Abstract 209: The Most Accurate Definition of Clinically Relevant Hemorrhagic Transformation after Thrombolytic Therapy for Stroke: Analysis of the NINDS-TPA Trials
Background: Multiple contending definitions have been advanced to distinguish clinically relevant from incidental hemorrhagic transformation (HT) after intravenous tissue plasminogen activator (IV TPA) for acute ischemic stroke. We examined which definition best identified hemorrhages that altered patient final outcome in the two NINDS-TPA trials.
Methods: Ten definitions of clinically relevant hemorrhage were analyzed, based on radiologic (HI, PH, both) and clinical (asymptomatic, any early worsening, early NIHSS worsening by 4 or more) findings. Candidate definitions included any radiologic hemorrhage, any parenchymal hematoma, and definitions of SICH from the NINDS-TPA Study (any HT judged causally related to any worsening), ECASS 3 (any HT and ≥ 4 NIHSS worsening), and modified SITS-MOST (PH and ≥ 4 NIHSS worsening). Using a 15-variable prognostic model derived from the placebo group, we compared the actual 3 month global disability outcomes for patients following TPA and HT with their predicted outcomes had they not received TPA.
Results: Among the 312 patients treated with IV tPA, 48 (15.4%) experienced any radiologic ICH. Among the ten candidate definitions, the ECASS 3 definition best distinguished hemorrhages that altered final outcome (figure). ECASS 3 positive hemorrhage patients had worse actual (with TPA) vs predicted (without TPA) outcomes, with mean final mRS 5.6 vs 3.6 and death in 75% vs 26.8%. ECASS 3 hemorrhage patients without ≥ 4 NIHSS worsening had no difference between actual and predicted outcomes, with mean final mRS 4.2 vs 4.1 and death in 35% vs 37%. In the two NINDS-TPA trials, rates of ECASS 3 hemorrhages in the TPA vs placebo group were 5.1% (95CI 3.2–8.2%) vs 1.3% (95CI 0.5–3.2%).
Conclusions: The clinically important hemorrhage definition that best identifies hemorrhages that alter final global disability and fatal outcome is any radiologic HT associated with ≥ 4 early NIHSS worsening. Asymptomatic hemorrhages have no adverse impact on final outcomes.
- © 2012 by American Heart Association, Inc.