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Background: Although oral P2Y 12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined., Objectives: The purpose of this study was to compare downstream and upstream oral P2Y 12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment., Methods: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit)., Results: We randomized 1,449 patients to downstream or upstream oral P2Y 12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment)., Conclusions: Downstream and upstream oral P2Y 12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y 12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837)., Competing Interests: Author Relationship With Industry This work was funded by the Italian Society of Interventional Cardiology (SICI-GISE). Dr. Tarantini has received Speakers Bureau fees from AstraZeneca, Daiichi-Sankyo, and Eli Lilly. Dr. Mojoli has received individual payments for participating on the Advisory Boards of The Medicines Company and Abbott Vascular; and has been a speaker at scientific congresses from AstraZeneca, Daiichi-Sankyo, Chiesi Farmaceutici, and Servier; and his institution has received an unconditioned research grant from Chiesi Farmaceutici. Dr. Varbella has received consulting fees/honoraria from AstraZeneca, Daiichi-Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Servier, Amgen, Sanofi, Piam, Alvi Medica, Teleflex, and Stenty. Dr. Caporale has received an Advisory Board fee from AstraZeneca. Dr. Rigattieri has received a consulting fee from AstraZeneca; and has received a Speakers Bureau fee from Eli Lilly. Dr. Andò has received individual payments as a consultant, for serving on the Advisory Board, or as a speaker at scientific congresses from AstraZeneca, Daiichi-Sankyo, Chiesi Farmaceutici, Pfizer–Bristol Myers Squibb, Boehringer Ingelheim, and Biosensors. Dr. Saia has received Speakers Bureau fees from AstraZeneca and Daiichi-Sankyo. Dr. Ferlini has received individual payment as a consultant, for serving on the Advisory Board, or as a speaker at scientific congresses from AstraZeneca, Chiesi Farmaceutici, Bayer, Biosensors, Sanofi, and Boehringer Ingelheim. Dr. Angiolillo has received consulting fees or honoraria as an individual from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payment as an individual for participation in review activities from CeloNova and St. Jude Medical; and has received institutional payments for grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli-Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

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.

With the ageing of the population in the Western world, an increasing proportion of patients seen in cardiology practice is represented by the elderly. Although approximately one third of patients admitted with acute coronary syndrome (ACS) are >75 years old and the mortality rate in this age group is doubled compared with younger patients, this population is underrepresented in randomized controlled trials and, consequently, clinical guidelines do not always provide clear indications for the management of elderly patients. Therefore, there is an unmet need for clinical guidance regarding this rapidly growing subset of ACS patients, also considering that decisions about optimal antithrombotic treatment strategies in the elderly are often challenging, mostly due to age-related organ dysfunction, the frequency of comorbidities and concomitant medications and an increased risk of both ischemic and bleeding events. A panel of Italian cardiology experts assembled under the auspices of the Italian Society of Interventional Cardiology (SICI-GISE) for comprehensive discussion and consensus development, with the aim to provide practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of antithrombotic therapy in patients with ACS aged ≥75 years. In this position paper, various clinical scenarios in patients with ST-elevation and non-ST-elevation myocardial infarction or unstable angina are presented and discussed, including special subsets (e.g., patients aged ≥85 years, patients with chronic renal disease or previous cerebrovascular events, patients requiring triple therapy or long-term antithrombotic therapy), with the panel's recommendations being provided for each scenario.

A 69-year-old female was hospitalized for acute coronary syndrome and received full antiplatelet and anticoagulant therapy. The patient underwent angioplasty and stent implantation on right coronary and left circumflex arteries with good angiographic result. After the procedure, the patient developed hemorrhagic shock due to massive left renal hemorrhage. An emergent digital subtraction angiography showed bleeding from a left segmental renal artery. The hemorrhage was successfully managed with transcatheter superselective embolization. The patient was discharged after 22 days in good general condition with normal renal function. One-year follow-up was uneventful.