Treatment standards for direct oral anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation: A survey among German stroke units.

BACKGROUND: Acute ischemic stroke (AIS) in patients with non-valvular atrial fibrillation (AF) despite oral anticoagulation (OAC) is a complex and insufficiently investigated setting. Potential strategies range from maintaining the current OAC to changing the substance class. We have queried the specific treatment standards on German stroke units (SUs). METHODS: By means of a standardized online questionnaire via SurveyMonkey™ (San Mateo, CA, USA), all clinical heads of German SUs were asked about their treatment standards in the following clinical situations: first AIS of an OAC-naïve AF patient, AF patient with AIS despite administration of a vitamin K antagonist (VKA), AF patient with AIS despite administration of direct OAC (DOAC). In addition, the performance of specific coagulation tests in AF patients with AIS despite OAC was queried. RESULTS: 160 (48%) clinical heads of German SU responded. Data from pivotal trials (84%), own experience with substances (71%), and side-effect profiles (66%) determine the initial DOAC prescription. In case of an AIS despite OAC, 83 and 18% would switch from VKA to DOAC under certain conditions and always, respectively. Half of respondents would switch from DOAC to VKA under certain conditions, while the other half would decline. 96% would switch to an alternative DOAC. The vast majority of those who made preconditions considered concomitant diseases (92, 90, and 81%, respectively). Few would consider infarct pattern (<35%). 61% perform initial coagulation tests (only one-third substance-specific assessments); however, the majority do not use these to make further decisions. CONCLUSIONS: In the setting of an OAC-naïve AF patient with AIS, established pivotal data are most respected. In the unclear setting of an AIS despite OAC, most respondents consider concomitant diseases and give preference to switching to a (different) DOAC.

Assessment of Trends in Guideline-Based Oral Anticoagulant Prescription for Patients With Ischemic Stroke and Atrial Fibrillation in China.

Importance: Adherence to oral anticoagulants (OACs) per guideline recommendations is crucial in reducing ischemic stroke and systemic thromboembolism in high-risk patients with ischemic stroke and atrial fibrillation. However, data on OAC use are underreported in China. Objective: To assess adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescription of OACs, the temporal improvement in adherence, and the risk factors associated with OAC prescriptions. Design, Setting, and Participants: This quality improvement study was conducted at 1430 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with ischemic stroke and atrial fibrillation enrolled in the CSCA between August 1, 2015, and July 31, 2019. Exposure: Calendar year. Main Outcomes and Measures: Adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescribing of OACs (warfarin and non-vitamin K OACs, including dabigatran, rivaroxaban, apixaban, and edoxaban) at discharge. Results: Among 35 767 patients (18 785 women [52.5%]; mean [SD] age, 75.5 [9.2] years) with previous atrial fibrillation at admission, the median CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score was 4.0 (interquartile range, 3.0-5.0); 6303 (17.6%) were taking OACs prior to hospitalization for stroke, a rate that increased from 14.3% (20 of 140) in the third quarter of 2015 to 21.1% (118 of 560) in the third quarter of 2019 (P < .001 for trend). Of 49 531 eligible patients (26 028 men [52.5%]; mean [SD] age, 73.4 [10.4] years), 20 390 (41.2%) had an OAC prescription at discharge, an increase from 23.2% (36 of 155) in the third quarter of 2015 to 47.1% (403 of 856) in the third quarter of 2019 (P < .001 for trend). Warfarin was the most commonly prescribed OAC (11 956 [24.2%]) and had the largest temporal increase (from 5.8% [9 of 155] to 20.7% [177 of 856]). Older age (adjusted odds ratio [aOR] per 5 year increase, 0.89;95% CI, 0.89-0.90), lower levels of education (aOR for below elementary school, 0.84; 95% CI, 0.74-0.95 ), lower income (aOR for ≤¥1000 [$154], 0.66; 95% CI, 0.59-0.73), having new rural cooperative medical scheme insurance (aOR, 0.92; 95% CI, 0.87-0.96), prior antiplatelet use (aOR, 0.70; 95% CI, 0.66-0.74), having several cardiovascular comorbid conditions (including stroke or transient ischemic attack [aOR, 0.78; 95% CI, 0.75-0.82], hypertension [aOR, 0.84; 95% CI, 0.80-0.89], diabetes [aOR, 0.91; 95% CI, 0.83-0.99], dyslipidemia [aOR, 0.87; 95% CI, 0.80-0.94], carotid stenosis [aOR, 0.83; 95% CI, 0.69-0.98], and peripheral vascular disease [aOR, 0.80; 95% CI, 0.71-0.90]), and admission to secondary hospitals (aOR, 0.71; 95% CI, 0.68-0.74) or hospitals located in the central region of China (aOR, 0.80; 95% CI, 0.75-0.84) were associated with not being prescribed an OAC at discharge. Conclusions and Relevance: This quality improvement study suggests that, despite significant improvement over time, OAC prescriptions remained low. Efforts to increase OAC prescriptions, especially non-vitamin K OACs, are needed for vulnerable subgroups by age, socioeconomic status, and presence of comorbid conditions.

Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation. DESIGN: Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019. SETTING: A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center. PATIENTS: Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications. CONCLUSIONS: When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.

Anti-Xa activity and hemorrhagic events under extracorporeal membrane oxygenation (ECMO): a multicenter cohort study.

BACKGROUND: Hemorrhagic events remain a major concern in patients under extracorporeal membrane oxygenation (ECMO) support. We tested the association between anticoagulation levels and hemorrhagic events under ECMO using anti-Xa activity monitoring. METHODS: We performed a retrospective multicenter cohort study in three ECMO centers. All adult patients treated with veno-venous (VV)- or veno-arterial (VA)-ECMO in 6 intensive care units between September 2017 and August 2019 were included. Anti-Xa activities were collected until a hemorrhagic event in the bleeding group and for the duration of ECMO in the non-bleeding group. All dosages were averaged to obtain means of anti-Xa activity for each patient, and patients were compared according to the occurrence or not of bleeding. RESULTS: Among 367 patients assessed for eligibility, 121 were included. Thirty-five (29%) presented a hemorrhagic complication. In univariate analysis, anti-Xa activities were significantly higher in the bleeding group than in the non-bleeding group, both for the mean anti-Xa activity (0.38 [0.29-0.67] vs 0.33 [0.22-0.42] IU/mL; p = 0.01) and the maximal anti-Xa activity (0.83 [0.47-1.46] vs 0.66 [0.36-0.91] IU/mL; p = 0.05). In the Cox proportional hazard model, mean anti-Xa activity was associated with bleeding (p = 0.0001). By Kaplan-Meier analysis with the cutoff value at 0.46 IU/mL obtained by ROC curve analysis, the probability of survival under ECMO without bleeding was significantly lower when mean anti-Xa was > 0.46 IU/mL (p = 0.0006). CONCLUSION: In critically ill patients under ECMO, mean anti-Xa activity was an independent risk factor for hemorrhagic complications. Anticoagulation targets could be revised downward in both VV- and VA-ECMO.

Thrombotic complications with interruption of direct oral anticoagulants in dermatologic surgery.

BACKGROUND: Direct oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran, are increasingly being used to provide prophylaxis and treatment for arterial and venous thromboembolism. Multiple procedural subspecialties have implemented guidelines detailing time frames for perioperative DOAC interruption; however, the impact of perioperative DOAC interruption in patients undergoing dermatologic surgery is currently unknown, and evidence-based guidelines are lacking. OBJECTIVE: To assess the 30-day postoperative rate of thrombotic complications (ischemic stroke, transient ischemic attack, systemic embolism, deep vein thrombosis [DVT] and pulmonary embolism) in patients with nonvalvular atrial fibrillation (AF) or a history of DVT who underwent perioperative DOAC interruption during dermatologic surgery. METHODS: A retrospective medical record review was performed of all patients with AF or a history of DVT who underwent perioperative DOAC interruption during dermatologic surgery at Advanced Dermatologic Surgery and the University of Kansas Medical Center between January 1, 2016, and August 31, 2020. RESULTS: Among 806 operations, comprising 750 Mohs micrographic operations (93.1%) and 56 excisions (6.9%), 1 patient (0.14% of patients with AF) sustained a transient ischemic attack and 2 patients (0.25% of all patients) sustained minor bleeding complications during the 30-day postoperative period. CONCLUSION: Perioperative DOAC interruption appears to be safe and efficacious in dermatologic surgery.

