A multifaceted quality improvement intervention on venous thromboembolism prophylaxis compliance in hospitalized medical patients at a comprehensive cancer center.

INTRODUCTION: Previous studies suggest that quality improvement initiatives focused on hospital-acquired venous thromboembolism have a positive impact on prescribing rates of venous thromboembolism prophylaxis, especially those that incorporate computerized changes. METHODS: We conducted a quality improvement project to determine whether education and computerized prescriber order entry system changes affect venous thromboembolism prophylaxis compliance rates in hospitalized medical patients at a Comprehensive Cancer Center. Between 1 January 2021 and 31 January 2023, 37,739 non-surgical, adult patient encounters with a length of stay > 48 h were analyzed in our study. From 18 December 2021 to 8 March 2022, provider education was delivered to the three largest admitting services, and computerized prescriber order entry changes were implemented incorporating a mandatory requirement to either order venous thromboembolism prophylaxis or document a contraindication for all patients at moderate venous thromboembolism risk. RESULTS: Monthly venous thromboembolism prophylaxis compliance rates, as defined by the Centers for Medicare and Medicaid Services VTE-1 metric, increased from a mean of 74% to 93% after the interventions. This change was driven primarily by an increased utilization of mechanical venous thromboembolism prophylaxis from 37% to 53%. CONCLUSION: Our study demonstrated that a multi-faceted intervention incorporating provider education and computerized prescriber order entry system changes can significantly increase venous thromboembolism prophylaxis compliance rates in cancer patients.

Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization. METHODS: COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted D-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the D-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization. RESULTS: The primary efficacy outcome D-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population D-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline D-dimer > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15-1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups. CONCLUSIONS: Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by D-dimer > 2 ULN needs confirmation in further studies.

Preoperative Patient Optimization: Outcomes from Elective Total Joint Arthroplasty in a Large US Healthcare System.

INTRODUCTION: Patient factors are known to affect outcomes in arthroplasty surgery. A preoperative program to address modifiable factors may aid in more appropriate patient selection. We sought to assess patient selection and 90-day postoperative outcomes for total joint arthroplasty (TJA) candidates before and after implementation of a preoperative optimization protocol. METHODS: A retrospective time-trend study using data from an integrated healthcare system's total joint replacement registry was done. The study sample consisted of patients aged 18 years or older who underwent primary elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) for osteoarthritis between 2009 and 2019. Patients were divided into two cohorts: procedures performed from 2009 to 2013 ("preoptimization protocol") and those from 2015 to 2019 ("postoptimization protocol"); 2014 was excluded because an evidence-based preoperative patient optimization protocol was progressively implemented throughout the year. Patient characteristics, optimization factors, and 90-day outcomes (including emergency department [ED] visits, readmission, all-cause revision, deep infection, venous thromboembolism, and mortality) were compared between the two cohorts using the Pearson chi-square test or Wilcoxon test. RESULTS: The study sample included 25,925 THA and 60,484 TKA. In the THA cohort, 10,364 (40.0%) and 15,561 (60.0%) were from the preoptimization and postoptimization cohorts, respectively. The postoptimization THA cohort saw lower rates of ED visits (12.1% vs. 9.4%, P < 0.001) and readmissions (5.6% vs. 3.8%, P < 0.001). In the TKA cohort, 24,054 (39.8%) and 36,430 (60.2%) were from the preoptimization and postoptimization cohorts, respectively. The postoptimization TKA cohort saw lower rates of ED visits (13.1% vs. 11.9%, P < 0.001), readmissions (5.6% vs. 3.0%, P < 0.001), all-cause revisions (0.5% vs. 0.3%, P = 0.003), venous thromboembolism (1.3% vs. 0.9%, P < 0.001), and mortality (0.3% vs. 0.2%, P = 0.011). DISCUSSION: An evidence-based protocol to improve patient selection based on modifiable patient factors was adopted by orthopaedic surgeons in the system and utilization of the protocol before TJA was associated with fewer postoperative complications over time. LEVEL OF EVIDENCE: Level IV.

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update.

