Warfarin Anticoagulation Research Articles

Commonly Prescribed Anticoagulants Exert Anticancer Effects in Oral Squamous Cell Carcinoma Cells In Vitro.

Simple SummaryOral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with 840,000 new cases and 420,000 deaths in 2020. Anticoagulants are widely prescribed medications routinely administered to help prevent blood clots. Despite the great relevance of these two topics, there is complete lack of knowledge regarding the potential effects that these drugs could exert on oral cancer patients. In this in vitro study, we comprehensively investigated the effect of anticoagulants on OSCC activity. This includes the effect of these drugs on cancer cell ability to survive, migrate to colonise distant sites, and resist treatment with conventional chemotherapy. We have demonstrated for the first time that various anticoagulants have anticancer effects on OSCC. Moreover, some of the anticoagulants tested were able to reduce the migratory ability of cancer cells. Finally, the great majority of anticoagulants studied reduced the effectiveness of the tested chemotherapeutic agent, allowing an increase in cancer cell proliferation. Our results highlight the need for urgent further research in the field, to improve the anticoagulant strategies in patients with oral cancer, and in turn their prognosis.Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. With anticoagulant usage on the rise, it is important to elucidate their potential effects on tumour biology and interactions with chemotherapeutics. The aim of the present study was to investigate the effects of anticoagulants on OSCC cell lines and their interactions with the drug 5-fluorouracil (5-FU). Cell proliferation was assessed using an MTS in vitro assay in two human OSCC cell lines (H357/H400) and in normal oral keratinocytes (OKF6) treated with the 5-FU (0.2/1/5/10 μg/mL), conventional anticoagulants warfarin (1/5/10/20 μM) and heparin (5/20/80 U), as well as four new oral anticoagulants, dabigatran (5/10/20 μM), rivaroxaban (5/10/20 μM), apixaban (0.1/1/5 μg/mL), and edoxaban (5/10/20 μM). Cell migration was assessed at 3 h intervals up to18 h using a wound healing assay. Our results clearly demonstrate, for the first time, that commonly prescribed anticoagulants exert in vitro antiproliferative effects on OSCC cells. Furthermore, treatment with some anticoagulants reduced the migration of OSCC cell lines. Nevertheless, most of the anticoagulants tested reduced the effectiveness of the chemotherapeutic agent tested, 5-FU, highlighting potential flaws in the current pharmacological management of these patients. Our findings showed the need for the immediate translation of this research to preclinical animal models.

Ilioinguinal and Iliohypogastric Nerve Blockade as an Adjunct for Inguinal Hernioplasty in a Patient with Aortic Valve Replacement: Case Report

Choosing appropriate anesthetic modality in patients with compromised cardiac function with the administration of peripheral nerve block ensures hemodynamic stability. We present the case of a 63y, male patient with an operative history of aortic valvuloplasty, on anticoagulant warfarin. Patient was given general anesthesia and supraglottic airway device, LMA was inserted to prevent intubation response. This was supplemented with USG guided ilioinguinal and iliohypogastric nerve blocks with inj ropivacaine 0.325%, 15ml and inj dexamethasone 2mg as adjuvant. Addition of peripheral nerve blockade to general anesthesia provided perioperative analgesia, so quick emergence and recovery was possible.

Effectiveness of prophylactic clipping in preventing postpolypectomy bleeding in oral anticoagulant users: a propensity-score analysis

Evidence of prophylactic clipping is inconsistent except for proximal and large colonic lesions in the general population. Although warfarin and direct oral anticoagulants (DOACs) are significant risk factors of postpolypectomy bleeding (PPB), dedicated studies to examine the benefit of prophylactic clipping in these high-risk patients remain limited. We performed a propensity score-weighted retrospective cohort study from 2012 to 2020. Patients who received an oral anticoagulant and underwent colonoscopic polypectomy were included. Data were collected on baseline demographics, medications (anticoagulant, antiplatelet, and heparin bridging), and endoscopies (polyp number, location, size, morphology, histopathology, resection method and prophylactic clipping). Propensity-score models with inverse probability of treatment weighting were developed between prophylactic clipping and no clipping groups. Unbalanced variables were included in a doubly robust model with multivariate analysis. The primary outcome was clinically significant delayed PPB, defined as a composite endpoint of hemoglobin drop≥2 g/dL, blood transfusion, or repeat colonoscopy for hemostasis within 30 days. Five hundred forty-seven patients with 1485 polyps were included. Prophylactic clipping was not associated with a reduced risk of PPB (odds ratio [OR], 1.19; 95% confidence interval [CI], .73-1.95; P= .497). The hot resection method was associated with a significantly higher risk of PPB (OR, 9.76; 95% CI, 3.94-32.60; P< .001) compared with cold biopsy or snare polypectomy. In a subgroup analysis, prophylactic clipping was associated with a lower PPB risk in patients on DOACs (OR, .36; 95% CI, .16-.82; P= .015). Prophylactic clipping was not associated with an overall reduced risk of PPB in patients on oral anticoagulants. The use of cold snare polypectomy should be maximized in anticoagulated patients.

