STRIVE: Low-Dose Alteplase Ineffective in STEMI Patients With Large Thrombus

SAN FRANCISCO, CA—Administering low-dose alteplase directly into the artery prior to PCI in patients with STEMI and a large thrombus burden fails to lower the risk of a range of outcomes, including microvascular perfusion and MACE, when compared with a saline solution, according to results from the STRIVE trial.

The intracoronary fibrinolysis infusion joins a number of other adjunctive therapies, including mechanical thrombectomy, that have failed to reduce microvascular obstruction and improve clinical outcomes in this context.

“We could not have any more of a neutral result,” said lead investigator Shamir Mehta, MD (McMaster University/Hamilton General Hospital, Canada), during a press conference at TCT 2025 where the results were announced. “Regardless of how you look at microvascular obstruction, whether you look at it angiographically with myocardial blush grade or whether you look at it with ST-segment resolution at 30 minutes, it is completely neutral.”

Presentation TCT 2025

Effects of Intracoronary Low-Dose Recombinant Tissue Plasminogen Activator as an Adjunct to Primary PCI in Patients with STEMI and Large Thrombus Burden: A Randomized, Double-Blind, Placebo-Controlled Trial

That neutral result was seen across all predefined subgroups, said Mehta.

“It didn’t matter how early or late a patient presented,” he continued. “We saw it in men and women. We saw it with anterior and large inferior STEMIs. We saw it regardless of the initial flow in the artery and regardless of the flow right before we administered the study drug. The results are completely consistent.”

Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), who moderated the press conference, said the field continues to search for a therapy that could improve downstream circulation in STEMI patients with a high thrombus burden. As an interventional cardiologist who cares for such patients, he expressed disappointment in the findings.

“Every time we see a trial of something that seems promising for microvascular disease, and then I hear a presentation like [STRIVE], I just want to say a four-letter word. It’s like, man, really?”

The results of STRIVE are quite definitive. They do not support this therapy. Shamir Mehta

Francesco Costa, MD, PhD (University of Malaga, Spain), said STRIVE was a “rock solid” trial with extremely clear results. These findings, he added, mirror T-TIME, the other study that showed no benefit of adjunctive fibrinolytic therapy in STEMI patients.

Costa said the results close the door on any thoughts of routinely using intracoronary fibrinolytic therapy in patients with a large thrombus burden but suggested there might be other avenues for testing. For example, delivering the infusion after the stent is implanted is currently being investigated, a strategy that might theoretically improve drug delivery to the microvasculature, said Costa. 

Many Have Tried, None Succeeded

The study, presented as a late-breaking clinical trial and published simultaneously in JACC, was designed to address a common problem in STEMI, said Mehta. Up to half of patients who present have microvascular obstruction resulting from the distal embolization of thrombus. This can lead to a larger infarct size and higher risks of heart failure, cardiogenic shock, and mortality.

“Over the last couple of decades, there have been many therapies that have tried to improve microvascular obstruction,” said Mehta.

These have included trials of mechanical thrombectomy and intracoronary administration of glycoprotein IIb/IIIa inhibitors. Facilitated PCI with a fibrinolytic delivered systemically was associated with a higher bleeding risk and didn’t improve outcomes either.

The approach used in STRIVE differed: operators administered low-dose alteplase, which is a fibrin-specific thrombolytic with a short half-life, into the infarct-related artery via a delivery catheter. The rationale was to directly target the thrombus in the microcirculation at a reduced dose—roughly 12% of the systemic dose—to avoid the bleeding complications seen with systemic administration.

Patients with a large-territory STEMI and high thrombus burden undergoing primary PCI were randomized to one of three treatment arms: 69 patients to intracoronary alteplase 10 mg, 70 patients to a 20-mg dose, and 71 to a placebo group. After antegrade flow was established, the study drug was infused over 3 minutes and then followed by standard-protocol primary PCI.

At 30 days, the primary endpoint—a composite of MACE, TIMI myocardial blush grade 0/1, distal embolization, and failure to achieve ≥ 50% ST-segment resolution at 30 minutes post-PCI—occurred at a rate of 53.3% in the alteplase arm and 52.9% in the placebo arm (RR 1.00; 95% CI 0.76-1.31). There was no benefit with 10-mg or 20-mg doses when compared with placebo alone. When the primary endpoint was analyzed by components, there was no significant treatment effect with low-dose alteplase.

Ventricular fibrillation was more common in the alteplase-treated patients (14 events versus one in the placebo group; P = 0.06). Major bleeding and clinically relevant nonmajor bleeding rates were no different with alteplase versus placebo.  

“The results of STRIVE are quite definitive,” said Mehta. “They do not support this therapy.”

David Cohen, MD (St. Francis Hospital & Heart Center, Roslyn, NY, and Cardiovascular Research Foundation, New York, NY), who moderated the late-breaking trial session, said it may be that the hypothesis that thrombus is involved in microvascular obstruction is off the mark.

“Is it possible,” he suggested, “that it’s not the drug or the side effects but that we’re just tackling the wrong target?”

Mehta agreed, saying microvascular dysfunction may be more complex than currently understood. “It might not be possible to have such a simple concept of giving a lytic and expecting the microvasculature would open,” said Mehta. Nonetheless, he hopes that the field doesn’t give up studying this issue. “If we can solve this problem for primary PCI,” Mehta noted, “we can save a lot more lives, no question, both in the short and the long term.”