Abstract TMP23: Third International Stroke Trial (IST-3): Subgroup Effects of iv rt-PA < 6 hrs in Acute Ischaemic Stroke on Symptomatic Intracranial Haemorrhage and Outcome at 6 Months
Aim: In IST-3 patients, our aim was to assess whether effects of iv thrombolysis with recombinant tissue plasminogen activator (rt-PA) on symptomatic intracranial haemorrhage (SICH) within 7 days & Oxford Handicap Score (OHS) at 6 months were modified by baseline characteristics.
Methods: Randomised trial of iv rt-PA (0.9mg/kg) (n=1515) versus control (n=1520). SICH within 7 days was identified by blinded central review by an expert panel. Functional status was assessed by the OHS at six months by postal questionnaire or blinded telephone interview. OHS was analysed by logistic ordinal regression, and all analyses were adjusted for key baseline prognostic factors (age, NIHSS, hours delay from onset to randomisation, and presence of visible ischaemia on the baseline scan). The trial is registered: ISRCTN25765518.
Results: Fatal or non-fatal SICH within 7 days occurred in 104 (7%) vs 16 (1%), adjusted OR 6·96 (95% CI 3·45-14·0). Among patients allocated rt-PA, the absolute risk of SICH was higher with increasing age, NIHSS, predicted probability of poor outcome, ischaemic change on baseline imaging, systolic or diastolic blood pressure, blood glucose and treatment with antiplatelet agents in the 48 hours before randomisation, but not with time delay to randomisation or presence of AF. However, there were no significant interactions of the adjusted effect of rt-PA on SICH with any of the measured baseline variables except the use of antiplatelet agents. Ordinal analysis of OHS at 6 months favoured rt-PA (adjusted common odds ratio 1·27,95% CI 1·10- 1·47 p=0·001). There were no significant treatment interactions except for a positive interaction with NIHSS (p=0.018).
Conclusion: Of baseline factors associated with a higher risk of SICH among controls, only prior antiplatelet therapy significantly modified the treatment-related risk of SICH. None of the measured variables significantly modified the favourable shift in OHS score at six months with treatment, except for an unanticipated positive interaction, suggesting that benefit was greater in more severe strokes.
- © 2012 by American Heart Association, Inc.