New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease: The EXCEL Trial

Background

There is limited information on the incidence and prognostic impact of new-onset atrial fibrillation (NOAF) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD).

Contemporary Antithrombotic Treatment in Patients with Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Rationale and Design of the Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry

Background

Approximately 5 to 7% of patients undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery disease require chronic oral anticoagulation (OAC) on top of aspirin and a P2Y₁₂ receptor antagonist, mainly due to non-valvular atrial fibrillation (AF). The advent of non-vitamin K antagonist oral anticoagulants (NOACs) increased treatment options, while there is cumulative evidence that dual combination of a NOAC and a P2Y₁₂ receptor antagonist attenuates risk of bleeding, compared to traditional triple therapy, consisting of a vitamin K antagonist (VKA), aspirin, and a P2Y₁₂ receptor antagonist, without significantly compromising efficacy.

Study Design

Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF, NCT 03362788) is an observational, nationwide study of non-valvular AF patients undergoing PCI, planning to enroll over 1-year period >?500 participants in 25 tertiary and non-tertiary PCI centers in Greece. Key data to be collected pre-discharge include demographics, detailed past medical history, and antithrombotic and concomitant treatment. Patients will be followed up at 1, 6, and 12 months post hospital discharge. Αt each follow-up visit, data on antithrombotic treatment, ischemic, bleeding, and adverse events will be collected. Study’s primary endpoint is clinically significant bleeding (Bleeding Academic Research Consortium, BARC ≥?2) at 12 months, between VKAs and NOACs-treated patients, analyzed using Cox proportional hazards models, by an intention-to-treat principle. An independent endpoint committee will adjudicate all clinical events.

Conclusions

This study aims at providing “real-world” information on current antithrombotic treatment patterns and clinical outcome of patients with non-valvular AF undergoing PCI.

     

Nanoformulation-by-design: an experimental and molecular dynamics study for polymer coated drug nanoparticles

The formulation of drug compounds into nanoparticles has many potential advantages in enhancing bioavailability and improving therapeutic efficacy. However, few drug molecules will assemble into stable, well-defined nanoparticulate structures. Amphiphilic polymer coatings are able to stabilise nanoparticles, imparting defined surface properties for many possible drug delivery applications. In the present article we explore, both experimentally and in silico, a potential methodology to coat drug nanoparticles with an amphiphilic co-polymer. Monomethoxy polyethylene glycol–polycaprolactone (mPEG-b-PCL) diblock copolymers with different mPEG lengths (M_w 350, 550, 750 and 2000), designed to give different levels of colloidal stability, were used to coat the surface of indomethacin nanoparticles. Polymer coating was achieved by a flow nanoprecipitation method that demonstrated excellent batch-to-batch reproducibility and resulted in nanoparticles with high drug loadings (up to 78%). At the same time, in order to understand this modified nanoprecipitation method at an atomistic level, large-scale all-atom molecular dynamics simulations were performed in parallel using the GROMOS53a6 forcefield parameters. It was observed that the mPEG-b-PCL chains act synergistically with the acetone molecules to dissolve the indomethacin nanoparticle while after the removal of the acetone molecules (mimicking the evaporation of the organic solvent) a polymer–drug nanoparticle was formed (yield 99%). This work could facilitate the development of more efficient methodologies for producing nanoparticles of hydrophobic drugs coated with amphiphilic polymers. The atomistic insight from the MD simulations in tandem with the data from the drug encapsulation experiments thus leads the way to a nanoformulation-by-design approach for therapeutic nanoparticles.

Experimental studies of drug–polymer nanoparticle formation combined with molecular dynamics simulations provide atomistic explanations for the high drug loadings obtained.