Sex differences in stroke reperfusion therapy in Aotearoa (New Zealand).

BACKGROUND AND AIMS: Stroke is a leading cause of death in Aotearoa (New Zealand), and stroke reperfusion therapy is a key intervention. Sex differences in stroke care have previously been asserted internationally. This study assessed potential differences in stroke reperfusion rates and quality metrics by sex in Aotearoa (New Zealand). METHODS: This study used data from three overlapping sources. The National Stroke Reperfusion Register provided 4-year reperfusion data from 2018 to 2021 on all patients treated with reperfusion therapy (intravenous thrombolysis and thrombectomy), including time delays, treatment rates, mortality and complications. Linkage to Ministry of Health administrative and REGIONS Care study data provided an opportunity to control for confounders and explore potential mechanisms. T-test and Wilcoxon rank-sum analyses were used for continuous variables, while the chi-squared test and logistic regression were used for comparing dichotomous variables. RESULTS: Fewer women presented with ischaemic stroke (12 186 vs 13 120) and were 4.2 years older than men (median (interquartile range (IQR)) 79 (68-86) vs 73 (63-82) years). Women were overall less likely to receive reperfusion therapy (13.9% (1704) vs 15.8% (2084), P < 0.001) with an adjusted odds ratio of 0.83 (0.77-0.90), P < 0.001. The adjusted odds ratio for thrombolysis was lower for women (0.82 (0.76-0.89), P < 0.001), but lower rates of thrombectomy fell just short of statistical significance ((0.89 (0.79-1.00), P = 0.05). There were no significant differences in complications, delays or documented reasons for non-thrombolysis. CONCLUSIONS: Women were less likely to receive thrombolysis, even after adjusting for age and stroke severity. We found no definitive explanation for this disparity.

Tenecteplase real-world data: A three phase sequential comparison.

INTRODUCTION: The New Zealand (NZ) Central Region Stroke Network, serving 1.17 million catchment population, changed to tenecteplase for stroke thrombolysis in 2020 but was forced to revert to Alteplase in 2021 due to a sudden cessation of drug supply. We used this unique opportunity to assess for potential before and after temporal trend confounding. PATIENTS AND METHODS: In NZ all reperfused patients are entered prospectively into a national database for safety monitoring. We assessed Central Region patient outcomes and treatment metrics over three time periods: alteplase use (January 2018-January 2020); during switch to tenecteplase (February 2020-February 2021) and after reverting to alteplase (February 2021-December 2022) adjusting regression analyses for hospital, age, onset-to-needle, NIHSS, pre-morbid mRS and thrombectomy. RESULTS: Between January 2018 and December 2022, we treated 1121 patients with Alteplase and 286 with tenecteplase. Overall, patients treated with tenecteplase had greater odds of favorable outcome ordinal mRS [aOR = 1.43 (95% CI = 1.11-1.85)]; shorter door-to-needle (DTN) time [median 52 (IQR 47-83) vs 61 (45-84) minutes, p < 0.0001] and needle to groin (NTG) times [118 (74.5-218.5) vs 185 (118-255); p = 0.02)]. Symptomatic intracerebral hemorrhage (sICH) rate was lower in tenecteplase group [aOR 0.29 (0.09-0.95)]. Findings similarly favored tenecteplase when comparing tenecteplase to only the second alteplase phase. There was no inter-group difference when comparing the two alteplase phases. CONCLUSIONS: Our results suggest that previously reported benefits from tenecteplase in a real-world setting were not likely attributable to a temporal confounding.

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Prehospital Telestroke vs Paramedic Scores to Accurately Identify Stroke Reperfusion Candidates: A Cluster Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Stroke reperfusion therapy is time critical. Improving prehospital diagnostic accuracy including the likelihood of large vessel occlusion can aid with efficient and appropriate diversion decisions to optimize onset-to-treatment time. In this study, we investigated whether prehospital telestroke improves diagnostic accuracy when compared with paramedic assessments and assessed feasibility. METHODS: We conducted a pragmatic, community-based, cluster randomized controlled trial comparing the diagnostic accuracy of telestroke assessments inside the ambulance with a modified Los Angeles Motor Scale (PASTA score). The primary outcome was the accuracy of predicting reperfusion candidates; secondary outcomes were accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of either approach to identify IV thrombolysis (IVT) and endovascular thrombectomy (EVT) candidates and true stroke patients by study group. The accuracy of telestroke and PASTA assessments was compared against in-person assessment in the emergency department and with the final diagnosis/intervention for the patient. We also monitored for technical challenges. RESULTS: We recruited 76 patients (35 telestroke and 41 PASTA) between August 2019 and September 2020. The mean age was 72.2 (±14.6) years. Telestroke was 100% (95% CI 90%-100%) and PASTA 70.7% (54.5%-83.9%) accurate in predicting reperfusion candidates compared with preimaging emergency department neurologist assessment (p < 0.001). When compared with actual reperfusion therapy administered, the predictive accuracy was 80% (63.1%-91.6%) and 60.1% (44.5%-75.8%) for telestroke and PASTA, respectively (p < 0.001). In predicting the administration of IVT, telestroke was 80% (63.1-91.6) and PASTA was 56.1% (39.8-71.5) accurate (p < 0.001). In predicting intervention with EVT, telestroke was 88.6% (73.3-96.8) and PASTA 56.1% (39.8-71.5) accurate (p = 0.005). The service model proved technically feasible and was acceptable to neurologists. DISCUSSION: Prehospital telestroke assessment is feasible, accurate, and superior to the PASTA score in predicting acute reperfusion therapies, presenting an effective option to guide prehospital diversion decisions. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001678189).anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378655&isReview=true. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intra-ambulance telestroke evaluation has a greater diagnostic accuracy compared with the PASTA score performed by paramedics in distinguishing hyperacute stroke patients who are candidates for reperfusion therapy.

