T-Time: Alteplase Infusion No Help for Failed Reperfusion in STEMI PCI

CHICAGO, IL—Low-dose coronary alteplase infused early after PCI does not reduce the likelihood of microvascular obstruction (MVO) in ST-segment elevation MI, the T-Time trial suggests.

Colin Berry, MD, PhD (University of Glasgow, Scotland), who presented the results here at the American Heart Association 2018 Scientific Sessions, explained the trial’s hypothesis: that an intracoronary thrombolytic could help improve upon rates of failed myocardial reperfusion, which occurs in up to half of all patients undergoing PCI and is independently predictive of death and heart failure long-term.

T-Time had enrolled 440 patients by the time it was stopped for futility. The study addressed patients undergoing PCI for acute STEMI due to a proximal, midvessel occlusion of a major coronary artery presenting up to 6 hours after symptom onset. Patients were randomized to either a placebo infusion or to a 10-mL or 20-mL dose of alteplase delivered after reperfusion but prior to stent implantation.

For the primary outcome of MVO on contrast-MRI between days 2 and 7 postprocedure, there was no difference between groups who underwent placebo infusion compared with the 20-mL infusion, as measured by % LV mass (2.3% vs 3.5%, P = 0.32). The 10-mL dose was associated with a slight uptick in LV mass (2.6%) as compared with placebo, suggestive of a trend in improvement for MVO by dose, but this difference, and the overall trend, were not statistically significant.

Patients who presented within 4 to 6 hours after symptoms, as compared to within 0 to 2 hours or 2 to 4 hours, had more microvascular obstruction, Berry and colleagues observed. Troponin levels were significantly higher for patients who received the 20-mL alteplase infusion and the 10-mL alteplase infusion as compared with placebo, an “unexpected” finding, Berry conceded. Repeat imaging at 3 months again found no differences between placebo and alteplase groups.

“The results do not support this therapeutic strategy, as designed,” Berry concluded. “Microvascular obstruction remains common, affecting half of all patients with STEMI, but there remains no therapy to prevent or treat this problem.”

A ‘Final Frontier’ in STEMI?

Microvascular obstruction is the “final frontier” of STEMI, Paul Armstrong, MD (University of Calgary, Canada), said when discussing the T-Time results. He noted that patient characteristics, preprocedural therapies, plus the nature and timeliness of reperfusion all have an impact on MVO.

In T-Time specifically, Armstrong highlighted a number of trial-related factors that may have influenced study outcomes, including some heterogeneity in the timing of alteplase infusion and the sequence of procedures, as well as the 30% use of thrombus aspiration, which is “not an evidence-based approach based on large-scale clinical trials.”

“All of these are potential modulators of the primary outcome,” Armstrong said. “And the adequacy and the timing of the antiplatelet therapy as well as the low use of GP IIb/IIIa inhibitors is noteworthy since, as many of the audience will recognize, the combination of fibrinolytic and GP IIb/IIIa inhibitors is very effective in producing reperfusion at both myocardial and epicardial level, regrettably with excess hemorrhage. However, with intracoronary TPA [tissue plasminogen activator], one might have achieved a different result.”

Moving forward, a better understanding of MVO and its heterogenous causes are needed, Armstrong concluded. “We need a better taxonomy associated with MVO to provide more informed solutions, and Dr. Berry and his colleagues need to be commended for helping us along this journey and directing us towards new solutions.”