Switching to Tenecteplase for Stroke Thrombolysis May Boost Outcomes

Making the switch from alteplase to tenecteplase for stroke thrombolysis can be done successfully when the appropriate preparations are taken, and it may improve patient outcomes, the experience of a regional stroke network in New Zealand shows.

Patients treated with tenecteplase had shorter door-to-needle times and better functional outcomes compared with those treated when alteplase was the go-to agent, with no significant differences in symptomatic intracranial hemorrhage rates, early death, or needle-to-groin times (for those transferred to a thrombectomy center).

There was one dosing error, in which the higher tenecteplase dose meant for MI was administered, but “the patient recovered well,” Karim Mahawish, MBChB (Palmerston North Hospital, New Zealand), and colleagues report in a study published online in Stroke. Mahawish presented the results during the virtual 7th European Stroke Organisation Conference last week.

Tenecteplase has several advantages over alteplase, senior author Anna Ranta, MD, PhD (University of Otago, Wellington, New Zealand), told TCTMD, including greater fibrin specificity, faster onset of action, and a longer half-life. Importantly, it’s easier to administer—in a single IV bolus as opposed to the 1-hour infusion needed with alteplase. That simplifies the process of transferring patients from an outlying hospital to a thrombectomy center, a key factor driving the switch in thrombolytics within their stroke network, in which more than half of patients require transport and transfers can take up to 5 hours, Ranta said.

The move also was motivated by evidence from the EXTEND-IA TNK trial showing that tenecteplase improves reperfusion and clinical outcomes versus alteplase in patients with large-vessel occlusions (LVOs) eligible for stroke thrombectomy and by a strong recommendation in the Australian stroke guidelines, Ranta added.

When stroke networks aren’t seeing much in the way of delays when transferring patients from a referral hospital to a thrombectomy center and may not derive much benefit from switching to tenecteplase, “then I think it’s very reasonable, it’s probably appropriate, to wait for the current randomized controlled trials to be finished to have that extra data to really be convinced that [tenecteplase is] better,” Ranta said, referring to ongoing trials that include TASTE and ETERNAL-LVO.

She added, “I actually do believe it is better,” a conclusion that will likely become more certain once the trials are complete. “I think we will see a change. I think this will happen across the world. And it’s going to be worth the effort, because I think [tenecteplase] will be better,” she said. However, stroke networks that are transferring a large proportion of their patients to a thrombectomy center should start thinking about moving to tenecteplase now, she stressed.

“Those patients I believe are clearly disadvantaged at the moment if we continue with alteplase in that group,” Ranta said. “If you have a large regional network and there are transport delays and difficulties, I think you really need to consider making the change.”

Study Provides Reassurance

In the study, Mahawish, Ranta, and colleagues describe their experience in making the switch from alteplase to tenecteplase within the New Zealand Central Region Hyper-Acute Stroke Network, which consists of seven spoke hospitals and one hub center capable of performing thrombectomy.

All institutions within the network made the change on March 2, 2020, but only after extensive preparations that included discussions with stroke and emergency clinicians, pharmacists, regulators, and legal teams. A survey sent out before the move showed that stroke specialists unanimously supported it, and a follow-up survey sent a year after implementation “affirmed confidence using tenecteplase, that administration complexity was reduced, and that care processes were expedited,” the investigators report.

I think this will happen across the world. And it’s going to be worth the effort. Anna Ranta

To assess the impact of moving to tenecteplase, the researchers examined data on 555 patients treated with alteplase before the change and 283 with tenecteplase after implementation. The two groups were similar, although tenecteplase-treated patients had a higher median onset-to-door time (89 vs 80 minutes; P = 0.01) and were more likely to undergo thrombectomy (16% vs 6%; P < 0.001).

Median door-to-needle time was shorter with tenecteplase (53 vs 61 minutes; P = 0.0002), which “appears related to higher rate of in-CT thrombolysis facilitated by a single-bolus injection,” Mahawish et al write.

Moreover, patients treated with tenecteplase had higher odds of a favorable functional outcome assessed by modified Rankin Scale (mRS) scores, both in a shift analysis (adjusted OR 1.60; 95% CI 1.15-2.22) and in an analysis looking at achievement of an mRS score of 0 to 2 (adjusted OR 2.17; 95% CI 1.31-3.59).

Ranta noted that some caution is advised in interpreting this finding, acknowledging the limitations of an observational analysis but also pointing to the extensive statistical measures employed. “I don’t think that this study provides the evidence that tenecteplase is better,” she said. “I think this study provides reassurance that if you do make the change, it’s safe and is potentially associated with better patient outcomes.”

Lessons Learned

Because there are still trials comparing tenecteplase and alteplase for stroke thrombolysis being completed, it was important to make sure all key stakeholders were comfortable making the switch to tenecteplase before doing so, Ranta said. Surveys indicated that, though there was support for the change, there were concerns about legal issues related to the fact that tenecteplase is not currently approved for use in stroke. Those were addressed by consulting hospital legal teams. It was also crucial to engage early on with emergency department and nursing staff, as well as pharmacists, so they could be part of the process, Ranta said.

A critical component was switching completely to tenecteplase from alteplase across all centers within the stroke network and for all patients eligible for thrombolysis, to minimize the risk of dosing errors. Ranta explained that previously there had been issues with patients with stroke receiving tenecteplase instead of alteplase, but at the much-higher alteplase dose, resulting in fatal cerebral hemorrhages.

Although tenecteplase is also used in the setting of acute MI, the cardiac dose is only twice as high as the stroke dose, so if an accidental mix-up occurs, the consequences are likely to be less dire than if tenecteplase is confused with alteplase.

“The risk of giving a wrong dose of tenecteplase in a setting where every patient gets tenecteplase is actually, I believe, less than having two drugs used concurrently,” Ranta said, noting that as an extra safety measure, the tenecteplase kits for stroke come in different boxes than those for MI.

Taking the time to educate staff is extremely important, Ranta stressed, pointing out that the whole process took several months.

Commenting for TCTMD, Larry Goldstein, MD (University of Kentucky, Lexington), pointed to the ease of administration as a positive for tenecteplase versus alteplase, but he noted that the lack of US Food and Drug Administration approval for tenecteplase in stroke thrombolysis—and the availability of an approved alternative—is standing in the way of wider adoption.

Nevertheless, he said, “my own feeling is that eventually it will be approved [for stroke] and that it will probably be used, at least as an alternative.”

Goldstein pointed out that tenecteplase can already be found in acute ischemic stroke guidelines from the American Heart Association/American Stroke Association, with class IIb recommendations suggesting use of tenecteplase as an alternative to alteplase in patients eligible for thrombectomy and in those with minor neurological impairment and no major intracranial occlusion.

“There are currently no [American Heart Association] guideline recommendations for the use of tenecteplase for stroke thrombolysis outside of these settings,” Goldstein said. “If guidelines are revised based on additional data and the approach gains FDA approval, more widespread adoption would likely follow.”