Antithrombotic Effects of Montelukast by Targeting Coagulation Factor XIa

Current oral anticoagulants prescribed for the prevention of thrombosis suffer from severe hemorrhagic problems. Coagulation factor XIa (FXIa) has been confirmed as a safer antithrombotic target as intervention with FXIa causes lower hemorrhagic risks. In this study, by a high-throughput virtual screening, we identified Montelukast (MK), an oral antiasthmatic drug, as a potent and specific FXIa inhibitor (IC50 = 0.17 µM). Compared with the two mostly prescribed anticoagulants (Warfarin and Apixaban), MK demonstrated comparable or even higher antithrombotic effects in three independent animal models. More importantly, in contrast to the severe hemorrhage caused by Warfarin or Apixaban, MK did not measurably increase blood loss in vivo. In addition, MK did not affect the hemostatic function in plasma from healthy individuals. In contrast, MK suppressed clot formation in clinical hypercoagulable plasma samples. This study provides a lead compound of anticoagulants targeting FXIa, and suggests the exploratory clinical researches on antithrombotic therapies using MK.

P47 Prevalence, incidence and patterns of antiasthma medication use in children: a nationwide prescription study in France

BackgroundUse of antiasthmatic medications has increased over the years worldwide. The aim of this study was to describe the use of antiasthmatic drugs in children in France.MethodsData were retrieved from the permanent sample (1/97th) of the French national healthcare database - the Système National des Données de Santé (SNDS) for all individuals aged from 5 to 18 years old (n=143,909) from 1 January 2011 to 31 December 2017. Prevalence and incidence rate of antiasthmatic dispensing were calculated. All analyses were stratified by calendar year, age (5–11, 12–18 years) and gender. Users were classified as occasional if they had only one dispensing of antiasthmatic drugs over the year, moderate and high if they had antiasthmatic drug dispensing at two distinct occasions or at three or more occasions, respectively.ResultsThe annual prevalence of antiasthmatic drug use varied between 12 (2011) and 11 (2017) per 100 persons and incidence varied between 4.3 (2013) and 3.8 (2017) per 100 PYs. Prevalence and incidence of use were higher in children aged between 5–11 years compared to adolescents and in boys compared to girls. Most users were occasional (52%) and only one third redeemed prescriptions on a regular basis (high users: 30%). No trend was observed regarding these percentages over time or with gender and age group.ConclusionsUse of antiasthmatic drugs in France is higher than previously described in other European countries. Prevalence of use is also higher than the prevalence of asthma as assessed in epidemiological national studies suggesting that these drugs are over-prescribed.Disclosure(s)Nothing to disclose

Spirometry monitoring in asthmatic children in Lombardy Region, Italy

ObjectivesTo evaluate the diagnostic and therapeutic approaches in a cohort of asthmatic children before and after starting drug therapy.MethodsData were retrieved from administrative databases of the Lombardy Region. The study population was composed of 78 184 children born in the Lombardy Region in 2002 and followed until their 10th birthday.Children with at least one antiasthmatic drug prescription per year (with the exclusion of nebulised suspension/solution formulations) in 2 consecutive years and at least one antiasthmatic drug prescription after the fifth birthday were identified as potential asthmatics (PA).Each PA was monitored for a period starting from 12 months before and ending 24 months after the first prescription (index prescription, IP). During the monitoring period antiasthmatic drug prescriptions were analysed, as well as spirometry and/or specialist visits.ResultsA total of 59 975 children (76.7%) received ≥1 prescription of antiasthmatic drugs in their first 10 years of life, and 4475 (5.7%) were identified as PAs. In all, 24% of PAs started with short-acting β2-agonists (SABA), 23% with inhaled corticosteroids (ICS) and 20% with SABA+ICS.A total of 33% of PAs had at least one prescription for specialist visit/spirometry: 11% before and 28% after the IP. The factors associated with a greater likelihood of receiving visit/spirometry prescriptions were local health unit of residence, age and high use of asthma drugs.ConclusionsDespite international guideline recommendations, spirometry monitoring is still underused in asthmatic children, even in subjects who initiated pharmacological treatment and therefore need an airway function evaluation. Moreover, the choice of drug therapy appears not always rational, since one out of four children were commenced on ICS as monotherapy.