Special Considerations in Pulmonary Embolism: Clot-in-Transit and Incidental Pulmonary Embolism.

This article describes 2 relatively rare, but complex situations in pulmonary embolism (PE): clot-in-transit (CIT), incidental PE (IPE). CIT describes a venous thromboembolism that has become lodged in the right heart. CIT is associated with high mortality and presents unique challenges in management. Incidental PE (IPE) describes PE diagnosed on imaging performed for another indication. The treatment is complex because there is often a disconnect between the PE severity on imaging and lack of severity of the clinical presentation. We summarize the available literature and aid clinicians as they manage patients with PE across the clinical severity spectrum.

Evaluating Effectiveness and Safety in Chronic Kidney Disease with Atrial Flutter Using an Anticoagulation Strategy.

Background and Objectives: Recent randomized trials of oral antithrombotic drugs with atrial flutter (AFL) excluded patients with renal impairment because of their increased risk of bleeding. To date, no relevant studies have assessed the effectiveness and safety of different antithrombotic drugs in chronic kidney disease (CKD) patients with AFL. This cohort study evaluated the effectiveness and safety of different antithrombotic drugs in CKD patients with AFL. This study also investigated the risk of cardiovascular events from antithrombotic drugs through different risk profiles of stroke stratified by the CHA2DS2-VASc score. Materials and Methods: This cohort study was performed in patients with AFL and CKD who were extracted from the National Health Insurance (NHI) Database in Taiwan. Oral antithrombotic therapy (oral anticoagulants (OAC) or antiplatelets (APT)) was administered to patients who had been diagnosed with AFL after being diagnosed with CKD between 2011 and 2015. Primary outcomes, including ischemic stroke, systemic embolism, and composite of stroke, and secondary outcomes, including major adverse cardiac events (MACEs), major bleeding, all-cause mortality, and cardiovascular-related death, were examined. Results: A total of 2468 patients were included in this study. The results showed no statistically significant differences in the risk of primary outcomes. For the secondary outcomes, there were also no statistically significant differences in the risk of MACEs and major bleeding. However, the pooled results indicated that the hazard ratio (HR) for all-cause mortality with OAC was 0.24 (95% confidence interval (CI) = 0.10-0.55) compared with combination therapy, and the HR for APT compared with OAC was 2.86 (95% CI = 1.48-5.53). Conclusions: In the studied population, OAC or APT alone were proved equally effective for stroke prophylaxis. Furthermore, OAC might reduce the all-cause mortality rate compared with APT and should be considered as the first choice of oral antithrombotic drugs in patients with AFL and CKD.

Prophylaxis of venous thromboembolism in general surgery in Spain. Analysis of a national survey. / Profilaxis del tromboembolismo venoso en cirugía general en España. Análisis de una encuesta nacional.

INTRODUCTION: Venous thromboembolism (VTE) represents a serious postoperative complication that can be prevented by adequate thromboprophylaxis. Surveys provide relevant information about clinician's attitudes and preferences regarding VTE prophylaxis. METHODS: Transversal, descriptive study based on a survey sent to general surgeons members of the Spanish Association of Surgeons (AEC), that included 31 questions regarding postoperative VTE and its prevention, as well as three clinical scenarios. RESULTS: 530 surgeons, 21.8% of the 2,429 invited by electronic mail to participate, completed the survey. Most of the answering clinicians work on in big teaching hospitals, and 28.5% are residents. VTE represents a serious problem for 28% of participants. Although 81% consider that their knowledge on the prevention of postoperative VTE is adequate, a similar percentage recognizes the need for further education. The vast majority (98.7%) use low molecular weight heparins, which are considered the most effective and safe modality, followed by mechanical methods. The Caprini risk assessment score is used by 81% of surgeons, who usually start pharmacological prophylaxis preoperatively. However, there are remarkable differences in the dosing of heparins, timing of initiation, and duration, especially in non-oncologic surgical patients. CONCLUSIONS: Most Spanish surgeons are interested in the prevention of postoperative VTE. Overall, the level of knowledge on thromboprophylaxis is adequate. However, our results indicate that there is a need for better education on relevant practical aspects of prophylaxis that could be achieved by incorporating recommendations from recent guidelines to local hospital-based protocols.