Oral Anticoagulant Use for Patients with Atrial Fibrillation with Concomitant Anemia and/or Thrombocytopenia

ObjectiveHemoglobin levels and platelet counts have been associated with adverse clinical outcomes in patients with cardiovascular conditions. We aimed to assess the impact of oral anticoagulant use for patients with atrial fibrillation and concomitant anemia or thrombocytopenia. MethodsWe used medical data from a multicenter health care system in Taiwan including 37,074 patients with atrial fibrillation. Patients were categorized into 3 groups based on hemoglobin and platelet levels: Group 1 (hemoglobin >10g/dL and platelet>100 K/µL; n = 29,147), Group 2 (hemoglobin<10 g/dL or platelet<100 K/µL; n = 7078), and Group 3 (hemoglobin <10 g/dL and platelet <100 K/µL; n = 849). Patients in each category were further stratified as 3 groups according to their stroke prevention strategies: no oral anticoagulant use (non-OAC), warfarin, or nonvitamin K antagonist oral anticoagulants (NOACs). ResultsA higher hemoglobin or platelet level was associated with a higher risk of ischemic stroke/systemic embolism but lower risks of intracranial hemorrhage and major bleeding. The composite risks of ischemic stroke/systemic embolism, intracranial hemorrhage and major bleeding were higher in Group 3 or Group 2, compared with Group 1 (6.79% a year vs 6.41% year vs 4.13% year). Compared to non-OACs, warfarin was not associated with a lower composite risk in the 3 groups. NOACs were associated with a lower composite risk in Group 1 (adjusted hazard ratio:0.68, [95% confidence interval:0.60-0.76]) and Group 2 (adjusted hazard ratio:0.73, [95% confidence interval:0.53-0.99]) but was nonsignificant in Group 3. ConclusionsPatients with atrial fibrillation with anemia or thrombocytopenia were a high-risk population. Compared with no OAC use, NOACs were associated with better clinical outcomes for patients with atrial fibrillation and advanced anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet <100 K/µL) but not for those with both conditions.

Outcomes in Patients with a Centrifugal Flow with Full Magnetic Levitation Left Ventricular Assist Device (CF-FML LVAD) Who Did Not Receive Bridging with a Continuous Heparin Infusion (CHI) After Implantation

