Abstract TP048: Body Weight-Adapted Fibrinolysis Dosing Schemes in Acute Ischemic Stroke and ST-Elevation Myocardial Infarction: A Risk–Benefit Analysis

Introduction: Body weight (BW)-adapted dosing schemes for tenecteplase (TNK) and alteplase (ALT) vary. Determining whether dosing schemes affect efficacy and safety outcomes is key to facilitating treatment in emergencies where precise weight measurement is often not possible. We conducted a post hoc analysis of two BW dosing schemes (mg/kg dosing vs 10 kg BW categories) using TNK and ALT data from acute ischemic stroke (AIS) and ST-elevation myocardial infarction (STEMI) trials. Methods: Patient-level data from the STTC meta-analysis, in which ALT was dosed in mg/kg, were stratified into 10 kg BW categories used in the AcT trial (<60 to ≥90 kg), with further subcategories (<50, 50–59, 90–99, and ≥100 kg). Outcomes were compared between stratified STTC data (control vs ALT) and AcT trial data (ALT vs TNK) by BW category across datasets, and across BW categories within each dataset. This was repeated using data from key AIS (ORIGINAL, EXTEND-IA TNK, and ATTEST-2) and STEMI (ASSENT-2 and -3 and STREAM-1 and -2) trials. AIS and STEMI outcomes were not directly compared. Outcomes for AIS were modified Rankin Scale (mRS) 0–1 at Days 90–120, deaths up to Day 90, and symptomatic intracerebral hemorrhage (sICH); for STEMI, these were deaths up to Day 30, in-hospital major bleeds, and sICH up to Day 30. Forest plots were used to compare treatments by BW category; odds ratios were unadjusted unless otherwise specified. Results: Across all datasets, patients with lower BW tended to be female and elderly; those with higher BW tended to be male and younger. Outcomes were similar between STTC (N=4,361) and AcT (N=1,563) across BW groups ( Fig. 1 ), including those in which the AcT dosing scheme led to greater dose variation. For example, the <50 kg group had more deaths up to Day 90 but a similar proportion of sICH vs the other groups; findings in this group were similar between TNK and ALT. No other relationship between mRS 0–1, death, or sICH and BW was established ( Table 1 ). Findings were similar in other AIS and STEMI trials ( Fig. 2 ). Conclusions: Outcomes were comparable between the two BW dosing schemes for TNK and ALT across BW categories and were supported by other trials in AIS and STEMI. Limitations include the uncertain accuracy of BW measurements, low proportion of sICH across trials, lack of adjustment for baseline variables across trial datasets, and exploratory nature of the analysis. The safety of each dosing scheme was similar in patients with low BW.