Time to Retire TPA in Acute Ischemic Stroke?

A new analysis supports the use of intravenous (IV) tenecteplase over IV alteplase (tissue plasminogen activator) for treatment of acute ischemic stroke.

The analysis found that patients with ischemic stroke treated with tenecteplase had a 5% higher likelihood of excellent recovery and a 10% higher likelihood of reduced disability 3 months after stroke than peers who were given alteplase.

There was no difference between tenecteplase and alteplase in the likelihood of a good recovery.

“Our meta-analysis shows that while both drugs have similar safety and increase the chances of good recovery after stroke, tenecteplase is superior to alteplase, with a greater chance of excellent recovery and reduced disability,” study author Georgios Tsivgoulis, MD, PhD, MSc, of the National and Kapodistrian University of Athens in Athens, Greece, said in a news release.

“These findings support transitioning to tenecteplase in clinical practice,” the study team concluded.

The study was published online on October 16 in Neurology.

The Preferred Choice

The meta-analysis included all 11 available studies that have evaluated the efficacy and safety of tenecteplase vs alteplase during IV thrombolysis for acute ischemic stroke within the first 4.5 hours after onset. In these studies, 3788 patients with stroke were treated with tenecteplase, and 3757 were treated with alteplase.

Compared with alteplase, tenecteplase was associated with a higher likelihood of achieving excellent (modified Rankin Scale [mRS] score, 0-1) functional outcomes (risk ratio [RR], 1.05; P = .012) and reduced disability (≥ 1-point reduction across all mRS scores) at 3 months (odds ratio [OR], 1.10; P = .034).

Good (mRS scores, 0-2) functional outcomes (RR, 1.03; P = .142) were similar between the groups.

There was no difference in safety outcomes, with similar rates of symptomatic intracerebral hemorrhage (RR, 1.12; P = .456) and 3-month mortality (RR, 0.97; P = .727).

The findings demonstrate that tenecteplase is “not only noninferior but also superior” to alteplase, Tsivgoulis and colleagues concluded. In their view, there are now sufficient data to transition to tenecteplase in clinical practice.

Reached for comment, Larry Goldstein, MD, chair, Department of Neurology, University of Kentucky, Lexington, Kentucky, said it points to a “significant but small difference” favoring tenecteplase over alteplase in patients with acute ischemic stroke treated within 4.5 hour of symptom onset.

“Many hospitals have already transitioned to tenecteplase because of the ease of administration,” said Goldstein, who wasn’t involved in the analysis.

In a linked editorial, Anna Ranta, MD, PhD, University of Otago, Wellington, New Zealand, said “we have had sufficient evidence to transition to tenecteplase in clinical practice for a while.” 

Ranta noted that studies have consistently confirmed the noninferiority of tenecteplase over alteplase, “with several asserting that tenecteplase is superior across either all patient groups or at least in certain subgroups, especially among patients with large vessel occlusion.”

Ranta also noted that tenecteplase has “significant practical advantages due to ease of administration, with studies showing reduced door-to-needle time and door-to-puncture time with tenecteplase over alteplase that benefit especially patients presenting to smaller hospitals and when transfers are required.”

“So, let us get on with it. Let us stop comparing the two, accept tenecteplase is at least as good as alteplase, probably overall slightly better, and acknowledge that it has significant workflow advantages that improve health equity,” Ranta added.

“Tenecteplase is the preferred choice. Instead of more comparative trials, let us focus our efforts on trials using tenecteplase to explore new frontiers for stroke thrombolysis,” she concluded.

The study had no targeted funding. Tsivgoulis, Ranta, and Goldstein had no relevant conflicts of interest.