Downstream versus Upstream administration of P2Y12 receptor Blockers In non-ST elevated acUte coronary Syndromes with initial invasive indication - DUBIUS

Contribution To Literature:

The DUBIUS trial failed to show that a downstream P2Y12 inhibition strategy was superior to an upstream strategy in NSTE-ACS.


The goal of the trial was to evaluate downstream compared with upstream P2Y12 inhibition among patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Study Design

  • Randomized
  • Parallel
  • Open-label
  • Blocked

Eligible patients were randomized to downstream P2Y12 inhibitor (n = 721) versus upstream P2Y12 inhibitor (n = 711). In the downstream group, patients undergoing percutaneous coronary intervention (PCI) were further randomized to receive ticagrelor versus placebo.

  • Total number of enrollees: 1,432
  • Duration of follow-up: 30 days
  • Mean patient age: 65 years
  • Percentage female: 24%
  • Percentage with diabetes: 24%

Inclusion criteria:

  • Patients with NSTE-ACS undergoing coronary angiography within 72 hours

Exclusion criteria:

  • Chronic oral anticoagulation
  • Loading dose of a P2Y12 inhibitor within the last 7 days

Principal Findings:

The primary outcome, death due to vascular cause, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) 3, 4, 5 bleeding at 30 days, occurred in 2.9% of the downstream group compared with 3.3% of the upstream group (p = nonsignificant). The results were the same among those who ultimately underwent PCI.

Secondary outcomes:

  • BARC 3, 4, 5 bleeding: 1.6% of the downstream group compared with 1.9% of the upstream group
  • Definite or probable stent thrombosis: 0.1% of the downstream group compared with 0.4% of the upstream group


Among patients with NSTE-ACS, downstream P2Y12 inhibitor administration was not superior to upstream administration. Ischemic and bleeding event rates were low, and the trial was terminated early due to futility. 


Tarantini G, Mojoli M, Varbella F, et al. Timing of Oral P2Y12 Inhibitor Administration in Non-ST Elevation Acute Coronary Syndrome. J Am Coll Cardiol 2020;Aug 31:[Epub ahead of print].

Presented by Dr. Giuseppe Tarantini at the European Society of Cardiology Virtual Congress, August 31, 2020.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Anticoagulation Management and ACS, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: ESC Congress, ESC20, Acute Coronary Syndrome, Anticoagulants, Coronary Angiography, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Stents, Stroke, Thrombosis, Vascular Diseases

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