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Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study
Giuseppe Tarantini1, Marco Mojoli2, Ferdinando Varbella3
1Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, Policlinico Universitario, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. giuseppe.tarantini.1@gmail.com.
Background:
The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors-ticagrelor and prasugrel-currently recommended by the guidelines.
Study Design:
DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings.
Conclusions:
The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed.
Trial Registration:
ClinicalTrials.gov NCT02618837 . Registered on 1 December 2015.
Insights
The DUBIUS study compares early ticagrelor pretreatment versus later administration in non-ST-elevation acute coronary syndrome (NSTE-ACS) patients. It also compares downstream prasugrel with downstream ticagrelor for optimal P2Y12 inhibitor therapy.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Optimal timing for P2Y12 inhibitor administration in non-ST-elevation acute coronary syndrome (NSTE-ACS) is debated.
- Pretreatment with ticagrelor is common, but evidence comparing it to downstream administration is limited.
- Head-to-head comparisons between ticagrelor and prasugrel are also scarce.
Purpose of the Study:
- To compare a pretreatment strategy (ticagrelor) versus a downstream strategy (ticagrelor or prasugrel) in NSTE-ACS patients.
- To compare downstream prasugrel with downstream ticagrelor.
- To evaluate the efficacy and safety of different P2Y12 inhibitor administration timings and agents.
Main Methods:
- Phase 4, multicenter, double randomized study (DUBIUS) in 2520 NSTE-ACS patients.
- Patients randomized to ticagrelor pretreatment or no pretreatment.
- Downstream arm patients randomized to prasugrel or ticagrelor after percutaneous coronary intervention (PCI).
Main Results:
- Primary hypotheses: downstream strategy superiority over upstream, and non-inferiority of downstream ticagrelor to downstream prasugrel.
- Composite endpoint: death from vascular causes, non-fatal MI, non-fatal stroke, or Bleeding Academic Research Consortium (BARC) types 3, 4, or 5 bleeding.
- Study results will inform optimal P2Y12 inhibitor use in NSTE-ACS.
Conclusions:
- The DUBIUS study will provide evidence on ticagrelor pretreatment benefits and risks.
- It will assess the clinical impact of downstream ticagrelor versus downstream prasugrel.
- Findings will guide clinical practice regarding P2Y12 inhibitor timing and choice in NSTE-ACS.
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