Background And Aims

Haemorrhagic transformation (HT) following thrombolysis is associated with poorer outcome. Measures of blood brain barrier permeability, such as extraction fraction, predict HT. We investigated whether HT incidence, accounting for extraction fraction, differed among acute ischaemic stroke (AIS) patients treated with alteplase or tenecteplase.

Methods

Technically adequate scans with perfusion defects and follow up imaging from 2 RCTs comparing alteplase with tenecteplase in AIS were analysed. Volumes of ischaemic core (relative cerebral blood flow <30%), ischaemic penumbra (delay time >3seconds and rCBF>30%), and extraction fraction >30% (E30) were calculated (MiStar). The proportion of E30 within the ischaemic lesion (E30%) was calculated. Logistic regression was used to identify factors predictive of HT defined as any intracranial haemorrhage by ECASS-2 criteria.

Results

Of 118 cases, 53 received alteplase and 65 tenecteplase. Baseline clinical and imaging characteristics were similar. HT occurred in 22/53 (41%) of alteplase and 19/65 (29%) of tenecteplase cases. Comparing HT and non-HT cases, a higher E30% was seen with tenecteplase (mean difference +15.9%, p=0.004) but not alteplase (+9.4% p=0.110). In a logistic regression model, baseline NIHSS and E30% were independently predictive of HT when correcting for age, systolic BP, antiplatelet history, and onset-to-treatment time. After adjustment for these variables there was a trend for reduced HT incidence with tenecteplase compared to alteplase (OR0.44(0.19-1.02), p=0.056).

Conclusions

After adjustment for clinical and imaging variables, there was a trend for lower incidence of HT with tenecteplase than alteplase. Future trials comparing alteplase and tenecteplase present an opportunity to evaluate relationships between drug allocation, HT and E30%.

Trial Registration Number

ATTEST - 2010-024541-67 ( EudraCT Number )

A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke - Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347