Stroke reperfusion treatment trends in New Zealand: 2019 & 2020.

AIM: This study assessed stroke reperfusion treatments trends in 2019 and 2020 with comparison back to 2015. Additional analyses looked at differences by sex and ethnicity. METHOD: The National Stroke Register contains data on all stroke patients who received reperfusion therapies since 2015. Outcomes included treatment rates, delays, mortality and complications by year, sex, and ethnicity. Continuous variables were compared using the Wilcoxon Rank-Sum Test and presented as p-values. Rate-based results were compared using incidence rate comparison and presented as p-values +/- 95% confidence intervals. RESULTS: In 2020, 11.3% (828/7333) received intravenous thrombolysis (IVT) and 5.5% (404/7333) underwent stroke clot retrieval (SCR), increasing from 6.5% (389/5963) and 0.5% (30/5963) in 2015, respectively. Among reperfused patients (IVT, SCR, both), 8.3% had died at seven days and 3.0% (29/959) experienced sICH. Door-to-treatment time was stable between 2019 and 2020, with median (IQR) of 61 (44-84) and 61 (41-87) minutes, respectively. Initial presentation to a SCR centre was associated with shorter onset-to-reperfusion time of 286 (206-566) minutes, compared with 403 (295-550) minutes (p<0.001). While onset-to-door time was shorter for Maori (72 (44-112) minutes, p<0.001) and Pacific patients (70 (48-105) minutes, p=0.03) compared with NZ Europeans, door-to-needle time was longer in Maori (66 (48-88) compared to 59 (41-83) minutes (p=0.001). Female (73.7+/15.3 years) patients were on average 4.4 years older than males (69.3+/-14.6 years) and less likely to receive thrombolysis (12.7% vs 14.9%, p=0.02). CONCLUSION: Reperfusion therapy rates continue to rise, now driven by increasing rates of SCR. Longer door-to-needle time in Maori and lower reperfusion rates in women require further exploration and attention.

Switching to Tenecteplase for Stroke Thrombolysis: Real-World Experience and Outcomes in a Regional Stroke Network.

Background and Purpose: Due to practical advantages, increasing trial safety data, recent Australian Guideline endorsement and local population needs we switched to tenecteplase for stroke thrombolysis from alteplase. We describe our change process and real-world outcome data. Methods: Mixed-methods including stakeholder engagement, preimplementation and postimplementation surveys, and assessment of patient treatment rates, metrics, and clinical outcomes preimplementation and postimplementation adjusting regression analyses for age, sex, National Institutes of Health Stroke Scale, premorbid modified Rankin Scale score, and thrombectomy using New Zealand National Stroke Registry data. Results: Preswitch consultation involved stroke and emergency clinicians, pharmacists, national regulatory bodies, and hospital legal teams. All survey responders (90% response rate) supported the proposed change and remained satisfied 12 months postimplementation. Between January 2018 and February 2021, we treated 555 patients with alteplase and 283 with tenecteplase. Patients treated with tenecteplase had greater odds of a favorable modified Rankin Scale using both shift (adjusted odds ratio, 1.60 [95% CI, 1.15­2.22]) and dichotomous analyses (modified Rankin Scale score, 0­2; adjusted odds ratio, 2.17 [95% CI, 1.31­3.59]) and shorter median (interquartile range) door-to-needle time (median, 53 [38­73.5] versus 61 minutes [45­85], P=0.0002). Symptomatic intracranial hemorrhage rates (tenecteplase 1.8% versus 3.4%; adjusted odds ratio, 0.46 [95% CI, 0.13­1.64]), death by day 7 (tenecteplase 7.5% versus 11.8%; adjusted odds ratio, 0.46 [95% CI, 0.21­0.99]), and median (interquartile range) needle to groin time for the 42 transferred regional patients (tenecteplase 155 [113­248] versus 200 [158­266]; P=0.27) did not significantly differ. Conclusions: Following stakeholder endorsement, a region-wide switch from alteplase to tenecteplase was successfully implemented. We found evidence of benefit and no evidence of harm.