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1.
A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve.
Thomson, BKA, Pilkey, NG, Monteith, B, Holden, RM
American journal of nephrology. 2021;(10-11):861-870
Abstract
INTRODUCTION Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy. METHODS A scoping review was completed, searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Conference abstracts from inception to March 30, 2021. The study population was patients with ESRD who were on VKA therapy and developed a contraindication to VKA therapy use. All data regarding studies, patient characteristics, anticoagulation strategy, and clinical outcomes were summarized. RESULTS Twenty-three articles met inclusion criteria. These articles included 57 patients. Contraindications to VKA therapy included calcific uremic arteriolopathy (CUA) (n = 55) and warfarin-induced skin necrosis (n = 2). All studies were either case reports or case series. There were 10 anticoagulation strategies identified. Continuation of VKA therapy was associated with increased death and decreased rates of CUA resolution (80.0% and 10.0%, respectively), compared to apixaban (24.0% and 70.8%), subcutaneous (SC) low-molecular-weight heparin (LMWH) (14.3%, 85.7%), and SC unfractionated heparin (0.0%, 100.0%). While only 5 patient cases were reported with mechanical heart valves, SC LMWH use has been reported in this context with good outcomes. CONCLUSIONS In patients with ESRD who develop a contraindication to VKA therapy, several alternative anticoagulation strategies have been reported with superior outcomes to VKA continuation. While outcomes appear superior to continuation of VKA therapy, more data are required before definitive recommendations can be made for the patient with ESRD and a mechanical heart valve.
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2.
Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective.
Hamidi, SH, Kadamboor Veethil, S, Hamidi, SH
Pharmacological reports : PR. 2021;(3):712-727
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pulmonary injury or multiple-organ injury by various pathological pathways. Transforming growth factor-beta (TGF-β) is a key factor that is released during SARS-CoV-2 infection. TGF-β, by internalization of the epithelial sodium channel (ENaC), suppresses the anti-oxidant system, downregulates the cystic fibrosis transmembrane conductance regulator (CFTR), and activates the plasminogen activator inhibitor 1 (PAI-1) and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kB). These changes cause inflammation and lung injury along with coagulopathy. Moreover, reactive oxygen species play a significant role in lung injury, which levels up during SARS-CoV-2 infection. DRUG SUGGESTION Pirfenidone is an anti-fibrotic drug with an anti-oxidant activity that can prevent lung injury during SARS-CoV-2 infection by blocking the maturation process of transforming growth factor-beta (TGF-β) and enhancing the protective role of peroxisome proliferator-activated receptors (PPARs). Pirfenidone is a safe drug for patients with hypertension or diabetes and its side effect tolerated well. CONCLUSION The drug as a theoretical perspective may be an effective and safe choice for suppressing the inflammatory response during COVID-19. The recommendation would be a combination of pirfenidone and N-acetylcysteine to achieve maximum benefit during SARS-CoV-2 treatment.
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3.
Direct Oral Anticoagulants in End-Stage Renal Disease.
Klil-Drori, AJ, Tagalakis, V
Seminars in thrombosis and hemostasis. 2018;(4):353-363
Abstract
Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical trials with oral anticoagulants. While such patients are at an increased risk of venous and arterial thromboembolism, their risk of bleeding is also elevated. It is thus of little surprise that stroke prevention with vitamin K antagonists (VKAs) in ESRD patients with atrial fibrillation is controversial, with observational evidence ranging from beneficial to harmful. This uncertainty extends to the less studied use of VKAs for venous thromboembolism in ESRD. The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive labeling in the United States for atrial fibrillation in patients with ESRD; this expanded labeling has not yet occurred either in Europe or for venous thromboembolism. This review summarizes the current evidence for the pharmacology of DOACs in ESRD as well as their utilization and safety in patients with ESRD and atrial fibrillation.
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4.
Clinical Pharmacokinetics and Drug Interactions of Doravirine.