PurposeCompare outcomes in CF-FML LVAD patients who received a CHI after implantation until they reached a therapeutic INR on warfarin to patients who were started on warfarin only and did not receive a CHI.MethodsA retrospective analysis using chart review and the institutional LVAD database was completed on 27 patients.Results5 of the 27 patients did not receive a CHI after implantation of CF-FML LVAD (due to a medication shortage), they were started on warfarin post-operative day 1 or 2 (POD1 or POD2) for an INR goal of 2-3. CHI was initiated on the remaining patients (DOS-POD8) and PTT reached therapeutic range POD2 (DOS-POD9). 2 patients did not reach therapeutic PTT before their INR was therapeutic. The CHI patients were started on warfarin POD4 (DOS-POD14). INR was therapeutic for patients without CHI POD6 (POD5-POD11). INR was therapeutic for patients with CHI POD10 (POD2-POD31). The no CHI patients reached therapeutic INR faster and were discharged from index hospitalization sooner. The no CHI patients had similar or less adverse events (AEs) then the CHI patients (Image 1).ConclusionIn a small cohort of patients, initiation of warfarin anticoagulation without CHI was not associated with thromboembolic complications. Further work to identify populations of LVAD supported patients who need less anticoagulation post-operatively is warranted before considering practice changes. Compare outcomes in CF-FML LVAD patients who received a CHI after implantation until they reached a therapeutic INR on warfarin to patients who were started on warfarin only and did not receive a CHI. A retrospective analysis using chart review and the institutional LVAD database was completed on 27 patients. 5 of the 27 patients did not receive a CHI after implantation of CF-FML LVAD (due to a medication shortage), they were started on warfarin post-operative day 1 or 2 (POD1 or POD2) for an INR goal of 2-3. CHI was initiated on the remaining patients (DOS-POD8) and PTT reached therapeutic range POD2 (DOS-POD9). 2 patients did not reach therapeutic PTT before their INR was therapeutic. The CHI patients were started on warfarin POD4 (DOS-POD14). INR was therapeutic for patients without CHI POD6 (POD5-POD11). INR was therapeutic for patients with CHI POD10 (POD2-POD31). The no CHI patients reached therapeutic INR faster and were discharged from index hospitalization sooner. The no CHI patients had similar or less adverse events (AEs) then the CHI patients (Image 1). In a small cohort of patients, initiation of warfarin anticoagulation without CHI was not associated with thromboembolic complications. Further work to identify populations of LVAD supported patients who need less anticoagulation post-operatively is warranted before considering practice changes.

Investigating the experience of parents who have given their infants enoxaparin at home

IntroductionEnoxaparin is a common anticoagulant used in infants for the prevention and treatment of thrombosis. When administered with the purpose of treating a thrombosis, the duration of treatment is six to twelve weeks. Enoxaparin must be injected subcutaneously, either by direct injection or via an indwelling subcutaneous catheter (Insuflon™). Once discharged from hospital, parents/caregivers of infants and small children take responsibility for the safe preparation and administration of the enoxaparin which can be difficult and confronting. Whilst there is documented evidence about the benefits of targeted education for warfarin anticoagulation and the impact this has on the quality of life for children and their families, this has not been investigated in a cohort of children requiring enoxaparin anticoagulation. We therefore explored the educational needs of parents whose infants require enoxaparin anticoagulation after discharge to inform future practice to optimise delivery of care as well as improve patient safety and outcomes. Materials & methodsA qualitative, descriptive methodology was employed using focus groups to generate rich descriptive data. ResultsOur results show that parents were traumatised by the process of managing their infant's enoxaparin, and that they may benefit from a formal, more structured educational program to facilitate this treatment in the future. ConclusionIt is recognised that enoxaparin therapy in infants may be a traumatic experience for parents and caregivers. The availability of an educational resource for families to refer to once discharged, as well as ongoing communication with the treating medical team is vital.

Perioperative Antithrombotic Management During Gastroenterological Surgery in Patients With Thromboembolic Risks: Current Status and Future Prospects.

Antiplatelet medicines and anticoagulants are two types of antithrombotic pharmaceuticals, with anticoagulants including warfarin and direct oral anticoagulants (DOACs). During the perioperative phase, patients receiving antithrombotic therapy must balance two risks: bleeding and thromboembolism. To date, there are no defined recommendations for antithrombotic drug management in gastroenterological (GE) surgery, and the management strategy varies greatly between hospitals. The perioperative treatment of antithrombotic medications should be centralized according to the mechanism of each drug, and a suitable management strategy should be established. The proposed perioperative management for patients undergoing antithrombotic therapy is as follows: (1) in the case of antiplatelet medication, aspirin monotherapy is continued; (2) for patients on warfarin, it is substituted by DOAC bridging (preferred) or heparin bridging; and (3) in the case of DOACs, the short-term withdrawal of DOACs (typically 1-2 days) without heparin bridging is indicated. In the current review, the current state and future prospects of perioperative antithrombotic medication treatment during gastroenterological surgery are discussed.

