Tenecteplase reduces the need for thrombectomy compared to alteplase


Results from the Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) study show that the use of tenecteplase (0.25mg/kg) led to increased reperfusion at the initial angiogram. If 9.1 patients were treated with tenecteplase instead of alteplase, the need for thrombectomy was avoided in one patient. There were also improved functional outcomes and no safety concerns. The results were announced at the International Stroke Conference (ISC; 24–26 January, Los Angeles, USA)

“Guidelines recommend that thrombolysis be given to eligible patients before thrombec­tomy,” said Bruce Campbell (Royal Melbourne Hospital, University of Melbourne, Parkvillle, Australia), co-principal investigator and medical coordina­tor. “As there is often quite a gap while patients are being transferred within a hospital or between hospitals to get their endovascular thrombectomy, improving intravenous thrombolysis can potentially get earlier reperfusion and better outcomes for patients.”

Tenecteplase is a genetically modified tissue plasminogen activator (tPA) that has greater fibrin specificity and longer half-life permitting convenient single-bolus administration and it has replaced alteplase as a standard lytic in myocardial infarction. There are some previous studies that have suggested improved reperfusion and clinical outcome with tenecteplase versus alteplase in stroke patients.

“Our hypothesis in EXTEND-IA TNK was that patients who are having endovascular thrombectomy would have a better reperfusion at the initial angiogram with tenecteplase rather than alteplase,” continued Campbell. “It was an investigator initiated prospective randomised open-label blinded end-point study. We did a meta-analysis of EXTEND-IA, SWIFT PRIME and ESCAPE and found that overall 7.5% of patients recanalised or reperfused with alteplase prior to thrombectomy. The confidence interval goes down to 4.6%, half of that is 2.3% so the non-inferiority boundary was set at -2.3%. We would then test superiority if non-inferiority was demonstrated and we had an interim sample size recalculation after 100 patients, which set a final sample of 202.”

The study enrolled large vessel occlusion patients eligible for thrombolysis at 13 centres across Australia and New Zealand. Three of them were “spoke” sites that transferred their patients to a comprehensive centre, the patients were then randomised 1:1 to tenecteplase 0.25mg/kg and alteplase 0.90mg/kg. The primary outcome was the mTICI score on the initial angiogram. They also looked at 24 hour reperfusion, day three National Institue of Health Stroke Score (NIHSS) and 90-day centralised mRS.

The inclusion criteria were very broad; there was no upper age limit and no NIHSS restrictions. Internal carotid artery (ICA), M1, M2 and basilar occlusions were all included in the trial. The thrombectomy had to begin within six hours of stroke and patients needed to be eligible for thrombolysis using local criteria.

There were 101 patients in each group (tenecteplase and alteplase), after two were withdrawn due to withdrawal of consent or investigator randomisation error, and they were all followed up though to day 90.

The demographics of the group where typical of thrombectomy patients; an average age of around 70 and a median NIHSS score of 17 in both groups. The time from onset to lysis was about two hours and there was an average of 55 minutes between when the lysis was given and when the initial angiogram was performed. About a quarter of the patients had carotid occlusions, a handful of basilar and most of them were M1 occlusions with a few M2s.

The primary outcome showed alteplase opened the artery in 10% of cases, just the same as EXTEND-IA, and it was increased to 22% with tenecteplase, which was not just non-inferior but statistically significantly superior, with a risk difference of 12% and an odds ratio of 2.6.

“For the secondary outcome our primary interest was the ordinal analysis of the Rankin and the distribution there is actually statistically significant,” said Campbell. “There was an odds ratio of 1.7, p value of 0.037, adjusted for age and NIHSS, in favour of tenecteplase.”

The limitations are that these results apply to the thrombectomy population, which is only around 13% of all ischaemic stroke patients but these patients do contribute disproportionately to the disability burden after stoke.

Overall, in comparison to 0.9mg/kg alteplase, 0.25mg/ kg tenecteplase led to increased reperfusion at the initial angiogram. There were also improved functional outcomes and no safety concerns.

“Tenecteplase has the convenience of a single bolus, which is helpful in patients when they are being moved between hospitals and there is also the potential for a reduction in cost,” said Campbell, “If you look at 50mg of tenecteplase which is enough to treat a patient of any weight versus 100mg alteplase, the wholesale price comparison is US$5861.67 per 50mg tenecteplase vs US$8800.36 per 100mg alteplase.”


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