Wilby, KJ, Eissa, NA
European journal of drug metabolism and pharmacokinetics. 2018;(6):637-644
Abstract
Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor that has demonstrated a good efficacy and safety profile in clinical trials. It has a therapeutic profile that makes it an attractive option for treatment of HIV-1 infection. As such, there has been an increase in the published literature regarding the pharmacokinetics of doravirine and potential for drug-drug interactions. This review aimed to identify pharmacokinetic literature pertaining to doravirine, used findings from the literature to summarize its pharmacokinetic profile, and finally evaluated literature describing actual and potential drug interactions. Review findings show doravirine is well-absorbed, exhibits moderate protein binding activity, and is extensively metabolized by cytochrome P450 enzymes (specifically CYP3A). It has an elimination half-life of 12-21 h. Gender, age, moderate hepatic impairment, and co-administration with food did not greatly alter doravirine's pharmacokinetic profile. Drug interaction studies have shown doravirine does not affect the pharmacokinetics of dolutegravir or atorvastatin but may have its pharmacokinetics altered by rifampicin (rifampin) and other rifamycins (CYP3A inducers) and ritonavir (CYP3A inhibitor). No clinically significant interactions were noted between doravirine and an antacid (aluminum-magnesium), pantoprazole, ledipasvir/sofosbuvir, or elbasvir/grazoprevir. Further study is needed to better understand doravirine's efficacy and safety profile when co-administered with other agents known to be CYP inducers or inhibitors.
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5.
Self-Assembly of Bolaamphiphilic Molecules.
Dhasaiyan, P, Prasad, BLV
Chemical record (New York, N.Y.). 2017;(6):597-610
Abstract
The current buzzword in science and technology is self-assembly and molecular self-assembly is one of the most prominent fields as far as research in chemical and biological sciences is concerned. Generally, self-assembly of molecules occurs through weak non-covalent interactions like hydrogen bonding, π-π stacking, hydrophobic effects, etc. Inspired by many natural systems consisting of self-assembled structures, scientists have been trying to understand their formation and mimic such processes in the laboratory to create functional "smart" materials, which respond to temperature, light, pH, electromagnetic field, mechanical stress, and/or chemical stimuli. These responses are usually manifested as remarkable changes from the molecular (e. g., conformational state, hierarchical order) to the macroscopic level (e. g., shape, surface properties). Many molecules such as peptides, viruses, and surfactants are known to self-assemble into different structures. Among them, glycolipids are the new entries in the area of molecules that are being investigated for their self-assembly characteristics. Among the different classes of glycolipids like rhamnolipids and trehalose lipids, owing to their biological preparations and their structural novelty, sophorolipids (SLs) are evoking greater interest among researchers. Sophorolipids are a class of asymmetric bolas bearing COOH groups at one end and sophorose (dimeric glucose linked by an unusual β(1→2) linkage). The extreme membrane stability of Archaea, attributed to the membrane-spanning bolas (tetraether glycolipids), has inspired chemists to unravel the molecular designs that underpin the self-assembly of bolaamphiphilic molecules. Apart from these self-assembled structures, bolaamphiphiles find applications in many fields such as drug delivery, membrane mimicking, siRNA therapies, etc. The first part of this Personal Account presents some possible self-assembled structures of bolaamphiphiles and their mechanism of formation. The later part covers our work on one of the typical bolaamphiphiles known as sophorolipids.
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6.
Meta-analysis of efficacy and safety of apixaban and uninterrupted apixaban therapy compared to vitamin K antagonists in patients undergoing catheter ablation for atrial fibrillation.
Ukaigwe, A, Shrestha, P, Karmacharya, P, Hussain, SK, Samii, S, Gonzalez, MD, Wolbrette, D, Naccarrelli, GV
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2017;(2):223-233
Abstract
BACKGROUND Apixaban is a Factor Xa inhibitor increasingly being used for stroke prevention in atrial fibrillation (AF). Although several studies have been done, the efficacy and safety of apixaban during the peri-procedural period of AF ablation remains unclear. We sought to systematically review pooled data from these various studies to evaluate thromboembolic and bleeding risks in patients undergoing catheter ablation for AF who are treated with apixaban (interrupted and uninterrupted). METHODS Studies comparing anticoagulation with apixaban or vitamin K antagonists (VKA) in patients undergoing ablation for AF were identified via an electronic search of MEDLINE, EMBASE, clinical trials.gov, and Cochrane Library from inception to January 2016. Study-specific risk ratios were calculated and combined with a fixed-effects model meta-analysis. RESULTS In the analysis of 2100 pooled patients, thromboembolic complications (TE) occurred in 14/778 (1.80 %) patients in the apixaban group (AG) compared to 20/1322 patients in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2 = 0 %). Major bleeding occurred in 9/778 (1.2 %) of the AG compared to 20/1322 (1.51 %) in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2 = 0 %). In uninterrupted apixaban group (uAG), TE occurred in 4/585 (0.68 %) patients in the uAG compared to 6/910 (0.66 %) in VKA group (RR 0.86, 95 % CI 0.25-2.95, p = 0.81, I 2 = 0 %). Major bleeding occurred in 5/585 (0.85 %) in uAG compared to 7/910 (0.77 %) in the VKA group (RR 1.20, 95 % CI 0.37-3.88, p = 0.76, I 2 = 0 %). CONCLUSION Our study demonstrates patients treated with apixaban and VKA during the peri-procedural period for AF ablation have similar rates of TE and bleeding complications. Interrupted and uninterrupted apixaban strategies were associated with similar outcomes.