Platelet membrane-cloaked selenium/ginsenoside Rb1 nanosystem as biomimetic reactor for atherosclerosis therapy

Cardiovascular disease remains the dominant contributor to human mortality, and the main etiology of which is atherosclerosis (AS). Enhancing the targeted ability of nanosystem and improving plaque stability are critical challenges for the current management of AS. Herein, we leverage the marked role of platelets in AS to construct a biomimetic nanodrug delivery system (PM@Se/Rb1 NPs), which prepared by cloaking platelet membrane (PM) around Selenium (Se) and ginsenoside Rb1 nanoparticles (Se/Rb1 NPs) core. The core endows the delivery system antioxidant, lipid metabolism and anti-inflammatory effects for AS effective treatment. Moreover, PM-coated nanoparticles reserve platelets’ inherent biological elements to deliver drugs to plaques. We further explored the potential effect of PM@Se/Rb1 NPs’ combination with the clinical anticoagulant drug warfarin (War) to treat AS and elucidated the possible drug interaction mechanism. As a result, the PM@Se/Rb1 NPs are not only capable of improving inflammatory behaviors such as inhibitory adhesion ability and anti-angiogenesis therapeutic effect in vitro, but also administer efficiently localizing to atherosclerotic plaque explaining by aortic samples from established ApoE-/- mice. Therefore, this study provided a theoretical basis of biomimetic nanodrug in the treatment of AS as well as an effective reference for the combined application of nanodrug and clinical drugs.

A correlation of thrombin generation assay and clot waveform analysis in patients on warfarin

ABSTRACT Objectives Thrombin generation assays and activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA), are some examples of global coagulation assays. Each modality evaluates different aspects of the clot forming process to globally define haemostasis with exclusive measurement parameters. Data on CWA are emerging, but its performance against other haemostatic assays is yet to be ascertained. This study evaluates the correlation between aPTT-based CWA and CAT parameters across a range of INR in warfarin-treated patients. Patients/Methods A prospective study consisting of patients on warfarin anticoagulation with varying INR levels. CWA and CAT were performed for the study subjects. Results 54 samples were included covering an INR range from 1.33–6.89, with a mean of 4.31 +/- 1.13. For CAT parameters, endogenous thrombin potential (ETP) and peak thrombin were assessed. Both unadjusted and adjusted (adjusted for final plateau transmittance) aPTT-based CWA were evaluated for parameters min1 (maximum velocity), min2 (maximum acceleration) and max2 (maximum deceleration). Peak thrombin showed significant correlation with all CWA parameters (min1: r = 0.435, P<0.001; min2: r = 0.485, P<0.001; max2: r = 0.578, P<0.001; adjusted min1: r = 0.734, P<0.001, adjusted min2: r = 0.693, P<0.001; adjusted max2: r = 0.751, P<0.001). ETP correlated significantly with all CWA parameters except unadjusted min1 (min1: r = 0.235, P = 0.087; min2: r = 0.326, P = 0.016; max2: r = 0.437, P<0.001; adjusted min1: r = 0.610, P<0.001, adjusted min2: r = 0.563, P<0.001; adjusted max2: r = 0.642, P<0.001). Conclusion We demonstrated a modest correlation between CAT and CWA parameters. Adjusted CWA improved this correlation. These findings provide additional understanding of CWA and it’s role in the evaluation of global haemostatic function.

Adherence is an optimal factor for maximizing the effective and safe use of oral anticoagulants in patients with atrial fibrillation

Few studies assessed the association between major adverse cardiovascular events and adherence to warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of adherence to oral anticoagulants (OACs) in patients with AF using claims data (July 2014–April 2019). Using the initial 3-month medication possession rate (MPR), patients were categorized into adherent (MPR ≥ 0.8) or non-adherent (MPR < 0.8) groups. Propensity score matching of non-adherent group to adherent group was conducted for warfarin (1:1) and DOAC (1:3), respectively. Incidence of ischemic stroke, myocardial infarction (MI), intracranial hemorrhage, and all-cause death was assessed in the matched cohort (67,147 patients). The hazard ratio (HR) for adherence to OAC was estimated using the Cox proportional hazard model with adjusting covariate including age and sex. The risk for ischemic stroke, MI, and all-cause death was lower in the DOAC adherent group than in the DOAC non-adherent group (HR: 0.78; 95% confidence intervals: 0.73–0.84; 0.75, 0.60–0.94; 0.54, 0.51–0.57, respectively). Adherence to OAC was not associated with the risk of intracranial hemorrhage (1.01, 0.85–1.20). Commitment programs to improve adherence in patients with AF could maximize drug effectiveness and safety.