PURPOSE: To conduct an update of the ASCO venous thromboembolism (VTE) guideline. METHODS: After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022. RESULTS: Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding. RECOMMENDATIONS: Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. RECENT FINDINGS: Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19.

Importance: Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives: To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants: A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures: Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures: The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results: A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance: In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

Biological therapies in the prevention of maternal mortality.

Although the maternal mortality rate has decreased and significant improvements have been made in maternal care, maternal death remains one of the substantial problems of our society. The leading causes of maternal death are postpartum hemorrhage, the most important cause of death in developing countries, and preeclampsia and venous thromboembolism, which are more prevalent in developed countries. To treat these conditions, a variety of therapeutic approaches, including pharmacologic agents and surgical techniques, have been adopted. However, a certain number of pregnant women do not respond to any of these options. That is the main reason for developing new therapeutic approaches. Biological medications are isolated from natural sources or produced by biotechnology methods. Heparin is already successfully used in the therapy of deep venous thrombosis and pulmonary embolism. Blood derivatives, used in an autologous or allogenic manner, have proven to be efficacious in achieving hemostasis in postpartum hemorrhage. Mesenchymal stem cells, alpha-1-microglobulin, and antithrombin exhibit promising results in the treatment of preeclampsia in experimental models. However, it is essential to evaluate these novel approaches' efficacy and safety profile throughout clinical trials before they can become a standard part of patient care.

Prophylactic Anticoagulation in Patients With Pancreatic Adenocarcinoma: A Single Tertiary Care Center Retrospective QI Project.

BACKGROUND/AIM: A well-known complication of pancreatic adenocarcinoma (PDAC) is venous thromboembolism (VTE). The Khorana score is used as a tool to help determine the role of primary prophylaxis (PPx) in cancer patients with VTE. This study compared outcomes in PDAC patients who received primary PPx (anticoagulation) versus those who did not. PATIENTS AND METHODS: PDAC patients from 2017-2019 at Allegheny General Hospital were retrospectively reviewed. Descriptive statistics were presented via medians with interquartile ranges for continuous variables and percentages for categorical variables. Predictors of VTE development were determined using univariable and multivariable logistic regression models. T-tests and Chi-square tests were used to compare means and percentages, respectively. RESULTS: A total of 102 patients with full VTE PPx data were reviewed. At least one VTE event was identified in 29 patients (28.2%). A total of 4 out of these 29 patients (13.8%) were on PPx anticoagulation. Death secondary to VTE occurred in one patient without PPx. Two (2.0%) patients experienced bleeding events of those prescribed VTE PPx. On univariable analysis, stage IV disease, planned surgery, and unresectable disease were predictors of VTE development. On multivariate analysis, total pancreatectomy was a predictor of VTE development. There was no difference in average time to progression amongst patients who had developed VTE versus those who did not. CONCLUSION: The Khorana score for VTE PPx in PDAC patients in underutilized.

Trends and Risk Factors for Venous Thromboembolism Among Hospitalized Medical Patients.

