Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: rationale and design of the LEGACY study

BackgroundEarly aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI.MethodsThe LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT.ConclusionsThe LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.Cardiolog

Investigation of Metal and Non-Metal Doped Dimer and Trimer C-60 Fullerene Chains as Prospective Spin Cluster Qubits

We have calculated the optimized geometries, electronic structures and spin distributions of metal and non-metal elements Li, Na, N and P doped C60 fullerene dimers and trimers with different spin multiplicities using hybrid density functional theory (DFT) at the B3LYP/6-31G level of theory. Natural population analysis and Mulliken population analysis show that non-metal elements (N, P) inside the C60 fullerene dimers and trimers are well isolated and preserve their electronic structures while charge transfer processes occur between metal elements (Li, Na) and C60 structures. Energy calculations showed that both doped and undoped linear C60 structures are energetically lower than triangular C60 structures. Calculated spin density distributions make non-metal doped C60 structures advantageous over metal doped C60 cases as spin cluster qubits

The Application of Integrated Logistic Support Concepts in Energy Project Planning

With the increase in size, cost and strategic importance of energy projects, a structured approach to planning, design, construction and operation is required. Integrated Logistic Support (ILS) is a management concept providing controls to help ensure that a system will meet its performance requirements and receive effective and economical support throughout its life cycle. A major ILS objective is to ensure the integration within the design process of the various support elements. Techniques enabling the identification of critical areas of deficiency along with some examples are presented

Impact of age on the comparison between short-term vs 12-month dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-Year follow-up results of the REDUCE trial

BACKGROUND AND AIMS: The impact of advanced age on the optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary revascularization (PCI) is still greatly debated. Therefore, the aim of the present sub-analysis of the REDUCE trial was to assess the impact of age on the comparison between a short 3 months vs standard 12 months DAPT in ACS patients treated with the COMBO Dual Stent Therapy. METHODS: The REDUCE trial is a prospective, multicenter, investigator-initiated study that randomized ACS patients undergoing PCI with the COMBO drug eluting stent to either 3 or 12 months of DAPT. The study population was divided according to age (<or ≥ 75 years). Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleeding (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016, 1496 patients were included in the study, of whom 205 (13.7%) ≥75 years of age. Among them, 50.7% of the elderly and 50.2% of younger patients were assigned to the 3-month DAPT treatment. Baseline characteristics were well matched between the two arms, except for a higher rate of males (p=0.02) and a reduced number of lesions on the right coronary artery (p=0.02) in elderly patients treated for the short DAPT duration. Median follow-up was 682.5 days [IQR:667-731]. At 12 months, no difference in the primary endpoint was observed according to DAPT duration in both patients aged ≥75 years (22.1% vs 18.8%, HR [95%CI] = 1.6 [0.73-3.5], p=0.24) and younger ones (9.7% vs 10.9%, HR [95%CI] = 0.85 [0.59-1.27], p=0.44; p INT = 0.15). Results were confirmed after correction for baseline differences among the elderly (adjusted HR [95%CI] = 1.7 [0.75-3.9], p=0.21). Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of age. CONCLUSIONS: The present study shows that among ACS patients randomized in the REDUCE trial, a 3-month DAPT strategy was comparable to a standard 12-month DAPT at a 2-year follow-up for both ischemic and bleeding endpoints, in elderly and younger patients. Thus, despite presenting the limitations of a subgroup analysis, our study strengthens the feasibility of a shorter DAPT duration even among high-risk subsets of ACS patients