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7.
New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.
Pelliccia, F, Rollini, F, Marazzi, G, Greco, C, Gaudio, C, Angiolillo, DJ, Rosano, G
International journal of cardiology. 2016;:154-158
Abstract
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.
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8.
Preventing Thrombosis to Improve Outcomes in Heart Failure Patients.
Shantsila, E, Lip, GY
Progress in cardiovascular diseases. 2016;(4):386-92
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Abstract
Heart failure (HF) is associated with an increased risk of thrombotic events, particularly if this condition is accompanied by atrial fibrillation (AF). Many HF patients have background coronary artery disease (CAD) making them prone to coronary thrombosis resulting in myocardial infarction or sudden death. Oral anticoagulation is essential in the vast majority of HF patients with AF with non-vitamin K based anticoagulants being a suitable alternative to warfarin. In contrast, aspirin alone does not provide adequate stroke prevention in such patients. In HF without AF, oral anticoagulation should not be routinely used, and antiplatelet agents should be prescribed in patients with background CAD. This review provides an overview of prothrombotic factors and antithrombotic management of patients with HF.
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Meta-Analysis of Efficacy and Safety of Apixaban in Patients Undergoing Catheter Ablation for Atrial Fibrillation.
Lu, D, Liu, Q, Wang, K, Zhang, QI, Shan, QJ
Pacing and clinical electrophysiology : PACE. 2016;(1):54-9
Abstract
BACKGROUND The efficacy and safety of apixaban in patients undergoing catheter ablation (CA) for atrial fibrillation (AF) are little investigated. METHODS The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE were searched up to September 2015. Four literatures comparing apixaban with vitamin K antagonists (VKAs) were included. Data were pooled in Review Manager Software, using Mantel-Haenszel methods with a fixed-effects model. The funnel plots and Egger's test were used to examine publication bias. Heterogeneity was assessed using the I(2) test. Risk ratios (RR) and 95% confidence intervals (CI) of each study were calculated and pooled. RESULTS No significant differences were observed in rates of total bleeding (RR = 0.91, 95% CI [0.57, 1.46], I(2) = 0.0%), thromboembolic complications (RR = 0.75, 95% CI [0.03, 18.22], I(2) = 0.0%), or total events (RR = 0.90, 95% CI [0.56, 1.44], I(2) = 0.0%) between apixaban and VKAs group. The frequency of major bleeding was similar between apixaban and VKAs group (RR = 1.34, 95% CI [0.34, 5.30], I(2) = 0.0%). CONCLUSION Apixaban was as effective and safe as VKAs in the periprocedural period of CA.
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10.
New treatments in idiopathic pulmonary fibrosis.
Strâmbu, I
Pneumologia (Bucharest, Romania). 2016;(3):127-32
Abstract
Idiopathic pulmonary fibrosis is a chronic fibrotic pulmonary disease of unknown origin, with an unfavourable prognosis, leading to death by respiratory failure in most patients within 3-5 years ofdiagnosis. Several drugs were studied for the treatment of this disease, and most of them were not able to stop the relentless evolution of the disease (warfarin, corticosteroids in combination with azathioprine, N-acetylcysteine, ambrisentan, bosentan, sildenafil, antiacids). Two novel drugs, pirfenidone and nintedanib, proved effective in reducing lung function decline, improving the patient’s quality of life, and increasing the patient’s probability of survival. These drugs were approved by international health authorities for use in the treatment of IPF patients. The paper refers also to the status of IPF patients in Romania, where epidemiological data are not known, and where the disease is most likely severely underdiagnosed. Patients are typically diagnosed late, and are therefore in advanced stages of the disease. A proactive attitude, in favour of identification and early diagnosis of IPF patients is highly needed in order to offer to these patients the opportunity of treatment, improved survival, and a better quality of life.