Thrombosis: Risk Factors Among Pediatric Patients With Cancer.

BACKGROUND: Thrombosis is the formation of a blood clot, or thrombus, inside of a blood vessel. Pediatric patients with cancer are at a higher risk of developing a thrombus because of their underlying disease, as well as their treatment and supportive care. Thrombosis can lead to significant morbidity, such as pulmonary embolism, in pediatric patients with cancer. OBJECTIVES: The purpose of this study is to identify risk factors for developing a thrombus among pediatric patients with cancer, along with treatment and prevention protocols. This study also examines the clinical nurse's role in preventing thrombosis and caring for pediatric patients who present with thrombosis. METHODS: The thrombosis literature was reviewed to identify risk factors, treatment regimens, and strategies for prevention. FINDINGS: Thrombosis in pediatric patients with cancer requires management of potential complications so that cancer treatment may continue.

Thirty-day mortality in atrial fibrillation patients with gastrointestinal bleeding in the emergency department: differences between direct oral anticoagulant and warfarin users.

More clinical data are required on the safety of direct oral anticoagulants (DOACs). Although patients treated with warfarin and DOACs have a similar risk of bleeding, short-term mortality after a gastrointestinal bleeding (GIB) episode in DOAC-treated patients has not been clarified. The objective of this study was to assess differences in 30-day mortality in patients treated with DOACs or warfarin admitted to the emergency department (ED) for GIB. This was a multicentre retrospective study conducted over 2 years. The study included patients evaluated at three different EDs for GIB. The baseline characteristics were included. Subsequently, we assessed the differences in past medical history and clinical data between the two study groups (DOAC and warfarin users). Differences between the two groups were evaluated using Kaplan-Meier curves. Among the 284 patients presenting GIB enrolled in the study period, 39.4% (112/284) were treated with DOACs and 60.6% (172/284) were treated with warfarin. Overall, 8.1% (23/284) of patients died within 30 days. Among the 172 warfarin-treated patients, 8.7% (15/172) died within 30 days from ED evaluation. In the 112 DOAC-treated patients, the mortality rate was 7.1% (8/112). The Cox regression analysis, adjusted for possible clinical confounders, and the Kaplan-Meier curves did not outline differences between the two treatment groups. The present study shows no differences between DOACs and warfarin in short-term mortality after GIB.

Biosimilars of low molecular weight heparins: Relevant background information for your drug formulary.

Biosimilars of low molecular weight heparins (LMWHs) are more alike the originator than different branded LMWHs. The latter differ largely in molecular weight, anti-FXa/anti-FIIa ratio and antithrombin binding. The Food and Drug Administration and European Medicines Agency guidelines are sufficient for the clinical use of high quality LMWHs. However, the Food and Drug Administration guideline lacks the results of a phase I clinical trial in the approval process. Most information about biosimilars is available for enoxaparin given that many biosimilars of enoxaparin have received market access. The guidelines of many International Thrombosis Societies for LMWH biosimilars are too stringent, not updated and impractical for formulary uptake discussions. This review gives background information on critical factors for the formulary uptake process of LMWHs with special attention for the use of the System of Objectified Judgment Analysis/Infomatrix model.

The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis.