Long-term anticoagulation is associated with type II endoleaks and failure of sac regression after endovascular aneurysm repair

ObjectiveWithin the context of endovascular aneurysm repair (EVAR), the role of anticoagulation therapy on endoleak development and subsequent reintervention is unclear with conflicting data in the literature. The hypothesis of this study is that long-term anticoagulation is associated with persistent type II endoleaks and failure of sac regression in patients undergoing endoluminal repair of intact infrarenal aortic aneurysm. MethodsRetrospective cohort abstracted from the Vascular Quality Initiative index hospitalization and long-term follow-up datasets for EVAR (2003-2017) were included in the analysis. Patients not taking aspirin preoperatively and postoperatively were excluded. Patients taking anticoagulation and aspirin concomitantly (treatment) after the index procedure were compared against patients taking aspirin alone (control). Anticoagulation included warfarin and novel oral anticoagulants, including factor Xa inhibitors and direct thrombin inhibitors. One-to-one greedy matching using propensity scores was implemented to match patients. The primary end points were failure of aneurysm sac regression, sac expansion, risk of endoleak, and reintervention rate for endoleak at follow-up. Sac regression was defined as a decrease of at least 5 mm and sac expansion was defined as an increase of at least 5 mm. ResultsThere were 9004 patients who received ASA alone and 332 patients who received ASA and anticoagulation. Propensity scores were used to create 301 matching pairs to account for differences in baseline characteristics and comorbidities, including but not limited to age, sex, smoking, coronary artery disease, heart failure, and chronic kidney disease between the treatment and control groups. After adjusting for covariables anticoagulation use was independently associated with a significantly decreased abdominal aortic aneurysm sac regression (41.59% vs 58.41%; P = .001), but no statistically significant difference in sac expansion with long-term anticoagulation use (9.7% vs 4.9%; P = .056). There was increased risk of type II endoleaks (11.96% vs 6.31%; P = .023; relative risk, 1.89; 95% confidence interval, 1.11-3.23; P = .016), but no significant differences in type I, III, or indeterminate endoleaks. There was no statistical difference in 2-year reintervention rates (4.32% vs 2.66%; hazard ratio, 1.43; 95% confidence interval, 0.55-3.77; P = .461). There were no differences in any primary outcome between warfarin and novel oral anticoagulants. ConclusionsThese data demonstrate that long-term aspirin plus anticoagulation use is associated with a lack of aortic sac reduction and persistent type II endoleak, but not an increased risk for subsequent reintervention. Because prior studies have demonstrated that sac regression is a correlate of survival, these findings associating regression failure suggest a potential therapeutic failure for patients undergoing EVAR who also require long-term anticoagulation therapy. Although not a contraindication, long-term anticoagulation should be considered when counseling patients with a surgical indication aortic aneurysm.

The Transcultural Adaptation and Validation of the Chinese Version of the Duke Anticoagulation Satisfaction Scale.

Background: The Duke Anticoagulation Satisfaction Scale (DASS) offers a method to measure the quality of life and satisfaction of patients taking oral anticoagulants. The study aimed to validate the Chinese version of the DASS in Chinese patients on anticoagulation therapy. Methods: The DASS was translated, back-translated, and transculturally adapted into the Chinese version and then administered to participants taking oral anticoagulants in a physician–pharmacist collaborative anticoagulation clinic at a tertiary teaching hospital from October 2019 to December 2020. Reliability was analyzed through Cronbach’s alpha (α) and split-half reliability. Confirmatory factor analysis was performed to test the structural validity of the scale. Exploratory factor analysis was performed for items in the scales using the varimax rotation method. Results: A total of 189 patients completed the Chinese version of the DASS. Four dimensions and 23 items were included, with Cronbach’s α values of 0.89, 0.81, 0.89, and 0.74 for limitations on physical activities, diet restrictions, hassles and burdens, and positive psychological effect, respectively. Cronbach’s α coefficient of whole scale was 0.91. The split-half reliability of this scale is 0.747 (>0.7). Conclusion: The Chinese version of the DASS indicated excellent reliability and validity, compared to the original version. It could provide a practical instrument for healthcare practitioners to evaluate satisfaction and quality of life for anticoagulated patients in China. The difference in quality of life between patients taking warfarin and novel oral anticoagulants (NOACs) needs to be further explored in future studies.

