Results from STRIVE Announced at TCT 2025 and Published Simultaneously in JACC
SAN FRANCISCO – OCTOBER 28, 2025 – Results from the multicenter, randomized, double-blind, placebo-controlled STRIVE trial found that low doses of recombinant tPA (alteplase) in patients with large-territory STEMI and high thrombus burden undergoing primary percutaneous coronary intervention (PCI) did not improve outcomes.
Findings were reported today at TCT® 2025, the annual scientific symposium of the Cardiovascular Research Foundation® (CRF®) and published in the Journal of the American College of Cardiology. TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.
Approximately one-half of patients with apparently successful primary PCI for STEMI have distal embolization of thrombus causing coronary microvascular obstruction and reduced myocardial tissue perfusion. This leads to larger infarct size and higher rates of heart failure, cardiogenic shock and mortality. The STRIVE trial evaluated a novel strategy to prevent and treat microvascular obstruction and reduce major cardiovascular events by delivering alteplase, a fibrin-specific thrombolytic, directly into the culprit coronary artery.
Patients who presented with STEMI within six hours of symptom onset and were referred for primary PCI were eligible for the study. All patients were required to have evidence of large territory STEMI on the qualifying ECG and evidence of large thrombus burden on coronary angiography. A total of 210 patients were randomly assigned to receive the study drug or placebo (68 received alteplase 10 mg, 69 received alteplase 20 mg and 70 were given placebo). After antegrade flow was established, a delivery catheter was inserted into the infarct-related artery distal to the culprit lesion and the study drug was infused over three minutes. Primary PCI was then performed per standard practice.
The primary outcome was the composite of MACE at 30 days, TIMI myocardial blush grade 0/1, distal embolization or failure to achieve 50% ST segment resolution at 30 minutes post-PCI. MACE included the first occurrence of cardiovascular death, re-MI, cardiogenic shock and new onset heart failure at 30 days. The primary safety outcomes were major bleeding or the composite of major bleeding or clinically relevant bleeding at 30 days. The primary outcome occurred in 73 patients (53.3%) in the combined alteplase groups versus 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 versus placebo. Major or clinically significant bleeding occurred in one patient in the trial (in the alteplase 20 mg group). During study drug administration, there were more episodes of ventricular fibrillation in the alteplase groups compared to the placebo group (10.2% vs 1.4%, relative risk 6.86, 95% CI 0.91-51.4, P=0.06).
“Microvascular obstruction after primary PCI remains the single most important unresolved issue limiting the efficacy of primary PCI in STEMI patients,” said Shamir R. Mehta, MD, MSc, Douglas A. Holder Endowed Chair, Professor of Medicine at McMaster University; Director, Interventional Cardiology at Hamilton Health Sciences and Senior Scientist at the Population Health Research Institute. “STRIVE does not support the routine administration of alteplase and it joins the growing list of previously promising therapies that have not succeeded in improving this important issue.”
The study was funded by the Heart and Stroke Foundation of Canada.
Dr. Mehta reported receiving institutional research grants from Abbott and has done consulting work for Abbott, Amgen, Janssen, Novartis and NovoNordisk. He is also on the Data Monitoring Committee for a Merck-sponsored trial.
