Abstract
Since the 1990s, the second-generation tissue plasminogen activator alteplase has been accepted as the gold standard in the thrombolysis of acute ischemic stroke, acute myocardial infarction, and pulmonary embolism. Alteplase, however, is not without its limitations, including a short half-life precluding single-bolus administration and elevated risk of both local and systemic bleeding. Efforts have been made to create “third-generation agents” with longer half-lives, improved fibrin specificity, and safety profiles compared to alteplase. The majority of the current Federal Drug Authority (FDA) approved third-generation agents, in particular tenecteplase and reteplase, are derivatives of alteplase. This chapter intends to compare their mechanism of action, dosing, efficacy, and safety profiles based on current evidence. Beyond tissue plasminogen activators, the chapter provides an overview of other developments in the field of fibrinolysis, including advanced drug delivery mechanisms, combination therapy, direct fibrinolysis agents, and other adjuncts.