Few prospective studies have reported the cumulative incidence of venous thromboembolism (VTE) in the intensive care unit (ICU), especially for patients receiving guideline-recommended VTE prophylaxis. We aimed to design a prospective observational study to investigate the cumulative incidence and risk factors of ICU-acquired VTE for those populations.We prospectively studied 281 consecutively included patients in the ICU at a single center. All patients provided informed consent. Patients received ultrasound evaluation and were followed for VTE before ICU discharge or within 28 days of ICU stay. The type of VTE thromboprophylaxis was also recorded for all patients. Variables from univariate analyses that were associated with VTE were included in the binary logistic regression analysis to determine VTE predictors. The cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan-Meier methods.Patients had a median age of 60 years (range, 18-89) and an acute physiology and chronic health evaluation II score of 17 (range, 4-36). Despite all patients receiving guideline-recommended thromboprophylaxis, the cumulative incidence of VTE at 7, 14, 21, and 28 days was 4.45% (95% CI 2.55-7.71), 7.14% (95% CI 4.61-10.97), 7.53% (95% CI 4.92-11.43), and 9.55% (95% CI 6.55-13.81), respectively. Central venous catheter use (P = .002, odds ratio [OR] = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the incidence of VTE for patients admitted to the ICU.Our prospective observational study found that the 28-day cumulative incidence of VTE was relatively high for patients admitted to the ICU, despite the use of guideline-recommended thromboprophylaxis. Patients with femoral central venous catheter, prolonged ICU length of stay, or a high Caprini score may have an increased risk of developing VTE.

Physicians' Perceptions of Their Patients' Attitude and Knowledge of Long-Term Oral Anticoagulant Therapy in Bulgaria.

Background and Objectives: Oral anticoagulation (OAC) is widely used in daily clinical practice worldwide for various indications. We aimed to explore the perception of Bulgarian clinicians about their patients' attitude and knowledge of long-term OAC, prescribed for atrial fibrillation (AF) and/or known deep venous thrombosis (DVT)/pulmonary embolism (PE). Materials and Methods: We performed a cross-sectional study that involved 226 specialists: 187 (82.7%) cardiologists, 23 (10.2%) neurologists, and 16 (7.1%) vascular surgeons. They filled in a questionnaire, specially designed for our study, answering various questions regarding OAC treatment in their daily clinical practice. Results: The mean prescription rate of OACs in AF patients was 80.3% and in DVT/PE-88.6%. One hundred and eighty-seven (82.7%) of the participants stated they see their patients on OAC at least once per month. According to more than one-third of the inquired clinicians, the patients did not understand well enough the provided information concerning net clinical benefit of OAC treatment. About 68% of the clinicians declared that their patients would prefer a "mutual" approach, discussing with the physician the OAC options and taking together the final decision, whereas according to 43 (19.0%), the patients preferred the physician to take a decision for them. Patients' OAC treatment had been interrupted at least once within the last year due to a physician's decision by 178 (78.8%) of the participants and the most common reason was elective surgery. The most influential factors for a patient's choice of OAC were the need of a specific diet to be kept, intake frequency, and possible adverse reactions. Conclusions: Our results suggest that a clinician's continuous medical education, shared decision-making, and appropriate local strategies for improved awareness of AF/DVT/PE patients are key factors for improvement of OAC management.

Thromboprophylaxis After Hospitalization for Joint Replacement Surgery.

Venous thromboembolism (VTE) is a leading cause of mortality during the perioperative period, with individuals who have undergone hip and knee arthroplasty at the highest risk for VTE. The American College of Chest Physicians recommends 35 days of postoperative thromboprophylaxis and the use of intermittent pneumatic compression (IPC) therapy for mechanical compression after major orthopedic surgery. However, little research has described adherence to these recommendations during recovery at home. The purpose of this cross-sectional descriptive study was to describe thromboprophylaxis prescription, use, and education among patients discharged home after major orthopedic surgery. We surveyed patients within 2 years of major orthopedic surgery. A total of 388 subjects completed the survey. More than three-quarters of respondents reported a thromboprophylaxis duration <35 days. Most (93.8%) respondents were prescribed a pharmacologic agent, while 55.9% were prescribed mechanical compression therapy. Of the respondents who were prescribed mechanical compression therapy, 13.4% were prescribed IPC. Adherence to mechanical compression therapy was moderate, with 63% of respondents wearing mechanical compression therapy ≥75% of the time. The results of this study suggest a need for increased duration of thromboprophylaxis and increased use of IPC in the outpatient setting. Additional research describing prescribers' perceptions of thromboprophylaxis is also needed.

Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: Update and Periprocedural Management.

Vitamin K antagonists (eg, warfarin) have been the standard of care for stroke prophylaxis in atrial fibrillation. The direct oral anticoagulants dabigatran (direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (direct factor Xa inhibitors) are as efficacious as and in some instances superior to vitamin K antagonists in the prevention of stroke, systemic embolism, and major bleeding compared with warfarin for nonvalvular atrial fibrillation. Benefits of direct oral anticoagulants include a rapid onset of therapeutic effect, fixed dose-response relationships without the need for routine monitoring, a short half-life, and infrequent need for periprocedural bridging with a parenteral agent. However, direct oral anticoagulants differ in subsets of patients. Critical care and advanced practice nurses must understand these differences, prescribing considerations, drug aherence interventions, drug-drug interactions, and periprocedural management. This article presents an update and review of direct oral antigcoagulants based on the latest national guidelines.

A multicentre controlled pre-post trial of an implementation science intervention to improve venous thromboembolism prophylaxis in critically ill patients.

PURPOSE: To test whether a multicomponent intervention would increase the use of low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in critically ill patients and change patient outcomes and healthcare utilization. METHODS: Controlled pre-post trial of 12,342 adults admitted to 11 ICUs (five intervention, six control) May 1, 2015 to April 30, 2017 with no contraindication to pharmacological prophylaxis and an ICU stay longer than 24 h. Models were developed to examine temporal changes in ICU VTE prophylaxis (primary outcome), VTE, major bleeding, heparin-induced thrombocytopenia (HIT), death and hospital costs. RESULTS: The use of LMWH increased from 45.9% to 78.3% of patient days in the intervention group and from 37.9% to 53.3% in the control group, an absolute increase difference of 17.0% (32.4% vs. 15.4%, p = 0.001). Changes in the administration of UFH were inversely related to those of LMWH. There were no significant differences in the adjusted odds of VTE (ratio of odds ratios [rOR] 1.13, 95% CI 0.51-2.46) or major bleeding (rOR 1.22, 95% CI 0.97-1.54) post-implementation of the intervention (compared to pre-implementation) between the intervention group and the control group. HIT was uncommon in both groups (n = 20 patients). There were no significant changes for ICU and hospital mortality, length of stay and costs. Results were similar when stratified according to reason for ICU admission, patient weight and kidney function. CONCLUSIONS: A multicomponent intervention changed practice, but not clinical and economic outcomes. The benefit of implementing LMWH for VTE prophylaxis under real-world conditions is uncertain.

Extended-duration betrixaban versus shorter-duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients: an APEX trial substudy.

PURPOSE: To assess the efficacy and safety of betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. METHODS: The APEX trial randomized 7513 acutely ill hospitalized patients to betrixaban for 35-42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35-42 days and at 77 days. RESULTS: At 35-42 days, extended betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). CONCLUSIONS: Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration betrixaban had fewer VTE without more major bleeding events. The benefit of betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

A Review on the New and Old Anticoagulants.

Anticoagulants serve as the primary strategy for the prevention and treatment of both arterial and venous thromboembolism. Anticoagulants disrupt coagulation by interfering at various points in the coagulation cascade. This class of medications does not lyse clots that already exist; rather, it prevents thrombus formation and prevents or slows the extension of an existing clot. For decades, the standard therapy for patients requiring oral anticoagulation was warfarin. However, due to some of the shortcomings of warfarin, including the need for continuous routine monitoring, longtime onset and offset of anticoagulation effect, major food and drug interactions, and high incidence of bleeding, newer agents, termed direct oral anticoagulants, or DOACs were developed. This article will provide a review of clinically important information regarding the most commonly used anticoagulants and their reversal agents.