A pharmacokinetic and pharmacodynamic evaluation of asundexian: a novel factor XIa inhibitor for stroke prevention.

INTRODUCTION: Antithrombotic therapy is the mainstay of ischemic stroke prevention. Current drugs (antiplatelets and oral anticoagulants) lead to increased bleeding risks, and the rates of stroke recurrence, despite antithrombotic therapy, are still elevated. There is a need for novel antithrombotic therapies with superior effectiveness but without increased bleeding risk. Factor XIa inhibitors might cover this gap. AREAS COVERED: This manuscript examines the pharmacokinetic and pharmacodynamic properties of asundexian and the current clinical evidence regarding its application in preventing ischemic stroke. EXPERT OPINION: Asundexian shows a very favoring pharmacokinetic profile. Despite asundexian being inferior to apixaban for cardioembolic ischemic stroke, it could be useful in patients with non-cardioembolic ischemic stroke. Although antiplatelet therapy is the recommended treatment to prevent non-cardioembolic ischemic stroke, adding an anticoagulant might have beneficial effects through the dual-pathway inhibition strategy. Due to the potential risk of hemorrhagic transformation, there is hesitation to administer anticoagulants early to patients who have recently had an ischemic stroke, especially if they are also on antiplatelet therapy. However, clinical trials on asundexian confirmed its safety for bleeding, even when used with antiplatelets. A phase 3 trial is currently investigating the efficacy of asundexian in preventing non-cardioembolic ischemic stroke.

Milvexian, a novel factor XIa inhibitor for stroke prevention: pharmacokinetic and pharmacodynamic evaluation.

INTRODUCTION: Antiplatelets and oral anticoagulants are commonly used to treat patients with various cardiovascular and cerebrovascular diseases. However, the primary concern for clinicians remains the risk of bleeding, thus necessitating the development of new therapies. Milvexian is a new anticoagulant that inhibits factor XIa, preventing the pathological formation of thrombi without increasing bleeding risk. AREAS COVERED: This drug evaluation examines the pharmacokinetic properties of milvexian and provides information on its pharmacodynamics and clinical efficacy in treating some cerebrovascular conditions. EXPERT OPINION: Milvexian shows a good pharmacokinetic profile with low renal elimination rates, justifying its use in patients with a high degree of renal impairment, and without relevant drug-drug interactions. In patients affected by acute non-cardioembolic ischemic stroke or high-risk transient ischemic stroke, milvexian, in addition to dual antiplatelet therapy, seems to have a positive efficacy profile without any safety concerns, especially in terms of intracranial hemorrhage. Two phase 3 trials are ongoing to investigate the efficacy and safety of milvexian for preventing cardioembolic and non-cardioembolic ischemic stroke.

Ketogenic diet may improve sleep quality and daytime somnolence in patients affected by multiple sclerosis. Results of an exploratory study.

OBJECTIVE/BACKGROUND: Patients with multiple sclerosis (MS) frequently report sleep complaints. The ketogenic diet (KD) is safe and tolerable in MS patients. Our aim was: 1) to investigate the effects of KD on sleep complaints in patients affected by relapsing-remitting MS and 2) to verify if sleep changes can positively impact on psychological status and quality of life (QoL) in these patients. PATIENTS/METHODS: From January 2020 to November 2022, we consecutively enrolled 21 non-disabled or minimally disabled MS patients. We collected information regarding: 1) anthropometric measures; 2) psychological status by the Depression Anxiety Stress Scale-21; 3) QoL by the Multiple Sclerosis Quality of Life-54 (MSQOL-54); 4) subjective sleep complaints, i.e. sleep quality, by the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness (EDS), by the Epworth Sleepiness Scale (ESS). RESULTS: After 6 months of KD therapy, anthropometric measures considerably changed, psychological status significantly improved, and almost all the MSQOL-54 subscales ameliorated. Regarding sleep, we observed that the global PSQI (T0: 7.7 ± 3.1 versus T1: 4.4 ± 3.1, p = 0.002) and the ESS (T0: 7.5 ± 3.9 versus T1: 4.9 ± 3.2, p = 0.001) scores significantly decreased after KD therapy. At T1, only the global PSQI score was an independent predictor of anxiety, stress, and mental health. CONCLUSIONS: For the first time, we demonstrated that KD may improve sleep complaints in MS patients. In addition, KD seems to have a positive impact on psychological status and QoL of MS patients, mainly through improving sleep quality. Further controlled studies with larger sample sizes are needed to confirm these preliminary results.

Comparing the Impact of COVID-19 on Vaccinated and Unvaccinated Patients Affected by Myasthenia Gravis.

We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups' previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America-MGFA-Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines.