Treatment of patients following ischemic stroke was the focus of three separate studies published in JAMA, two of which involved use of intravenous tenecteplase and the other involving thrombectomy plus intra-arterial alteplase.

In one of the studies (TNK-Plus), researchers found that intravenous tenecteplase before endovascular treatment (EVT) did not improve clinical outcomes compared with EVT alone. Yunyun Xiong, MD, PhD, et al., randomly assigned 391 patients presenting to 40 EVT-capable centers in China within 4.5 to 24 hours after stroke onset with proximal middle cerebral artery (MCA) occlusion to either intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT or EVT alone. The primary outcome of functional independence at 90 days occurred in 88 of the 197 patients (44%) in the tenecteplase group compared with 83 of the 190 patients (43%) receiving EVT alone. Mortality within 90 days was 12.7% in the tenecteplase group and 14.2% in the EVT alone group. Researchers also noted that symptomatic intracranial hemorrhage within 36 hours was 5.1% vs. 2.6%, respectively.

A second study – the INSTANT trial – found intravenous tirofiban after an inadequate response to intravenous tenecteplace increased the likelihood of improved outcomes at 90 days in patients with acute ischemic stroke without large or medium vessel occlusion or cardioembolic etiology. Trial investigators at 37 hospitals in China enrolled 359 patients (average age of 66 years, about 39% women) and assigned them to intravenous tirofiban administered as a 0.3-μg/kg/min bolus over 30 minutes, followed by a continuous infusion of 0.075 μg/kg/min for up to 47.5 hours, or matching placebo initiated within 4 to 24 hours, following intravenous tenecteplase. Oral antiplatelet therapy (aspirin and/or clopidogrel) began 24 hours after thrombolysis in the placebo group and 44 hours after thrombolysis in the tirofiban group. All patients received oral antiplatelet therapy through the 90-day follow-up.

Final results found 63.8% of participants in the tirofiban group had an excellent outcome compared with 52.2% in the placebo group. "These findings suggest a potential benefit of adjunctive intravenous tirofiban after intravenous tenecteplase in this specific patient population and warrant further investigation," said the authors.

In a third study (CHOICE-2) conducted at 14 stroke centers in Spain, Arturo Renú, MD, et al., assessed whether the adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion.

A total of 440 patients with acute ischemic stroke due to large vessel occlusion and treated with thrombectomy within 24 hours were randomized to either thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg/kg) infused over 15 minutes or thrombectomy alone. At 90 days, nearly 58% of patients in the thrombectomy plus group had an excellent outcome (defined as a modified Rank in Scale score of 0 or 1) compared with nearly 43% of patients receiving thrombectomy alone. However, researchers did note that higher mortality observed among the thrombectomy plus cohort warrants further study.