One-year outcomes of a single bolus r-SAK before primary PCI for STEMI: Follow-up of the OPTIMA-5 study

The Optimal Management of Antithrombotic and Thrombolytic Agents-5 (OPTIMA-5) study demonstrated that a single bolus of half the standard dose of recombinant staphylokinase (r-SAK) before primary percutaneous coronary intervention (PCI) significantly improved the patency of the infarct-related artery in patients with ST-segment elevation myocardial infarction (STEMI), who were expected to undergo PCI within 120 min. The present study aimed to investigate the one-year clinical outcomes and the effect of the anti-r-SAK antibodies on a second r-SAK thrombolysis in OPTIMA-5 patients. The clinical outcome measured was major adverse cardiovascular events (MACE) within 360 days. Patients' anti-r-SAK antibody levels were determined on day 90 (± 7 days), day 180 (± 7 days), and day 360 (± 14 days) after thrombolysis, and in vitro r-SAK antibody neutralization experiments were performed to explore an optimal interval for a second r-SAK thrombolysis. Results showed that the MACE incidence was numerically lower in the r-SAK group compared with the normal saline (NS) group (14.0% vs. 20.0%, hazard ratio HR = 0.67, 95% confidence interval CI: 0.34–1.32; log-rank P = 0.245). The anti-r-SAK antibody levels in the r-SAK group decreased with time, but remained significantly higher than those in the NS group on day 90 (± 7 days) (2.96 ± 0.68 vs. 0.22 ± 0.53, P < 0.001), day 180 (± 7 days) (2.19 ± 0.74 vs. 0.44 ± 0.65, P < 0.001), and day 360 (± 14 days) (1.73 ± 0.97 vs. 0.37 ± 0.71, P < 0.001). The in vitro anti-r-SAK antibody neutralization experiments demonstrated that the thrombolysis rate decreased exponentially as the antibody titer increased from 1.90 to 2.20 (67.80% ± 14.19% vs. 44.32% ± 21.54%, P < 0.0001). Therefore, for STEMI patients who are expected to undergo PCI within 120 min, a single bolus of half-dose r-SAK before primary PCI may reduce the one-year MACE risk. The anti-r-SAK antibody persists over one year, and a second r-SAK thrombolysis may not be indicated until at least one year after the first administration, if necessary.