tPA before mechanical thrombectomy: To SKIP or not?

Skipping intravenous (IV) tissue plasminogen activator (tPA) before mechanical thrombectomy (MT) may have similarly favourable outcomes to using tPA pre-MT in patients with acute stroke, according to the SKIP* study presented at ISC 2020.

“Both IV tPA and MT have [proven] evidence for benefits in ischaemic stroke patients, … [but] we really don’t know whether [skipping] IV [tPA] before MT is indeed for LVO** patients,” said Dr Kentaro Suzuki from the Department of Neurology at Nippon Medical School Hospital in Tokyo, Japan.

The researchers conducted a prospective, open-label trial involving 204 acute ischaemic stroke patients with LVO at 23 sites in Japan. Patients were randomly assigned to the direct MT group (MT only; n=101, median age 74 years, 55 percent male) or bridging group (MT with tPA; n=103, median age 76 years, 70 percent male). The primary endpoint of the study was a modified Rankin Scale (mRS) score of 0–2 at 90 days. [ISC 2020, LB18]

Results showed that mRS score of 0–2 at 90 days was achieved by a similar percentage of patients who had direct MT therapy or bridging therapy (59.4 percent vs 57.3 percent; odds ratio, 1.09, 95 percent confidence interval [CI], 0.63–1.90; p=0.17 for noninferiority, which exceeded the noninferiority margin of 0.74).

With regard to safety, a significantly lower rate of intracranial haemorrhage (ICH) was observed in the direct MT group compared with the bridging group within 36 hours after onset (34.0 percent vs 50.0 percent; hazard ratio, 0.50, 95 percent CI, 0.28–0.88; p=0.02).

“We could not prove noninferiority of direct MT to bridging therapy [in this study] … as the frequency of favourable outcome due to high recanalization rate was higher than [what] we expected,” said Suzuki. “[However, the] frequency of favourable outcomes did not differ between [groups] … any ICH was significantly less frequent in [the] direct MT group.”

“We feel that giving alteplase [the most commonly administered tPA] to dissolve clots is not necessary, and mechanical clot removal can be performed immediately,” Suzuki said. “If we skip alteplase, we can perform MT with low risk of bleeding.”

“The best strategy is usually to treat with [alteplase] … and then if the patient is eligible, the patient goes for endovascular therapy as well,” said Professor Mitchell Elkind from Columbia University Medical Center of the NewYork-Presbyterian Hospital in New York, US, and president-elect of the American Heart Association (AHA), in a press release. “But [we] don’t skip that initial step because sometimes the endovascular therapy [or direct MT therapy] gets delayed or doesn’t occur for some reason or another.”

“[T]he AHA/American Stroke Association [currently] recommends using IV therapy within the 4.5 hour-time window and then treating with mechanical clot removal, if appropriate,” Elkind added.

*SKIP: Randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion - A prospective, multicenter, randomized trial

**LVO: Large vessel occlusion