Alteplase during PCI fails to reduce microvascular obstruction: T-TIME

  • McCartney PJ & al.
  • JAMA
  • 1 Jan 2019

  • curated by Jenny Blair, MD
  • Clinical Essentials
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  • Administering low-dose adjunctive intracoronary alteplase during percutaneous intervention (PCI) early after reperfusion of culprit vessel in ST-segment elevation myocardial infarction (STEMI) does not reduce microvascular obstruction. 
  • STRIVE and RESTORE-MI also investigate intracoronary fibrinolytics. 

Why this matters

  • 45% of patients treated for STEMI with PCI do not achieve microvascular reperfusion, owing to embolization of fibrin-rich microthrombi.
  • Microvascular obstruction predicts worse prognosis.
  • Low-dose streptokinase after primary PCI appeared to improve reperfusion in 2007 trial.
  • New fibrinolytic and antithrombotic drugs have since emerged. 

Key results

  • Recruitment halted for futility short of planned 618 participants.
  • Primary outcome:
    • 20-mg alteplase vs placebo:
      • mean, 3.5% vs 2.3%;
      • difference, 1.16%; 95% CI, −0.08% to 2.41%.
    • 10-mg alteplase vs placebo:
      • mean, 2.6% vs 2.3%;
      • difference, 0.29%; 95% CI, −0.76% to 1.35%.

Study design

  • Multicenter randomized double-blind placebo-controlled clinical T-TIME in UK (n=440). 
  • Participants underwent primary PCI within 6 hours of symptoms of STEMI from occlusion of major coronary artery.
  • Each randomly assigned to receive, after reperfusion and before stent implantation, 10 mg alteplase, 20 mg alteplase, or placebo.
  • Outcome: microvascular obstruction (% left ventricular [LV] mass) on cardiac MRI on days 2-7.
  • Funding: National Institute of Health Research (UK).


  • No long-term outcomes.

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