Drug Des Dev Ther
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Meta Analysis
Effect and safety of antithrombotic therapies for secondary prevention after acute coronary syndrome: a network meta-analysis.
Dual antiplatelet therapy is a standard protocol for secondary prevention after acute coronary syndrome, but despite a variety of new dual antithrombotic strategies, there is a dearth of studies evaluating the effects and safety of some popular therapies. This study used a network meta-analysis to compare the efficacy and safety of all available antithrombotic therapies. ⋯ We concluded the following from our study: 1) an aspirin + new P2Y12 inhibitor/ clopidogrel conversion treatment strategy was not inferior to aspirin + new P2Y12 inhibitor; 2) compared with aspirin + clopidogrel, the conversion strategy may further reduce the risk of myocardial infarction without increasing the risk of bleeding; and 3) compared with aspirin + clopidogrel, treatment with aspirin + new P2Y12 inhibitors may result in reduced risk of death.
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Review
Benralizumab in the treatment of severe asthma: design, development and potential place in therapy.
Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL)-5, which is mainly produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells. ⋯ Among these new treatments, anti-IL-5 monoclonal antibodies such as mepolizumab and reslizumab have been developed and clinically evaluated. Furthermore, benralizumab is currently the only available biologic drug that specifically binds to the IL-5 receptor, thus preventing the interaction with its ligand and the consequent pro-inflammatory effects. The effectiveness of benralizumab in improving severe eosinophilic asthma has been well-documented by many randomized controlled trials.
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The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors. ⋯ Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved prognosis. PD-L1 expression is a biomarker of the efficacy of durvalumab.
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Randomized Controlled Trial
Different doses of tenecteplase vs alteplase in thrombolysis therapy of acute ischemic stroke: evidence from randomized controlled trials.
Recent studies showed inconsistent results of tenecteplase vs alteplase for acute ischemic stroke (AIS) with safety and efficacy. ⋯ Tenecteplase provided better early neurological improvement than alteplase. The 0.25 mg/kg dose of tenecteplase subgroup specially showed better early neurological improvement and lower any ICH tendency than that of alteplase. In addition, in serious stroke at baseline subgroup, tenecteplase showed a lower risk of any ICH.
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Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. ⋯ Additionally, recent work linked SUR1-TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1-TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke.