Oral Antithrombotic Agents Research Articles

Impact of oral antithrombotic agents on urinary continence recovery following robot-assisted radical prostatectomy: a retrospective cohort study

BackgroundRobot-assisted radical prostatectomy (RARP) is a preferred minimally invasive surgical treatment for prostate cancer. The number of elderly patients and those with cardiovascular and/or cerebrovascular issues undergoing surgery is increasing, and many of them are taking antithrombotic (AT) agents. However, the effect of AT agents on postoperative urinary recovery has not been adequately studied. In this study, we analyzed the differences in the postoperative recovery of urinary continence and oncological outcomes in patients undergoing RARP for localized prostate cancer between AT agent adherents and non-adherents.MethodsA total of 394 patients who underwent conventional anterior RARP between February 2015 and February 2021 were categorized into two groups: those taking oral AT agents (AT group) and the control group. Urinary continence recovery, complications, and oncological outcomes were compared between the groups. A Cox proportional hazards analysis was performed to identify clinical factors that affect urinary continence recovery.ResultsThe background data and bleeding complications did not differ significantly between the groups. The recovery of continence was significantly poorer in the AT group in terms of complete pad free (HR: 0.53 [95% CI: 0.39–0.71]) and use of ≤ 1 safety pad (HR: 0.74 [95% CI: 0.59–0.94]). The rate of anastomotic leakage on cystography was significantly higher in the AT group (20.9% vs. 6.7%). A univariate analysis revealed that taking antithrombotic agents, higher prostate-specific antigen levels, and a more advanced clinical stage were associated with a poor urinary continence recovery; a multivariate analysis showed that taking AT agents was an independent factor negatively associated with urinary continence recovery. There was no significant difference between the groups in the positive surgical margin rate (19.0% vs. 23.8%) or the biochemical-recurrence-free rate.ConclusionTaking oral AT agents may be associated with poor urinary continence recovery after RARP.

Utility of prophylactic clipping after colorectal cold snare polypectomy in patients on oral antithrombotic agents

There is no consensus on the effectiveness of prophylactic clipping after colonic cold snare polypectomy (CSP). This study aimed to evaluate the utility of prophylactic clipping in preventing delayed bleeding (DB) after colorectal CSP in patients on antithrombotic agents. We retrospectively recruited consecutive patients on antithrombotic agents who underwent colorectal CSP in Chiba University Hospital. The DB rate was compared between patients with and without prophylactic clipping. The study included 133 patients (422 polyps) requiring prophylactic clipping and 85 patients (282 polyps) not requiring prophylactic clipping. The DB and hematochezia rates have no significant difference between both groups. By weighted logistic regression analysis, the odds ratio of hematochezia was 0.557 (95% confidence interval, 0.225-1.378; p = 0.205) in patients without clipping compared to those with clipping. Prophylactic clipping may not be necessary to prevent DB after colorectal CSP in patients on antithrombotic agents.

Orally administrated fucoidan and its low-molecular-weight derivatives are absorbed differentially to alleviate coagulation and thrombosis

Thrombosis is a serious threat to human health and life. Fucoidan, a sulfated polysaccharide from brown algae, could prevent coagulation and thrombus after intravenous administration. However, more efforts are still needed to develop its oral agent. In the present study, the absorption and excretion of fucoidan (90.8 kDa) and its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), were determined by HPLC-MS/MS after acid degradation and 1-phenyl-3-methyl-5-pyrazolone derivatization, and their anticoagulation and antithrombotic activities were evaluated in vivo after oral administration. Results showed that the maximum concentrations of fucoidan, Dfuc1 and Dfuc2 in rat plasma all achieved at 2 h after oral administration (150 mg/kg), and they were 41.1 ± 10.6 μg/mL, 45.3 ± 18.5 μg/mL and 59.3 ± 13.7 μg/mL, respectively. In addition, fucoidan, Dfuc1 and Dfuc2 could all prolong the activated partial thromboplastin time in vivo from 23.7 ± 2.7 s (blank control) to 25.1 ± 2.6 s, 27.1 ± 1.7 s and 29.4 ± 3.6 s, respectively. Moreover, fucoidan and its degradation products showed similar antithrombotic effect in carrageenan-induced thrombosis mice, and untargeted metabolomics analysis revealed that they all markedly regulated the carrageenan-induced metabolite disorders, especially the arachidonic acid metabolism. Thus, the degradation products of fucoidan with lower molecular weights are more attractive for the development of oral antithrombotic agents.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding – A Multicenter Nationwide Study

Introduction: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). Methods: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. Results: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. Conclusions: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Pharmacogenetic substantiation of personalized prescription of oral anticoagulants in clinical practice

Thromboembolic diseases are of great clinical concern because of their high prevalence and consequences, which are often fatal. Despite significant progress in the prevention and treatment of thrombotic events, patients remain at risk of life-threatening bleeding episodes and other side effects arising from anticoagulant therapy, so the issue of personalizing prescriptions taking into account the genetic characteristics of patients has become urgent. The purpose of the study is to substantiate the need for patient genotype analysis in order to increase the effectiveness and safety of individual pharmacotherapy. The article has a conceptual nature, therefore the following research methods were chosen: systematization and generalization; analysis and specification; abstract and logical. For the search, we used PubMed, PubMedCentral, Google Scholar, dbSNP, Elsevier, Springer from September 2000 to November 2022. The review included studies written in English and Ukrainian. There were analyzed literature data on two main subclasses of oral antithrombotic agents, including oral anticoagulants and antiplatelet agents, namely warfarin, apixaban, rivaroxaban, and clopidogrel. Prognostically significant for evaluating the effectiveness and safety of anticoagulant use, as well as the most studied in this aspect, are CYP2C9 (rs1799853, rs1057910), CYP2C19 (rs4244285, rs4986893, rs12248560), VKORC1 (rs9923231, rs7294, rs9934438), MDR1 (rs4148738, rs2032582, rs1045642), FGB (rs1800787), PAI-1 (rs1799889) genes. The results of CYP2B6, CYP3A4/5 (rs776746), CYP4F2 (rs2108622) genes analysis indicate a certain influence on the anticoagulants metabolism and require further detailed study. Factors such as age, race, sex, smoking, diet, and other medications are known to influence the effectiveness of antithrombotic therapy, but the most influential factor is genetics, which accounts a significant percentage of interindividual variability. Future research should focus on the study of known and novel genetic variants that influence drug metabolism, as well as the molecular mechanisms that contribute to changes in plasma anticoagulant levels. The article provides a brief overview of action mechanisms, pharmacogenetics, and interactions between drugs and the genes responsible for their metabolism. The results indicate the need for studies of gene variants considered in this review before starting anticoagulant therapy, and attention should also be paid to the possibility of inhibitors and inductors influence on components of the metabolic pathway of anticoagulants and gene expression products that participate in their metabolism. The totality of these measures will ensure an increase in the efficiency and safety of individual pharmacotherapy and allow optimizing the choice and dosage of anticoagulants.

Dental interventions in oral antithrombotic therapy.

Dentists commonly encounter patients taking oral antithrombotic agents who require invasive dental procedures. Although antithrombotics can cause an increase in bleeding, there is consensus that treatment regimens with antiplatelet agents, older anticoagulants (warfarin) and direct oral anticoagulants should not be altered before routine dental procedures when the risk of bleeding is low. Thromboembolic risk of their discontinuing likely outweighs potential bleeding complications associated with surgery. Therefore, the risks of stopping or reducing these medications must be weighed against the potential consequences of prolonged bleeding, which can be controlled with local measures such as mechanical pressure, suturing, haemostatic agents or antifibrinolytics. Some patients who are taking antithrombotic medications may have additional comorbid conditions or receive other therapy that can increase the risk of prolonged bleeding after dental treatment. Where a patient is believed to be at high bleeding risk, the dentist should consider a consultation with the patient's physician to discuss temporarily discontinuing the antithrombotic therapy.

Abstract 3: Cerebral Small Vessel Disease Burden For Bleeding Risk During Antithrombotic Therapy -BAT2-

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models. Results: Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P<0.001 for each). A unit increase of SVD score was associated with a higher risk of major bleeding (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.29-1.85) and intracranial hemorrhage (adjusted HR 1.61, 95% CI 1.28-2.03). With SVD score 4 compared to score 0, extracranial major bleeding (adjusted HR 3.37, 95% CI 1.12-10.15) and gastrointestinal bleeding (adjusted HR 2.54, 95% CI 1.02-6.35) were also significantly increased. A higher SVD score was associated with a mild but significant elevation of ischemic event risk (adjusted HR per unit increase 1.17, 95% CI 1.06-1.29). Conclusions: The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.

In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect-Exposure Relationship in Rat Plasma.

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent.

Efficacy and Safety of Antithrombotic Therapy With Oral Anticoagulants in Real-World Elderly Patients With Acute Coronary Syndrome and Atrial Fibrillation.

BackgroundThe efficacy and safety of antithrombotic treatment with oral anticoagulants (OACs) in elderly patients with comorbidities of acute coronary syndrome (ACS) and atrial fibrillation (AF) are unclear.MethodsA cohort of hospitalized elderly patients (≥65 years of age) diagnosed with ACS and AF and treated with oral antithrombotic agents were consecutively recruited. Follow-up was performed for at least 1 year. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. The safety outcomes of bleeding were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsA cohort of 548 eligible patients (76 ± 6.6 years) was analyzed. Compared to the patients with OAC treatment (n = 184, 33.6%), patients treated without OAC (n = 364, 66.4%) were older, had a lower prevalence of persistent AF and unstable angina (UA), and more often presented with paroxysmal AF, acute myocardial infarction (AMI), stent implantation and dual antiplatelet therapy (DAPT). Compared to the patients without OAC treatment (n = 364, 66.4%), patients treated with OAC (n = 184, 33.6%) had a lower risk of MACEs at both the 1-year (4.3 vs. 15.1%, adjusted HR: 0.34, 95% CI: 0.15–0.80, p = 0.014) and 5-year (17.5 vs. 48.4%, adjusted HR: 0.36, 95% CI: 0.19–0.67, p = 0.001) follow-up. No significant difference was observed for bleeding events of BARC ≥2 between the groups (8.0 vs. 9.0%, adjusted HR: 1.17, 95% CI: 0.58–2.34, p = 0.667). Compared with warfarin-treated patients, the non-vitamin K antagonist oral anticoagulant-treated patients had lower risks of all-cause mortality (2.1 vs. 9.5%, HR: 0.18, 95% CI: 0.03–0.98, p = 0.047) and bleeding events of BARC ≥ 3 (2.1 vs. 4.8%, HR: 0.14, 95% CI: 0.02–1.10, p = 0.062).ConclusionsAntithrombotic therapy with OACs in elderly patients with ACS and AF was associated with a lower risk of ischemic events without an increase in bleeding events. In real-world practice, the clinical awareness of anticoagulation treatments in elderly patients with ACS and AF needs to be strengthened.

Abstract 311: Different Oral Antithrombotic Therapy For The Treatment Of Ventricular Thrombus

Aim of the study: To evaluate the utilization of oral antithrombotic agents - NOACs, VKAs or antiplatelet therapy (APT) - in ventricular thrombus (VT) patients and to analyze factors for thrombus resolution and clinical outcomes. Methods: This retrospective observational study was conducted from 2010 to 2019 in National Center of Cardiovascular Diseases of China. We included patients with VT confirmed by imaging. The primary outcome was the rate of thrombus resolution. HR was calculated with or without adjustment for covariates using Cox proportional hazards regression models. Results: 298 patients were included. 45.3% (135 of 298) of them received VKAs, 20.5% (61 of 298) received NOACs, and 34.2% (102 of 298) received APT. NOACs were more likely to have the thrombus resolution within 12 weeks follow-up comparing VKAs or APT (HR 1.97, 95% CI 1.31 to 2.98, p=0.001; HR 2.65, 95% CI 1.67 to 4.20, p<0.001) with or without adjustment. In univariable analysis, patients who were diagnosed as dilated cardiomyopathy or had a history with heart failure had a greater risk to have the thrombus resolved (HR 1.89, 95% CI 1.26 to 2.85, p=0.002; HR 2.27, 95% CI 1.59 to 3.24, p<0.001). In subgroup analysis, patients with coronary artery diseases, the rate of thrombus resolution favored NOACs in comparison with VKAs or APT (HR 2.17, 95% CI 1.08 to 4.39; HR 2.16, 95% CI 1.05 to 4.43)). No significant differences were identified in bleeding rate, thromboembolism rate or all-cause death in 12 months follow-up. Conclusion: Our findings showed that patients who were diagnosed with dilated cardiomyopathy, or with a heart failure medical history had a greater thrombus resolution. Within 12 weeks follow-up, patients with NOACs had a higher resolution and a similar safety profile comparing VKAs or APT, which persisted after adjusting for other factors. Large randomized controlled trials are required urgently.

Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2.

BackgroundThe aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents.Methods and ResultsPatients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0–4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m2), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11–2.39) at category G4 (eGFR 15–<30 mL/min per 1.73 m2) and 2.05 (95% CI, 1.33–3.16) at G5 (eGFR <15 mL/min per 1.73 m2). Corresponding odds ratios relative to urinary albumin‐to‐creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12–1.49) for category A2 (ACR 30–<300 mg/g) and 1.37 (95% CI, 1.05–1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased.ConclusionsBoth reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

Determinants of Urinary Incontinence and Subtypes Among the Elderly in Nursing Homes.

Urinary incontinence (UI) is a common problem among older adults. This study investigated the prevalence of UI in nursing home residents aged ≥75 years in China and examined potential risk factors associated with UI and its subtypes. Data were collected during face-to-face interviews using a general questionnaire, the International Consultation Incontinence Questionnaire Short-Form, and the Barthel Index. A total of 551 participants aged ≥75 years residing in Changsha city were enrolled from June to December 2018. The UI prevalence rate among nursing home residents aged ≥75 years was 24.3%. The most frequent subtype was mixed (M) UI (38.1%), followed by urge (U) UI (35.1%), stress (S) UI (11.9%), and other types (14.9%). In terms of severity, 57.5% had moderate UI, while 35.1% had mild and 7.5% had severe UI. Constipation, immobility, wheelchair use, cardiovascular disease (CVD), and pelvic or spinal surgery were significant risk factors for UI. Participants with a history of surgery had higher risks of SUI (odds ratio [OR] = 4.87, 95% confidence interval [CI]: 1.55–15.30) and UUI (OR = 1.97, 95% CI: 1.05–3.71), those who were immobile or used a wheelchair had higher rates of MUI (OR = 11.07, 95% CI: 4.19–29.28; OR = 3.36, 95% CI: 1.16–9.78) and other UI types (OR = 7.89, 95% CI: 1.99–31.30; OR = 14.90, 95% CI: 4.88–45.50), those with CVD had a higher rate of UUI (OR = 2.25, 95% CI: 1.17–4.34), and those with diabetes had a higher risk of UUI (OR = 2.250, 95% CI: 1.14–4.44). Use of oral antithrombotic agents increased UUI risk (OR = 4.98, 95% CI: 2.10–11.85) whereas sedative hypnotic drug use was associated with a higher risk of MUI (OR = 3.62, 95% CI: 1.25–10.45). Each UI subtype has distinct risk factors, and elderly residents of nursing homes with a history of CVD and pelvic or spinal surgery who experience constipation should be closely monitored. Reducing time spent in bed and engaging in active rehabilitation including walking and muscle strengthening may aid in UI prevention and treatment.

Oral antithrombotic therapy for the prevention of recurrent cerebrovascular events.

Stroke is frequently a disabling and even life-threatening condition that has an ischaemic cause in most cases. Transient ischaemic attack (TIA) is a lower risk condition that still exposes to the risk of future major cardiovascular events. The causes of stroke can be classified as cardioembolic disease, large vessel disease, small vessel disease, undetermined, or others. Cardioembolic disease and atherothrombosis of large arteries are the most common underlying processes of ischaemic stroke and TIA. Therefore, antithrombotic therapy is a central strategy in the pharmacological management of these patients. However, because antithrombotic therapy provides ischaemic protection at the price of increased bleeding, defining the fine balance between efficacy and safety is a clinical challenge. Numerous trials have recently defined the current indications to the use of anticoagulant and antiplatelet therapy in patients with various subtypes of ischaemic stroke or TIA. In this review, we provide an updated appraisal of the currently available evidence on the use of various oral antithrombotic agents for prevention of recurrent events after an ischaemic stroke or TIA.

The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19.

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.

Meta-analysis on the safety and efficacy of Lumbrokinase in peripheral arterial disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Lumbrokinase, an oral anti-thrombotic and fibrinolytic agent, was not yet part of the recommendations of any recommendations but had shown in two studies that it could increase the Ankle Brachial Index (ABI). ABI was used to evaluate the drug efficacy for PAD. Purpose Peripheral Arterial Disease was one of the most neglected, under-screened, and undertreated high-risk groups among cardiovascular diseases like myocardial infarction and stroke. Few studies were done to evaluate the treatment of fibrinolytic such as Lumbrokinase for this population. Methods We appraised two randomized control trials that evaluated the safety and efficacy of Lumbrokinase compared to placebo with the standard regimen and another study of Lumbrokinase compared to placebo with standard regimen versus Lumbrokinase with Prostaglandin E1 (PGE1) among adult patients for the reduction of symptoms of PAD and increase in ABI. Both trials treatment period lasted for 2 weeks. Two independent reviewers assess the identified trials for inclusion by applying the selection criteria and quality was assessed using the JADAD scale. The data was analyzed using Meta analyst statistical software. Main results After weeks of treatment, the effect size is 0.90; this is an increase of at least +0.06 from the baseline that supports the trend in increasing the ankle-brachial index. The study did not show significant side effects by Lumbrokinase Conclusions Lumbrokinase at 460 to 490 mg three times a day for 2 weeks to 3 months has no significant relationship but has a trend in increasing the ankle-brachial index to a borderline level compared to placebo. Additional studies regarding the effect of Lumbrokinase in increasing ABI must be done with larger sample size. Further research is needed to illuminate whether a longer duration of treatment with Lumbrokinase can increase the ankle-brachial index more. Eligible Trials Table 1. Eligible trials, characteristics, and demographics.AuthorYearControlPatient enrolled (N)Patient Analysed (%)Age Mean SDMales %Diabetes %Dyslipidemia %1. NDRAHA2013PlaceboL = 10 C= 10L = 100 C = 100L = 55.8 C = 53.2L = 5 C = 5L = 35 C = 25L = 30 C = 302. LUL= 31 C = 31L = 100 C = 100L = 68 C = 68.4L = 74 C = 74NANASUM/RAW MEANSL= 41 C = 41L = 100 C = 100L = 61.9 C = 60.8L = 39.4 C = 39.4NANAL= Lumbrokinase groupC= Control groupNA = not availableAbstract Figure. Efficacy of Lumbrokinase

Mortality in relation to presence and type of oral antithrombotic agent among adult trauma patients: a single-center retrospective cohort study.

Oral anticoagulants (AC) and antiplatelet (AP) agents are increasingly prescribed to prevent and treat acute and chronic thrombotic conditions. The direct oral anticoagulants (DOAC), a newer class of AC, raise concerns in the trauma setting. Our study aims to compare the mortality rates and other outcomes among adult trauma patients based on pre-admission AC/AP status. We conducted a retrospective cohort study of a prospectively collected database of trauma patients previously on DOAC, warfarin, aspirin or clopidogrel. A matched control group of trauma patients not receiving AC/AP was used for comparison. Our primary endpoint was in-hospital mortality according to antithrombotic medication class. Secondary endpoints included length of stay (LOS), intensive care unit (ICU) admission, need for blood transfusion, and discharge to a dependent setting. Univariate and multivariate analyses were conducted. There were 996 exposed patients and 234 controls, with no major clinically significant difference among study groups in terms of gender, injury site, injury severity, mechanism, and comorbidities. The mortality rates were 2.14% (control, 5/234), 2.88% (DOAC, 3/104), 3.34% (aspirin, 17/509), 7.63% (warfarin, 18/236), 9% (clopidogrel, 8/89), and 13.79% (aspirin + clopidogrel, 8/58) (p < 0.001). In multivariate analyses, there was no difference regarding mortality between DOAC and reference groups. Blood transfusion was more likely in patients receiving warfarin or AP than those prescribed DOAC. There was no evidence of increased mortality or blood transfusion requirement among trauma patients on DOAC, including head trauma patients. Further studies on head trauma and specific subgroups of DOAC are recommended.

Wpływ migotania przedsionków na przebieg kliniczny i leczenie pacjentów z niewydolnością serca — dane z wieloośrodkowego rejestru

Introduction. When heart failure (HF) and atrial fibrillation (AF) afflict the same patient simultaneously, it becomes a challenge for cardiologists. This is not only due to the need to intensify preventive measures to reduce the prevalence of common aetiological factors, but also due to growing healthcare costs, particularly care costs for elderly patients at high risk of accumulated complications of both diseases. Our study was aimed at evaluating the concomitant incidence of AF on the natural history and treatment of Polish HF patients on the basis of data obtained in a multicentre registry study. Material and methods. In this study, the population subjected to retrospective analysis consisted of Polish patients included in the long-term ESC-HF registry study (N = 1,126). A comparative analysis of the study group (AF+) and the control group (AF−) was carried out. Results . No differences were observed in the rates of in-hospital deaths between the (AF+) and the (AF−) group: 2.9% versus 2.8%, [p = not significant (NS)]. The average duration of hospitalisation in the AF+ group was 9.8 ± 14.7 days compared to 8.8 ± 10.9 days in the AF− group (p = NS). In the AF+ group, compared to the AF− group, significantly higher frequencies were recorded for the following parameters: exacerbation of chronic HF as the cause of hospitalisation, intravenous diuretics usage during hospitalisation, electrical cardioversion, as well as in-hospital use of mineralocorticoid receptor antagonists, diuretics, digoxin, oral antithrombotic agents and amiodarone. Conclusions. In the population of HF patients requiring hospitalisation, the AF+ subgroup is characterised by poorer clinical condition (biventricular cardiac decompensation, lower systolic blood pressure, higher heart rate on admission, and more frequent use of intravenous diuretics). The concomitance of AF significantly impacts the natural history and treatment of HF patients.

Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding: The MARK Study.

