Thrombolytic strategies for ischemic stroke in the thrombectomy era

Twenty-five years ago, intravenous thrombolysis has revolutionized the care of patients with acute ischemic stroke. Since 2015, randomized clinical trials have demonstrated that mechanical thrombectomy improves functional outcome in stroke patients over intravenous thrombolysis alone. More recently, three randomized clinical trials have suggested that mechanical thrombectomy alone is noninferior to a combined strategy with both intravenous thrombolysis and mechanical thrombectomy. In the present review, we will present the last clinical and preclinical studies on the use of thrombolysis in stroke patients in the modern thrombectomy era. At the cost of a potential increased risk of hemorrhagic transformation, thrombolysis may promote arterial recanalization before thrombectomy, improve the rate of successful recanalization after thrombectomy, and restore microcirculation patency downstream of the main thrombus. Besides, new thrombolytic strategies targeting tissue-type plasminogen activator resistant thrombi are being developed, which could strengthen the beneficial effects of thrombolysis without carrying additional pro-hemorrhagic effects. For instance, tenecteplase has shown improved rate of recanalization compared with tissue-type plasminogen activator (alteplase). Beyond fibrinolysis, DNA- and von Willebrand factor-targeted thrombolytic strategies have shown promising results in experimental models of ischemic stroke. New combined strategies, improved thrombolytics, and dedicated clinical trials in selected patients are eagerly awaited to further improve functional outcome in stroke.