Trial of Low-Dose Adjunctive Alteplase During Primary PCI - T-TIME

Contribution To Literature:

Adjunctive low-dose alteplase at the time of primary PCI among patients presenting with STEMI did not reduce the incidence of microvascular obstruction on MRI.


The goal of the trial was to assess the safety and efficacy of low-dose alteplase in reducing microvascular obstruction among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Study Design

Eligible patients were randomized in a 1:1:1 fashion to alteplase 10 mg (n = 144), alteplase 20 mg (n = 145), or placebo (n = 151). This was administered as a manual intracoronary infusion over 5–10 minutes. The intervention was scheduled to occur early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery, and before stent implantation.

  • Total number of enrollees: 440
  • Duration of follow-up: 3 months
  • Mean patient age: 60.5 years
  • Percentage female: 15%

Inclusion criteria:

  • Age ≥18 years
  • Acute MI (symptom onset ≤6 hours) with persistent ST-segment elevation or recent left bundle branch block
  • Coronary artery occlusion (TIMI coronary flow grade 0 or 1) OR impaired coronary flow (TIMI flow grade 2, slow but complete filling) in the presence of definite angiographic evidence of thrombus (TIMI grade 2+)
  • Proximal-mid culprit lesion location in a major coronary artery (i.e., the right, left anterior descending, intermediate or circumflex coronary artery)
  • Radial artery access

Exclusion criteria:

  • Shock
  • Normal coronary flow grade (TIMI flow grade 3) at initial angiography
  • Functional coronary collateral supply to culprit artery
  • Multivessel PCI intended before the day 2-7 magnetic resonance imaging (MRI) scan
  • Noncardiac comorbidity with expected survival <1 year
  • Estimated body weight <60 kg
  • Contraindication to contrast-enhanced MRI
  • Previous infarction in the culprit artery (known or suspected clinically, e.g., wall motion abnormality revealed by echocardiography)
  • Bleeding diathesis

Other salient features/characteristics:

  • Anterior infarct: 44%
  • Prior MI: 5%
  • Symptom onset to perfusion: 220 minutes
  • TIMI 0 flow on initial angiography: 82%
  • Aspiration thrombectomy: 30%, balloon angioplasty: 71%
  • Use of ticagrelor or prasugrel: 53%

Principal Findings:

The trial was stopped early due to futility. The primary outcome, amount of microvascular obstruction as % of left ventricular mass, for alteplase 10 mg vs. alteplase 20 mg vs. placebo, was 2.6% vs. 3.5% vs. 2.3%, p > 0.05.

Secondary outcomes: 

  • Troponin area under the curve (AUC) higher for both alteplase doses compared with placebo: relative risk 1.53, 95% confidence interval 1.16-2.01, p = 0.002
  • Major adverse cardiac events: 12.9% vs. 8.2% vs. 10.1%, p = 0.43
  • TIMI myocardial perfusion grade 0/1: 44.5% vs. 40.0% vs. 37.8%
  • Major bleeding: 0.7% vs. 0.7% vs. 0%, p = 0.55


The results of this trial indicate that adjunctive low-dose alteplase at the time of primary PCI among patients presenting with STEMI did not reduce the incidence of microvascular obstruction on MRI and resulted in larger MIs, as evidenced by a higher AUC for troponin. Microvascular obstruction is common after STEMI and no single intervention has been shown to have a convincing benefit.


McCartney PJ, Eteiba H, Maznyczka AM, et al., on behalf of the T-TIME Group. Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA 2019;321:56-68.

Presented by Dr. Colin Berry at the American Heart Association Annual Scientific Sessions (AHA 2018), Chicago, IL, November 11, 2018.

Keywords: AHA Annual Scientific Sessions, AHA18, Acute Coronary Syndrome, Bundle-Branch Block, Coronary Occlusion, Fibrinolysis, Magnetic Resonance Imaging, Myocardial Infarction, Percutaneous Coronary Intervention, Stents, Thrombosis, Tissue Plasminogen Activator

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