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.

Systemic risk factors associated with progression of atherosclerosis from the coronary to the carotid arteries.

BACKGROUND: It is unclear why atherosclerosis remains restricted to one arterial tree in some patients whereas it is more generalized in others. Few studies have addressed the role that systemic risk factors play in the progression of atherosclerosis from one arterial tree to another. METHODS: We studied 344 consecutive patients with suggested coronary artery disease (CAD) who underwent combined coronary and carotid angiography during a 7-month period. Coronary and carotid disease was graded as absent-mild or moderate-severe based on the degree of stenosis of these vessels. Traditional vascular risk factors were compared for patients with moderate-severe CAD alone versus patients with moderate-severe CAD and carotid disease. RESULTS: Moderate-severe CAD alone was found in 162 patients and moderate-severe CAD and carotid disease was found in 100 patients. Multivariate analysis showed that hypertension (P = .007, odds ratio 2.2, 95% confidence interval 1.2-3.9), history of smoking (P = .06, odds ratio 1.8, 95% confidence interval 1.0-3.4), and diabetes (P = .09, odds ratio 1.6, 95% confidence interval 0.9-2.8) were associated with combined moderate-severe CAD and carotid disease. Patients with combined moderate-severe CAD and carotid disease were significantly more likely to have at least 2 of these 3 risk factors (P < .001) than patients with moderate-severe CAD alone. CONCLUSION: An accumulating burden of hypertension, diabetes, and smoking are important in the progression of atherosclerosis from the coronary to the carotid circulation.