Background: The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear.
Methods: The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk.
Results: Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction values: 0.90 and 0.37, respectively). Importantly, a similar risk of the efficacy end point was observed between dabigatran dual and warfarin triple therapy, regardless of the presence of clinical or procedural complexity factors (interaction values: 0.67 and 0.54, dabigatran 110 and 150 mg dual therapy, respectively). Similar benefit was seen for each dose of dabigatran dual therapy for bleeding events regardless of dual antiplatelet therapy score (interaction values: 0.53 and 0.54, respectively), with similar risk of thromboembolic events (interaction values: 0.20 and 0.08, respectively).
Conclusions: In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT02164864.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008349 | DOI Listing |
Prog Biophys Mol Biol
December 2024
Molecular Biotechnology, Turkish-German University, Sahinkaya Caddesi No. 106, Beykoz, Istanbul 34820 Turkey. Electronic address:
The intersection of electromagnetic radiation and neuronal communication, focusing on the potential role of biophoton emission in brain function and neurodegenerative diseases is an emerging research area. Traditionally, it is believed that neurons encode and communicate information via electrochemical impulses, generating electromagnetic fields detectable by EEG and MEG. Recent discoveries indicate that neurons may also emit biophotons, suggesting an additional communication channel alongside the regular synaptic interactions.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Pinotbio, Inc Suwon, Gyeonggi-do 16506, South Korea.
FL118, a camptothecin derivative with dual mechanisms of action through topoisomerase I inhibition and proteasome-mediated degradation of anti-apoptotic proteins exhibits potent anti-tumor activity while remaining resistant to drug efflux transporters. This work describes the targeted delivery of FL118 to tumors via antibody-drug conjugates (ADCs) using the pH-sensitive CL2A linker. ADCs targeting Trop2, HER2, and EGFR exhibited potent in vitro cytotoxicity, with IC values as low as 0.
View Article and Find Full Text PDFACS Nano
December 2024
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P. R. China.
Chemotherapy is the primary treatment option for pancreatic cancer, although nanocarrier-based drug delivery systems often struggle with multiple physiological barriers, limiting their therapeutic efficacy. Here, we developed a pH/reactive oxygen species (ROS) dual-sensitive self-adaptive nanocarrier (DAT) encapsulating camptothecin (CPT), an analog of the pancreatic chemotherapeutic drug irinotecan (CPT-11), to enhance chemotherapy outcomes in orthotopic pancreatic cancer by addressing multiple physiological barriers. The nanocarrier features a peripherally positively charged arginine (Arg) residue on DAT and is masked with an acid-labile 2,3-dimethylmaleic anhydride (DA) to improve circulation time.
View Article and Find Full Text PDFAdv Ther
December 2024
GSK, US Value Evidence and Outcomes, Collegeville, PA, 19426-0989, USA.
Introduction: Chronic obstructive pulmonary disease (COPD) is associated with exacerbations which can reduce quality of life and increase mortality. Single-inhaler triple therapy (SITT) is recommended for maintenance treatment of COPD among patients experiencing exacerbations despite dual-therapy use. This real-world comparative effectiveness study compared the impact of SITTs, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM), on COPD exacerbations and mortality.
View Article and Find Full Text PDFIran J Immunol
December 2024
Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Background: Developing effective targeted treatment approaches to overcome drug resistance remains a crucial goal in cancer research. Immunotoxins have dual functionality in cancer detection and targeted therapy.
Objective: This study aimed to engineer a recombinant chimeric fusion protein by combining a nanobody-targeting domain with an exotoxin effector domain.
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