The Impact of CT Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke. Analysis of Two Randomized Controlled Trials
Background—We pooled two clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, one demonstrating superiority of tenecteplase, while the other showed no difference between the treatments on patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcome in the group of patients with target mismatch as identified with advanced imaging.
Methods—We investigated if tenecteplase treated patients had a different 24h reduction in the National Institutes of Health Stroke Scale (NIHSS) and a favourable odds ratio of a modified Rankin scale (mRS) of 0-1vs 2-6 compared with alteplase treated patients using linear regression to generate odds ratios (OR). Imaging outcomes included rates of vessel recanalisation and infarct growth at 24 hours and occurrence of large parenchymal haematoma. Baseline CT perfusion was analysed to assess if patients met the target mismatch criteria (absolute mismatch volume >15mL, mismatch ratio >1.8, an baseline ischemic core <70mL, and volume of severely hypoperfused tissue <100mL). Patients meeting target mismatch criteria were analysed as a subgroup to identify if they had different treatment responses than the pooled group.
Results—From 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase treated patients had greater early clinical improvement (median NIHSS change, tenecteplase 7, alteplase 2, p=0.018) and less parenchymal haematoma (2/75 vs 10/71, p=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (mRS 0-1 OR 1.77, 95% CI 0.89-3.51, p=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median NIHSS change, tenecteplase 6, alteplase 1, p<0.001) and better late independent recovery (mRS 0-1, OR 2.33, 95% CI 1.13-5.94, p=0.032) than those treated with alteplase.
Conclusions—Tenecteplase may offer an improved efficacy and safety profile versus alteplase, benefits possibly exaggerated in patients with baseline CT perfusion defined target mismatch.
Clinical Trial Registration—NCT01472926, https://clinicaltrials.gov and ACTRN12608000466347, https://www.anzctr.org.au
- Received April 7, 2016.
- Revision received September 6, 2016.
- Accepted December 1, 2016.