BackgroundOptimal management of antithrombotic agents during surgery has yet to be established. We performed a prospective multicenter observational study to determine the current status of the management of antithrombotic agents during surgery or other medical procedures with bleeding (MARK [Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding] study) in Japan.Methods and ResultsThe participants were 9700 patients who received oral antithrombotic agents and underwent scheduled medical procedures with bleeding at 59 National Hospital Organization institutions in Japan. Primary outcomes were thromboembolic events, bleeding events, and death within 2 weeks before and 4 weeks after the procedures. We investigated the relationships between each outcome and patient demographics, comorbidities, type of procedure, and management of antithrombotic therapy. With respect to the periprocedural management of antithrombotic agents, 3551 patients continued oral antithrombotic agents (36.6%, continuation group) and 6149 patients discontinued them (63.4%, discontinuation group). The incidence of any thromboembolic event (1.7% versus 0.6%, P<0.001), major bleeding (7.6% versus 0.4%, P<0.001), and death (0.8% versus 0.4%, P<0.001) was all greater in the discontinuation group than the continuation group. In multivariate analysis, even after adjusting for confounding factors, discontinuation of anticoagulant agents was significantly associated with higher risk for both thromboembolic events (odds ratio: 4.55; 95% CI, 1.67–12.4; P=0.003) and major bleeding (odds ratio: 11.1; 95% CI, 2.03–60.3; P=0.006) in procedures with low bleeding risk. In contrast, heparin bridging therapy was significantly associated with higher risk for both thromboembolic events (odds ratio: 2.03; 95% CI, 1.28–3.22; P=0.003) and major bleeding (odds ratio: 1.36; 95% CI, 1.10–1.68; P=0.005) in procedures with high bleeding risk.ConclusionsDiscontinuation of oral antithrombotic agents and addition of low‐dose heparin bridging therapy appear to be significantly associated with adverse events in the periprocedural period.

Development and activity evaluation of Arg-Gly-Asp-containing antithrombotic conjugate

Poly-α,β-D,L-aspartic acid (PD) is highly susceptible to the degradation of lysosomal enzyme and produce monomeric aspartic acid as the product. Exogenous RGD-containing sequences could inhibit platelet aggregation and formation of thrombosis by competitively binding to activated platelet membrane GPIIb/IIIa receptors. Poly-α,β-D,L-aspartyl-Arg-Gly-Asp-Ser (PD-RGDS) was synthesized by conjugating anti-thrombotic RGDS to the highly biodegradable poly-α,β-D,L-aspartic acid molecules (PD) and its structure was confirmed. PD-RGDS existed as the nanoparticles of 60–108 nm at 10−6 M by TEM and SEM. In vitro anti-platelet aggregation assay showed that PD-RGDS could preferentially inhibit platelet aggregation induced by PAF (IC50 33.5 nM). In vivo antithrombotic activity of PD-RGDS was evaluated with a rat model of carotid artery and venous bypass cannulation. PD-RGDS had increased antithrombotic activity (1 nmol/kg by ig.) compared with RGDS(5 μmol/kg). Furthermore, to measure blood concentration of PD-RGDS in rats, FITC-PD-RGDS was prepared and had an elimination half-life of 240.3 ± 49.6 min by intragastric administration of 50 mg/kg. Therefore PD-RGDS could be built as a novel oral antithrombotic agent.

Contemporary Use of Oral Antithrombotic Agents: Focus on Dual and Triple Therapeutic Approaches.

Atherosclerotic cardiovascular disease (ASCVD) represents a long-standing health care burden in most industrialized countries. Management of ASCVD is multifaceted, and utilization of antithrombotic agents is a key component of care to reduce vascular events. Minimizing thrombotic risk can be accomplished via antiplatelet or anticoagulant drugs; however, combination therapy is warranted for some indications. Although reducing thrombotic complications is important, it is equally vital to consider the safety of combination regimens. Thus clinicians must effectively balance both individualized thrombotic and bleeding risks when using this strategy. Scenarios occur in practice when determining the role for combination therapy is not clear, especially for patients with ASCVD who require both dual antiplatelet therapy plus anticoagulation. The aim of this review is to discuss the role of dual or triple antithrombotic therapies across the spectrum of thrombotic disease states. In addition to critiquing relevant research studies and evaluating key recommendations from nationally published guidelines and consensus statements involving the use of these agents, we offer practical considerations that can be utilized when managing patients with ASCVD.