5232Inhibition of platelet aggregation after subcutaneous administration of a single-dose of selatogrel, a novel P2Y12 antagonist, in acute myocardial infarction: a randomised open-label phase 2 study

Abstract Background Oral P2Y12 receptor antagonists exhibit a delayed onset of platelet inhibition in patients experiencing acute myocardial infarction (AMI). Selatogrel is a potent, reversible, and highly selective P2Y12 receptor antagonist with a rapid onset and offset of action when administered subcutaneously. Purpose To assess inhibition of platelet aggregation (IPA) after subcutaneous (s.c.) single-dose administration of selatogrel in patients with AMI receiving standard concomitant therapy. Methods Male and postmenopausal female adults (≤85 years) presenting with type 1 AMI (ST-elevation MI [STEMI] or non-STEMI [NSTEMI]) and onset of AMI symptoms &gt;30 min to &lt;6 h were randomised (1:1) to receive a single s.c. dose of either 8 mg or 16 mg selatogrel. Blood samples were collected at baseline and at 15, 30, and 60 min post-dose and evaluated for ADP-induced platelet aggregation (expressed as P2Y12 reaction units [PRU]) using VerifyNow. The primary endpoint was the response to treatment (defined by PRU &lt;100) at 30 min post-dose. Safety was assessed up to 48 h post-dose. Results Forty-seven patients (median age 69 y; 72% male; 62% STEMI; 94% Killip class 1) received 8 mg (N=24) or 16 mg (N=23) selatogrel. Study-treatment concomitant medications included acetylsalicylic acid (98%), P2Y12 inhibitors (96%), heparins (94%), statins (94%), nitrates (68%) and morphine (38%). Oral ticagrelor (92%) with corresponding loading doses was only administered after selatogrel. The proportion of patients meeting the primary endpoint (responders) 30 min post-dose was 91% (95% CI: 72, 99) and 95% (95% CI: 77, 100) with 8 and 16 mg, respectively (p&lt;0.001 for both doses). Response rates were independent from STEMI/NSTEMI diagnosis, age and sex. A response was observed as early as 15 min (8 mg: 75% of patients [95% CI: 53, 90]; 16 mg: 91% of patients [95% CI: 72, 99]), and sustained up to 60 min post-dose (8 mg: 75% of patients [95% CI: 53, 90]; 16 mg: 96% of patients [95% CI: 78, 100]). Platelet reactivity was decreased following selatogrel administration (Figure; interquartile range [box], min and max [whiskers], median and mean [horizontal line and symbol, respectively, within the box]). Overall, 43% of patients had ≥1 treatment-emergent adverse event (TEAE), which were mainly of mild/moderate intensity. Ventricular tachycardia ([VT] 8 mg: 5/24; 16 mg: 3/23) was the most frequent TEAE. Treatment-emergent serious AEs of VT were reported in two patients receiving 8 mg (one patient also experienced ventricular fibrillation) and one patient receiving 16 mg selatogrel. Post-procedural haemorrhage (mild) occurred in one patient: bleeding at radial access after percutaneous coronary intervention (∼1 h after selatogrel 8 mg). Conclusion Single-dose administration of s.c. selatogrel (8 mg and 16 mg) induced a rapid IPA response in patients with AMI at 30 min (as early as 15 min and maintained at 60 min post-dose) and was well-tolerated with no major bleeding events. Acknowledgement/Funding Fully funded by Idorsia Pharmaceuticals Ltd </jats:sec

Management, research and budgetting of aggregates in shelf seas related to end-users (Marebasse)

Sustainable management of the Belgian exclusive economic zone (EEZ) has become important increasingly. This is due mainly to higher exploitation demands of marine aggregates, but also the dredging industry imposes high stresses on the seafloor. To anticipate on future developments, including the implantation of windmill farms, efficient evaluation tools and strategies of seabed nature and dynamics are needed, based on the best available science.A three-tiered approach was followed, corresponding to three spatial scales: broad-based, regional and site-specific. On the scale of the Belgian part of the North Sea (BPNS), sediment transport models were further developed to evaluate large-scale sedimentary processes and to provide a baseline for any detailed investigation. On a regional scale, evaluation tools and strategies were developed within the view of the optimisation of environmental (impact) assessments. New site investigations integrated results from state-of-the-art geo-acoustical and terrain verification tools and from a multisensor benthic lander, equipped with hydrodynamic and sediment transport instrumentation. To assess the environmental impact of aggregate extraction, multidisciplinary research was carried through national and international cooperation. Knowledge was integrated on the physical, geomorphological, sedimentological and biological nature of the seafloor. Valorisation of the results comprised a series of thematic maps on the nature and dynamics of the BPNS and a suite of recommendations on sustainable management and exploitation of the EEZ. The latter include criteria to select most appropriate locations for aggregate extraction and dredging/dumping operations whilst minimising environmental effects. However, sustainability can be ensured only if good management/policy practices are in place and implemented in a structural way

Adapting to Climate Change in Urban Water Management: Flood Management in the Rotterdam–Rijnmond Area

Many large coastal cities are located in deltas, which makes them vulnerable to floods. In many cities flood damage has increased due to increases in population and assets, and this process is expected to continue. At the same time, climate change will cause floods to occur more often in many rivers and deltas due to higher discharges and sea level rise. These trends call for the development and implementation of new technologies and strategies in flood risk management. This call is also acknowledged in the Netherlands, a country that has a strong history of relying on structural measures. The city of Rotterdam includes many unembanked areas, large parts of which will be redeveloped in the near future. Current practice is to elevate all unembanked areas to a 1 in 4,000 years flood level. This is not only very costly, but also causes problems when an area is redeveloped in phases, or when existing buildings will remain as both cause unwanted elevation differences and differences in flood protection. Rotterdam is therefore looking for adaptive (non-structural) measures to decrease flood damage in these areas. Such measures are presently little used in the Netherlands. One key question is how these new measures fit in within current policies, laws, and regulations in Rotterdam. This chapter describes measures studied for a case study area in Rotterdam, gives an analysis of the policies, laws, and regulations relating to these measures, and examines the implications for urban flood management. Our research shows that, in principle, the rules do allow for implementation of adaptive measures. It is, however, problematic how these measures can be enforced, and this weakness can cause problems, e.g. when not all waterfront buildings are dry-proofed. Better communication of flood risks is recommended, as this will increase awareness and preparedness, which in turn might lead to a higher implementation rate of adaptive measures.</p