Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study.

INTRODUCTION: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. PATIENTS AND METHODS: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. RESULTS: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4). DISCUSSION AND CONCLUSION: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Socioeconomic Inequalities in Functional Outcome After Reperfusion-Treated Ischemic Stroke.

BACKGROUND: We aimed to investigate whether socioeconomic status (SES) was associated with functional outcome in patients with ischemic stroke treated with reperfusion therapy (intravenous thrombolysis and/or thrombectomy). METHODS: This nationwide cohort study included reperfusion-treated patients with ischemic stroke ≥18 years registered in the Danish Stroke Registry between 2015 and 2018. Functional outcome was determined by the modified Rankin Scale score 90 days after stroke. SES was defined by educational attainment, family income, and employment status before stroke. SES data were available from Statistics Denmark and linked on the individual level with data from the Danish Stroke Registry. Uni- and multivariable ordinal logistic regression was performed for each socioeconomic parameter individually (education, income, and employment) to estimate the common odds ratios (cORs) for lower 90-day modified Rankin Scale scores. RESULTS: A total of 5666 patients were included. Mean age was 68.7 years (95% CI, 68.3-69.0), and 38.4% were female. Low SES was associated with lower odds for achieving lower 90-day modified Rankin Scale score: Low versus high education, cOR, 0.69 (95% CI, 0.61-0.79), low versus high income, cOR, 0.59 (95% CI, 0.53-0.67), and unemployed versus employed, cOR, 0.70 (95% CI, 0.58-0.83). Inequalities were reduced after adjusting for age, sex, and immigrant status, except for unemployed versus employed patients, adjusted cOR, 0.66 (95% CI, 0.54-0.80). No statistically significant differences remained after adjusting for potentially mediating variables (eg, stroke severity, prestroke modified Rankin Scale, and smoking). CONCLUSIONS: Socioeconomic inequalities were observed in functional outcome after reperfusion treated ischemic stroke. In particular, prestroke unemployment was negatively associated with good functional outcome. A more adverse prognostic profile among patients with low SES appeared to explain the majority of these inequalities.

Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke.

BACKGROUND: Reperfusion therapies (thrombolysis and thrombectomy) are of paramount importance for the recovery after ischemic stroke. We aimed to investigate if socioeconomic status (SES) was associated with the chance of receiving reperfusion therapy for ischemic stroke in a country with tax-funded health care. METHODS: This nationwide register-based cohort study included patients with ischemic stroke registered in the Danish Stroke Registry between 2015 and 2018. SES was determined by prestroke educational attainment, income level, and employment status. Data on SES was obtained from Statistics Denmark and linked on an individual level with data from the Danish Stroke Registry. Risk ratios (RR) for receiving reperfusion therapies were calculated using univariate and multivariable Poisson regression with robust variance. RESULTS: A total of 37 187 ischemic stroke patients were included. Low SES, as defined by education, income and employment status, was associated with lower treatment rates. The socioeconomic gradient was most pronounced according to employment status, with intravenous thrombolysis rates of 23.7% versus 15.8%, and thrombectomy rates of 5.1% versus 2.8% for employed versus unemployed patients. When the analyses were restricted to patients with timely hospital arrival, and adjusted for age, sex and immigrant status, low SES according to income and employment remained unfavorable for the likelihood of receiving intravenous thrombolysis: adjusted RR, 0.90 (95% CI, 0.86-0.95) for low versus high income, and adjusted RR, 0.77 (95% CI, 0.71-0.84) for unemployed versus employed patients. Similarly, low SES according to income and employment status remained unfavorable for the likelihood of receiving thrombectomy: adjusted RR, 0.83 (95% CI, 0.72-0.95) for low versus high income and adjusted RR, 0.68 (95% CI, 0.53-0.88) for unemployed versus employed patients. CONCLUSIONS: Socioeconomic inequalities in reperfusion treatment rates among ischemic stroke patients prevail, even in a country with tax-funded universal health care.

Thrombolysis in acute ischemic stroke is associated with lower long-term hospital bed day use: A nationwide propensity score-matched follow-up study.

Background Thrombolysis with intravenous recombinant tissue-type plasminogen activator improves functional outcome in acute ischemic stroke. Few studies have investigated the effects of thrombolysis in a real-world setting. We evaluated the impact of thrombolysis on long-term hospital bed day use and the risk of readmission due to stroke-related complications. Methods We conducted a register-based nationwide propensity score-matched follow-up study among ischemic stroke patients in Denmark (2004-2011). Thrombolysed patients were propensity-score matched with non-thrombolysed acute ischemic stroke patients admitted to stroke centers not yet offering thrombolysis in 2004-2006. The outcomes were length of the stroke admission, total all-cause hospital bed day use during the first year after the stroke, and the long-term risk of readmissions. Thrombolysed and non-thrombolysed patients were compared using multivariable log-linear regression and Cox regression. Results We identified 1095 thrombolysed and 1095 propensity score matched eligible but non-thrombolysed acute ischemic stroke patients. The median length of the stroke admission was 9 days in the thrombolysed group and 13 days in the non-thrombolysed group (adjusted geometric mean ratio, 0.88; 95% CI: 0.78-1.00). The median all-cause hospital bed day use within the first year was 12 days in the thrombolysed group and 19 days in the non-thrombolysed group (adjusted geometric mean ratio, 0.82; 95% CI: 0.73-0.92). There was no significant difference in the overall risk of readmission (adjusted hazard ratio, 0.91; 95% CI: 0.79-1.04); however, thrombolysis was associated with reduced risk of pneumonia (adjusted hazard ratio, 0.59; 95% CI: 0.35-0.97). Conclusions Thrombolysis in ischemic stroke was associated with lower long-term hospital bed day use and decreased risk of readmission due to pneumonia.

Acute ischemic stroke and long-term outcome after thrombolysis: nationwide propensity score-matched follow-up study.

BACKGROUND AND PURPOSE: Data on long-term outcome after intravenous tissue-type plasminogen activator (tPA) in ischemic stroke are limited. We examined the risk of long-term mortality, recurrent ischemic stroke, and major bleeding, including intracranial and gastrointestinal bleeding, in intravenous tPA-treated patients when compared with intravenous tPA eligible but nontreated patients with ischemic stroke. METHODS: We conducted a register-based nationwide propensity score-matched follow-up study among patients with ischemic stroke in Denmark (2004-2011). Cox regression analysis was used to compute adjusted hazard ratios for all outcomes. RESULTS: Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score-matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long-term mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.49-0.88). The long-term risk of recurrent ischemic stroke (adjusted hazard ratio, 1.05; 95% confidence interval, 0.68-1.64) and major bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.24-1.47) did not differ significantly between the intravenous tPA-treated and nontreated patients. CONCLUSIONS: Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival.

[Endovascular treatment of cerebral thrombosis in patient on dabigatran]. / Endovaskulær behandling af cerebral trombe ved samtidig behandling med dabigatran.

We report a case of severe acute ischaemic stroke in a patient who could not receive treatment with thrombolysis due to concomitant treatment with dabigatran (new anticoagulant drug). Endovascular treatment was the only treatment of choice. Due to well-organized prehospital logistics, including helicopter transport, the patient arrived at hospital shortly after onset of symptoms and was treated successfully with thrombectomy.