Oral anti-coagulant treatment patterns in atrial fibrillation patients diagnosed with cancer: A Danish nationwide cohort study.

Data on the use of oral anti-coagulants (OAC) for stroke prevention in cancer patients with atrial fibrillation (AF) are sparse. Nationwide cohort study of patients with AF (2012-2018) and an indication for OAC who were diagnosed with cancer at least one year later (N=12 756). We identified treatment with OAC at cancer diagnosis and the following year and described the incidence of discontinuing or switching between warfarin and direct oral anti-coagulants (DOACs). We also described baseline characteristics associated with OAC non-persistence. One third of the cancer patients received no OAC therapy, whereas 42% received warfarin and 24% received DOAC treatment. Switching incidence between OACs was higher for those receiving warfarin treatment (8.6%) than DOAC treatment (1.7%) within one year. Treatment discontinuation was 61% for warfarin and 26% for DOAC. Females were less likely to discontinue DOAC than males (ratio 0.77, 95% confidence interval: 0.66, 0.90). Increasing cancer stage was associated with discontinuation of DOAC, but not warfarin. OAC for stroke prevention in AF was used by two thirds of patients with newly diagnosed cancer. Switching between OACs and discontinuation was more common for warfarin than DOAC, and females had higher persistence with DOACs.

Relationship of warfarin versus DOACs with thrombogenic milieu in the left atrium among patients with nonvalvular atrial fibrillation

AbstractBackgroundThrombogenic milieu (TM) within the left atrium plays a pivotal role in the pathogenesis of thromboembolic events, for which anticoagulation treatment is indicated typically on the mandatory basis. Little is known, however, about which regimen of anticoagulation, warfarin or direct oral anticoagulants (DOACs), is more likely associated with TM. We evaluated relative relationship of the two treatment options with concurrently‐observed TM in patients with nonvalvular atrial fibrillation (AF) who underwent transesophageal echocardiography.MethodsTM was defined as the presence of either left atrial spontaneous echo contrast (SEC) or thrombus, or both. To determine which regimen was more likely related to TM, we firstly compared the prevalence of TM in 208 patients taking warfarin (Warfarin group) versus 486 patients taking DOACs (DOAC group); and secondly, did the same analysis after propensity score matching.ResultsWarfarin group was more likely associated with TM compared with DOAC group (46% vs 29%, p &lt; 0.001). Similar findings were observed for dense SEC (18% vs 7%, p &lt; 0.001) and thrombus (4% vs 1%, p = 0.057). The propensity score matching (198 patients for each group), where several baseline parameters were matched including age, gender, chronicity of AF, estimated glomerular filtration rate and B‐type natriuretic peptide as well as the left ventricular ejection fraction, resulted in similar findings to the original groups (TM, 47% vs 32%, p = 0.002; dense SEC, 18% vs 7%, p = 0.001; thrombus, 4% vs 1%, p = 0.047).ConclusionsThis study may strengthen the data on randomized trials that DOACs are superior to warfarin in preventing thromboembolic events in nonvalvular AF patients. Further studies are required to elucidate the details behind this difference.

Stuck mechanical valve complication in non-COVID-19 patients during COVID-19 pandemic: single center experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Stuck valve is a very rare and severe complication that occurs in mechanical valve replacement patients with ineffective anticoagulation. However, with COVID-19 restriction measures, it became challenging to regularly assess INR to make sure it falls within the target therapeutic range to prevent this complication. Purpose We wanted to explore how did the COVID-19 pandemic restrictions impacted mechanical valve replacement patients on chronic anticoagulation and the long-term consequences of limiting their access to health service. Methods We present a series of 10 patients on warfarin anticoagulation therapy who either underwent transthoracic echocardiography for a suspected stuck valve or were seen at the outpatient valve clinic with the residual consequences of a stuck valve during the COVID-19 restriction measures in our institute. Results Eight patients were female, two of whom were pregnant at the first trimester and eventually went on to receive an abortion; six patients received urgent valve replacement cardiac surgery; four patients were managed medically e.g. with heparin; none had thrombolytic therapy. Stuck prosthetic valves incident has increased significantly during this period, particularly those in the mitral position for which urgent replacement and prolonged hospitalization including intensive care admission, with high in-hospital mortality rates and high costs were necessary. Mean hospital admission time was 27.5 ± 18.5 days. The cost of treatment, as average estimated reimbursement, was 11,000 USD for medical admission only, and 43,200 USD when surgery was required, up to 64,000 USD when ECMO was part of patient management. Conclusion Despite governments’ efforts to implement telemedicine and virtual clinics, COVID-19 restrictions and health-messaging affected the routine follow-up of non-COVID-19 patients. We report dramatic consequences to this drastic change in healthcare: clinical complications, lost lives and inflated healthcare costs in patients with a prosthetic valve. We believe that non-COVID-19 patients have paid, and will continue to pay in the future, a price that is much greater than those patients who have suffered from COVID-19. Active engagement of patients should be implemented in a time of emergencies, and further studies should address the efficacy and cost-effectiveness of public policies aimed to decrease the burden of avoidable complications and missed diagnoses. Abstract Figure. Fluoroscopy in a 70 years old patient

Warfarin versus direct oral anticoagulants for patients needing distal deep vein thrombosis treatment

ObjectiveGreat interest exists in standardizing the anticoagulant choice for patients requiring treatment of distal deep vein thrombosis (DDVT). In the present multicenter, retrospective cohort study, we evaluated the outcomes of patients with DDVT who had been treated with warfarin vs direct oral anticoagulants (DOACs; ie, rivaroxaban, apixaban, edoxaban, dabigatran). MethodsQueries were built for the TriNetX database (TriNetX LLC, Cambridge, Mass), a federated network of healthcare organizations across the United States that provides de-identified patient data through aggregated counts and statistical summaries. International Classification of Diseases, 10th revision, diagnostic codes were used to identify eligible patients. Data from January 1, 2013 to January 1, 2020 were reviewed. Statistical analyses, including propensity matching, were performed using TriNetX’s internal software. The inclusion criterion was treatment with either warfarin or a DOAC started within the first 24 hours of diagnosis of an isolated thrombosis of the following veins: anterior tibial, posterior tibial, peroneal, or calf muscular veins. The exclusion criteria were a history of an adverse reaction to anticoagulant agents, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, thrombophilia, mechanical heart valve, chronic proximal DVT (PDVT) and/or DDVT, and 6-month history of the following: acute PDVT, pulmonary embolism (PE), or anticoagulant usage. The outcomes measured included the incidence of mortality, PE, PDVT, stroke, myocardial infarction, and major bleeding within 6 months after initiating anticoagulation therapy. ResultsIn a cohort of 6509 patients, 1570 were treated with warfarin and 4939 were treated with a DOAC drug. After propensity matching for age, sex, ethnicity, and comorbidities, the DOAC cohort had a significantly lower incidence of PE (1.795% vs 3.590%; P = .0020) and major bleeding (7.949% vs 10.513%; P = .0134). Differences in the incidence of mortality, PDVT, myocardial infarction, and stroke were not statistically significant. ConclusionsBefore the present study, no strong evidence was available to suggest an optimal treatment modality for DDVT requiring anticoagulation therapy. The data from the present study suggest that patients receiving DOACs for the treatment of DDVT will have significantly lower rates of progression to PE and a lower incidence of major bleeding compared with patients receiving warfarin. This suggests that DOACs are superior to warfarin for treatment of DDVT.

Risk factors associated with post-extraction bleeding in patients on warfarin or direct-acting oral anticoagulants: a retrospective cohort study.

The purpose of this study was to investigate the risk factors associated with post-extraction persistent bleeding in patients on warfarin or direct-acting oral anticoagulants (DOACs) and the ability of risk scores to predict post-extraction bleeding. Three hundred ninety-one patients taking warfarin or DOACs underwent tooth extractions. Various risk factors for post-extraction bleeding, including number of tooth extraction, with antiplatelet therapy, and risk scores, were investigated by univariate and multivariate analyses. A post-extraction bleeding was classified into grades 1-3. The incidence of post-extraction bleeding was 26.8% (77 out of 287 patients; grade 1: 63, grade 2:14) in patients taking warfarin, and 26.0% (27 out of 104 patients; grade 1: 20, grade 2:7) in patients taking warfarin DOACs. Multivariate analyses showed that multiple teeth extractions and HAS-BLED scores (above 3 points) in patients taking warfarin, and only multiple teeth extractions in patients taking DOAC, were significantly associated with post-extraction bleeding, respectively. Most of the post-extraction bleedings were grade 1, which can be stopped by eligibly pressing gauze by surgeons. If patients taking anticoagulants are scheduled to undergo multiple teeth extractions or their HAS-BLED score are above 3 points (if warfarin), we recommend informing patients risk of post-extraction bleeding before operation, taking carefully hemostasis, and instructing patients to bite down accurately on the gauze for longer than usual.

