Intracoronary Low-Dose Recombinant Tissue Plasminogen Activator in Primary PCI for ST-Segment Elevation Myocardial Infarction and Large Thrombus Burden: A Randomized Trial.

BACKGROUND

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), approximately one-half of patients experience distal embolization of thrombus causing microvascular obstruction and reduced myocardial tissue perfusion. Targeted, intracoronary delivery of low-dose recombinant tissue plasminogen activator (alteplase) might be an effective strategy for improving microvascular obstruction without increasing the risk of systemic bleeding.

OBJECTIVES

This study aims to determine whether adjunctive intracoronary delivery of low-dose alteplase reduces microvascular obstruction or major adverse cardiac events (MACE) in patients undergoing primary PCI for STEMI and high thrombus burden.

METHODS

We performed a multicenter, randomized, double-blind trial involving patients undergoing primary PCI for large territory STEMI and high thrombus burden. Patients were randomized to receive either alteplase 10 mg, alteplase 20 mg, or placebo (saline) administered directly into the infarct-related artery using a delivery catheter after antegrade reperfusion was established. The primary outcome was the composite of MACE, myocardial blush grade 0/1, distal embolization, or failure to achieve ≥50% ST-segment resolution at 30 minutes post-PCI. MACE was the composite of cardiovascular death, myocardial re-infarction, cardiogenic shock, or new-onset heart failure at 30 days.

RESULTS

Of 210 patients who were randomized, 207 received study drug (n = 68 alteplase 10 mg, n = 69 alteplase 20 mg, and n = 70 placebo). The mean age was 62.6 years and 25% were female. The median time from symptom onset to randomization was 2.9 hours. The primary outcome occurred in 73 patients (53.3%) in the combined alteplase groups vs 37 (52.9%) in the placebo group (relative risk: 1.00; 95% CI: 0.76-1.31; P > 0.99). Results were consistent across all components of the primary outcome and for each dose group vs placebo. Major or clinically significant bleeding occurred in 1 patient in the trial (in the alteplase 20 mg group). During study drug administration, there was a trend to more episodes of ventricular fibrillation in the alteplase groups compared with the placebo group (10.2% vs 1.4%, relative risk: 6.86; 95% CI: 0.91-51.4; P = 0.06).

CONCLUSIONS

Among patients undergoing primary PCI for STEMI and large thrombus burden, intracoronary administration of alteplase was not superior to placebo in reducing the composite primary outcome of MACE at 30 days, myocardial blush grade 0/1, distal embolization, or failure to achieve ≥50% ST-segment resolution. These data do not support the routine administration of this therapy in patients with STEMI undergoing primary PCI (STRIVE [Adjunctive, Low-dose tPA in Primary PCI for STEMI]; clinicaltrials.gov NCT03335839).