months. Results— In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02–1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73–1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70–0.99). Conclusions— In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age.

Long-Term Prognosis in Ischemic Stroke Patients Treated with Intravenous Thrombolytic Therapy

BACKGROUND AND PURPOSE It remains unclear if intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator has an impact on the survival and maintenance of a favorable effect on functional recovery over a long follow-up period. The aim of this study was to assess whether or not IVT treatment has a favorable effect on functional recovery and survival less than 1 year after a stroke. METHODS This matched cohort study included 259 patients with acute ischemic stroke (IS) who were treated with IVT and standard care and 259 patients treated with standard care alone in the stroke unit between February 2006 and January 2013. RESULTS After a median follow-up period of 3 years (range, 1-7 years), survival did not differ significantly between the groups; specifically, 56 patients (21.6%) in the thrombolysed group died versus 62 patients (23.94%) in the nonthrombolysed group (log-rank, .240, P = .624). Based on a multivariate Cox proportional hazards regression model, older age (>70 years), stroke severity (National Institutes of Health Stroke Scale score ≥ 15), diabetes mellitus, and a history of atrial fibrillation were independent predictors of long-term mortality after stroke. After the follow-up period, 144 patients (55.6%) in the IVT-treated group versus 112 patients (43.2%) in the control group had an excellent outcome, with a modified Rankin Scale score of 0-1 (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.16-2.32). Based on a multivariate Cox proportional hazards regression model, an excellent 3-month functional recovery was a strong predictor of favorable outcome (HR = 11.27, 95% CI = 6.45-19.63). CONCLUSION The results suggest that IVT for acute IS has a favorable effect on functional recovery more than 1 year after stroke.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis

Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined.

Return to Paid Work after Ischemic Stroke in Patients Treated with Intravenous Thrombolysis

Background: There are no available data confirming the efficacy of intravenous thrombolytic (IVT) treatment on the return to work as one of important outcome measure after acute ischemic stroke (IS). The aim of this study was to analyze the influence of IVT treatment on the return to work after stroke. Methods: This matched cohort study included 279 patients with acute IS (146 treated with IVT and 133 matched patients without IVT) admitted to the Stroke Unit between 2007 and 2013. All patients were working in paid employment immediately before stroke onset. The main outcome measure was return to full-time paid work during follow-up period. Results: After a median follow-up period of 3 years (range 1-7 years), the prevalence of stroke survivors returning to paid work was 42.1% in the IVT group and 33.3% in the non-IVT group (hazard ratio 1.28, 95% CI 0.86-1.91), and IVT treatment was associated with a higher chance of returning to full-time jobs (OR 2.07, 95% CI 1.21-3.51). After adjustment for possible variables, IVT was an independent predictor of returning to full-time jobs. Conclusion: IVT treatment was a positive predictor of returning to full-time work after stroke.

Long-term medication persistence in stroke patients treated with intravenous thrombolysis

OBJECTIVE There are no data regarding long-term medication persistence in stroke survivors treated with intravenous thrombolysis (IVT), which is one of the most important determinants of treatment success. Our objective was to determine long-term medication persistence in stroke patients treated with IVT. METHODS This retrospective observational study included 203 IVT-treated and 197 non-IVT treated patients with acute ischemic strokes (IS) admitted to the Stroke Unit between January 2007 and January 2013. RESULTS During a median follow-up period of 3 years (range 1-7 years), 56 (21.6%) patients in the IVT-group and 62 (23.9%) patients in the non-IVT-group died. There was a higher medication persistence for all secondary stroke prevention medications (anti-thrombotic agents, anti-hypertensive drugs, statins and hypoglycemic drugs) in the IVT-group compared to the non-IVT group (88.7% vs. 69.0%; OR=3.68, 95% CI=2.17-6.23). After adjusting for baseline characteristics and possible confounders IVT was the independent predictor of medication persistence (OR=2.93, 95% CI=1.48-5.81, p=0.002). Higher medication persistence was observed in patients with favorable long-term functional outcome, both in the IVT-group (OR=4.37, 95% CI=1.83-10.40, p<0.001) and the non-IVT-group (OR=3.46, 95% CI=1.84-6.52, p<0.001). CONCLUSION Medication persistence was higher among IVT-treated patients compared to non-IVT-treated patients. The higher rate of non- medication persistence was recorded among patients with more pronounced disabilities after stroke.

Intravenous thrombolysis and platelet count

Objective To study the effect of platelet count (PC) on bleeding risk and outcome in stroke patients treated with IV thrombolysis (IVT) and to explore whether withholding IVT in PC < 100 × 109/L is supported. Methods In this prospective multicenter, IVT register–based study, we compared PC with symptomatic intracranial hemorrhage (sICH; Second European-Australasian Acute Stroke Study [ECASS II] criteria), poor outcome (modified Rankin Scale score 3–6), and mortality at 3 months. PC was used as a continuous and categorical variable distinguishing thrombocytopenia (<150 × 109/L), thrombocytosis (>450 × 109/L), and normal PC (150–450 × 109/L [reference group]). Moreover, PC < 100 × 109/L was compared to PC ≥ 100 × 109/L. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from the logistic regression models were calculated. Results Among 7,533 IVT-treated stroke patients, 6,830 (90.7%) had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had thrombocytosis. Decreasing PC (every 10 × 109/L) was associated with increasing risk of sICH (ORadjusted 1.03, 95% CI 1.02–1.05) but decreasing risk of poor outcome (ORadjusted 0.99, 95% CI 0.98–0.99) and mortality (ORadjusted 0.98, 95% CI 0.98–0.99). The risk of sICH was higher in patients with thrombocytopenic than in patients with normal PC (ORadjusted 1.73, 95% CI 1.24–2.43). However, the risk of poor outcome (ORadjusted 0.89, 95% CI 0.39–1.97) and mortality (ORadjusted 1.09, 95% CI 0.83–1.44) did not differ significantly. Thrombocytosis was associated with mortality (ORadjusted 2.02, 95% CI 1.21–3.37). Forty-four (0.3%) patients had PC < 100 × 109/L. Their risks of sICH (ORunadjusted 1.56, 95% CI 0.48–5.07), poor outcome (ORadjusted 1.63, 95% CI 0.82–3.24), and mortality (ORadjusted 1.38, 95% CI 0.64–2.98) did not differ significantly from those of patients with PC ≥ 100 × 109/L. Conclusion Lower PC was associated with increased risk of sICH, while higher PC indicated increased mortality. Our data suggest that PC modifies outcome and complications in individual patients, while withholding IVT in all patients with PC < 100 × 109/L is challenged.