Clinical development of PEGylated recombinant staphylokinase (PEG–Sak) for bolus thrombolytic treatment of patients with acute myocardial infarction

The development of bolus thrombolytic agents, in conjunction with bolus anti-thrombotics (e.g. low molecular weight heparins), remains an ambitious but achievable goal of therapy for acute myocardial infarction—a disease which takes the lives of millions each year. This chapter summarizes the data accumulated over nearly a decade of investigation of recombinant staphylokinase (Sak) as a safe, cost-effective thrombolytic agent. The results of extensive animal investigations suggested this agent exhibited a uniquely fibrin-selective mechanism of action. Administration of various recombinant versions of the molecule to over 1000 patients on a global scale suggest this agent may be as effective as tissue-type plasminogen activator (rt-PA) in achieving prompt arterial recanalization of acutely occluded coronary arteries. The development of this protein as a single bolus agent is described in detail, and the results of recently completed international trials comparing this bolus agent to front-loaded rt-PA are summarized.