Abstract Body: Introduction: Many centers have opted to make the transition from alteplase to tenecteplase over the past three years. Making major treatment changes in a healthcare setting has its challenges. This transition period gave us a unique opportunity to assess patient outcomes comparing both drugs with the same healthcare system with similar patient populations.

Hypothesis: Patients who received tenecteplase will have shorter door-to-needle (DTN) times and better outcomes as measured by 90-day Modified Rankin Scores (mRS) with no significant increase in symptomatic ICH (sICH) when compared to patients who received alteplase.

Methods: Differences between continuous variables were analyzed using the student’s t-test and Wilcoxon rank test, and the chi-squared test for categorical variables. The primary independent variable was the binary group (tenecteplase vs. alteplase). A generalized linear model was built for the outcome DTN and logistic regression model for the binary outcome (mRS ≤2 as good, >2 as poor) controlling for demographics, comorbidities, NIHSS, LKW time and ICH admission. Odds ratios (OR) and 95% confidence intervals (CI) were reported, with all analyses performed in R v4.4.1.

Results: The dataset was extracted from the HDSA (with a HOPES registry subgroup), including 574 patients—323 in the alteplase group and 251 in the tenecteplase group. The mean age was similar between groups (66.06 vs. 65.9 years; P=0.88), as was the mean DTN (46.9 vs. 48.9 minutes; P=0.11). A multivariable generalized linear model, adjusted for demographics and comorbidities, showed no significant difference in DTN between the groups (Δβ = -3.04 [95% CI -8.33 to 2.25]; P=0.26). However, in a subgroup analysis looking at the HOPES registry from a single center, a multivariable logistic regression, also adjusted for demographics and comorbidities, indicated that patients in tenecteplase had lower odds of poor functional outcomes at 90 days compared to alteplase (OR = 0.11 [95% CI 0.01–0.84]; P=0.03).

Conclusion: While DTN times did not improve with the transition to tenecteplase, we do see that patients who received tenecteplase were less likely to have poor outcomes as defined by an mRS of 3-6 based on our subgroup analysis. The rate of sICH was also comparable between the two groups. Additional post-implementation studies should be considered to assess trends in mRS outcomes as more stroke centers transition to use of tenecteplase in acute ischemic stroke.