Economy- and Social-Based Strategies for Anticoagulation of Patients with Atrial Fibrillation.

ResumoFundamento:A fibrilação atrial é um problema de saúde pública associado com um risco cinco vezes maior de acidente vascular cerebral e mortalidade. A análise de custos é importante para a introdução de novas terapias, e deve ser reconsiderada em situações especiais, tais como a pandemia do coronavírus em 2020.Objetivo:Avaliar os custos (em um período de um ano) relacionados à terapia anticoagulante e a qualidade de vida de pacientes com fibrilação atrial tratados em um hospital público universitário.Métodos:Os custos do paciente foram aqueles relacionados à anticoagulação e calculados pela média de custos mensais da varfarina ou de anticoagulantes orais diretos (DOACs). As despesas não médicas, como alimentação e transporte, foram calculadas a partir de dados obtidos de questionários. O questionário brasileiro SF-6D foi usado para medir a qualidade de vida. Valores p<0,05 foram considerados estatisticamente significativos.Resultados:A população do estudo consistiu em 90 pacientes, 45 em cada braço (varfarina vs. DOACs). Os custos foram 20% mais altos no grupo dos DOACs (US$55 532,62 vs. US$46 385,88), e principalmente relacionados ao preço dos medicamentos (US$23 497,16 vs. US$1903,27). Os custos hospitalares foram mais altos no grupo da varfarina (US$31 088,41 vs $24 604,74), e relacionados às visitas ao ambulatório. Ainda, as despesas não médicas foram duas vezes maiores no grupo varfarina ($13 394,20 vs $7 430,72). A equivalência de preço entre os dois medicamentos seria alcançada por uma redução de 39% no preço dos DOACs. Não foram observadas diferenças quanto à qualidade de vida.Conclusões:Os custos totais foram mais altos no grupo de pacientes tratados com DOACs que no grupo da varfarina. No entanto, uma redução de cerca de 40% no preço dos DOACs tornaria viável a incorporação desses medicamentos no sistema de saúde público brasileiro.

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.

The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied. The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin. We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs. DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.

Incidence of Venous Thromboembolism: The 3rd Korean Nationwide Study.

BackgroundThe incidence of venous thromboembolism (VTE) has gradually increased in the Korean population. This study aimed to evaluate the annual age- and sex-adjusted incidence rates (ASR) of VTE and anticoagulation trends between 2014 and 2018.MethodsUsing the Korean Health Insurance Review and Assessment Service database, we retrospectively identified VTE patients between 2014 and 2018 using both diagnostic and medication anticoagulant codes assigned within 6 months of the initial index event. Anticoagulant patterns were classified as follows: direct oral anticoagulants (DOAC), parenteral anticoagulants, warfarin, and mixed anticoagulation regimens.ResultsWe identified 95,205 patients with VTE (female, 56.8%). The ASR for VTE per 100,000 person-years increased from 32.8 in 2014 to 53.7 cases in 2018 (relative risk of 1.63; 95% confidence interval, 1.6–1.67). The VTE incidence rates were 25 times higher in the ≥ 80 group than in the 30s group. VTE occurred 1.29 times more often in women than in men. The proportion of DOAC prescriptions increased from 40.5% to 72.8%, whereas warfarin prescriptions decreased from 27% to 5.6% in 2014 and 2018.ConclusionIn Korea, the ASRs of VTE continued to increase since 2014, but the rate of increase slowed in 2018. The VTE occurred more often in the elderly and in women. Five years after the introduction of DOACs in 2013, they accounted for 73% of all anticoagulants used to treat VTE.