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.

Description:

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

Interpretation:

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. 

References:

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.

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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