Importance: While hospital-associated venous thromboembolism (HA-VTE) is a known complication of hospitalization, contemporary incidence and outcomes data are scarce and methodologically contested. Objective: To define and validate an automated electronic health record (EHR)-based algorithm for retrospective detection of HA-VTE and examine contemporary HA-VTE incidence, previously reported risk factors, and outcomes. Design, Setting, and Participants: This cohort study was conducted using hospital admissions between January 1, 2013, and June 30, 2021, with follow-up until December 31, 2021. All medical (non-intensive care unit) admissions at an integrated health care delivery system with 21 hospitals in Northern California during the study period were included. Data were analyzed from January to June 2022. Exposures: Previously reported risk factors associated with HA-VTE and administration of pharmacological prophylaxis were evaluated as factors associated with HA-VTE. Main Outcomes and Measures: Yearly incidence rates and timing of HA-VTE events overall and by subtype (deep vein thrombosis, pulmonary embolism, both, or unknown), as well as readmissions and mortality rates. Results: Among 1 112 014 hospitalizations involving 529 492 patients (268 797 [50.8%] women; 75 238 Asian [14.2%], 52 697 Black [10.0%], 79 398 Hispanic [15.0%], and 307 439 non-Hispanic White [58.1%]; median [IQR] age, 67.0 [54.0-79.0] years), there were 13 843 HA-VTE events (1.2% of admissions) occurring in 10 410 patients (2.0%). HA-VTE events increased from 307 of 29 095 hospitalizations (1.1%) in the first quarter of 2013 to 551 of 33 729 hospitalizations (1.6%) in the first quarter of 2021. Among all HA-VTE events, 10 746 events (77.6%) were first noted after discharge. In multivariable analyses, several factors were associated with increased odds of HA-VTE, including active cancer (adjusted odds ratio [aOR], 1.96; 95% CI, 1.85-2.08), prior VTE (aOR, 1.71; 95% CI, 1.63-1.79), and reduced mobility (aOR, 1.63; 95% CI, 1.50-1.77). Factors associated with decreased likelihood of HA-VTE included Asian race (vs non-Hispanic White: aOR, 0.65; 95% CI, 0.61-0.69), current admission for suspected stroke (aOR, 0.73; 95% CI, 0.65-0.81), and Hispanic ethnicity (vs non-Hispanic White: aOR, 0.81; 95% CI, 0.77-0.86). HA-VTE events were associated with increased risk of readmission (hazard ratio [HR], 3.33; 95% CI, 3.25-3.41) and mortality (HR, 1.63; 95% CI, 1.57-1.70). Conclusions and Relevance: This study found that HA-VTE events occurred in 1.2% of medical admissions, increased over time, and were associated with increased adverse outcomes. These findings suggest that approaches designed to mitigate occurrence and outcomes associated with HA-VTE may remain needed.

Comparison of real-world clinical and economic outcomes in patients receiving oral anticoagulants: A retrospective claims analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for the prevention of stroke in nonvalvular atrial fibrillation (AF) and for the treatment of venous thromboembolism (VTE). Warfarin, the standard of care prior to DOACs, requires monitoring and dose adjustment to ensure patients remain appropriately anticoagulated. DOACs do not require monitoring but are significantly more expensive. We sought to examine real-world effectiveness and costs of DOACs and warfarin in patients with AF and VTE. OBJECTIVE: To examine clinical and economic outcomes. The clinical objectives were to determine the bleeding and thrombotic event rates associated with DOACs vs warfarin. The economic objectives were to determine the cost associated with these events, as well as the all-cause medical and pharmacy costs associated with DOACs vs warfarin. METHODS: This analysis was an observational, propensity-matched comparison of retrospective medical and pharmacy claims data for members enrolled in an integrated health plan between October 1, 2015, and September 30, 2020. Members who were older than 18 years of age with at least 1 30-day supply of warfarin or a DOAC filled within 30 days of a new diagnosis of VTE or nonvalvular AF were eligible for the analysis. Cox hazard ratios were used to compare differences in clinical outcomes, where paired t-tests were used to evaluate economic outcomes. RESULTS: After matching, there were 893 patients in each group. Among matched members, warfarin was associated with increased risk of nonmajor bleeds relative to apixaban (hazard ratio [HR] = 1.526; P = 0.0048) and increased risk of pulmonary embolism relative to both DOACs (apixaban: HR = 1.941 [P = 0.0328]; rivaroxaban: HR = 1.833 [P = 0.0489]). No statistically significant difference was observed in hospitalizations or in length of stay between warfarin and either DOAC. The difference-in-difference (DID) in total costs of care per member per month for apixaban and rivaroxaban relative to warfarin were $801.64 (P = 0.0178) and $534.23 (P = 0.0998) more, respectively. DID in VTE-related cost for apixaban was $177.09 less, relative to warfarin (P = 0.0098). DID in all-cause pharmacy costs for apixaban and rivaroxaban relative to warfarin were $342.47 (P < 0.0001) and $386.42 (P < 0.001) more, respectively. CONCLUSIONS: Warfarin use was associated with a significant decrease in total cost of care despite a significant increase in VTE-related costs vs apixaban. Warfarin was also associated with a significant increase in other nonmajor bleeds relative to apixaban, as well as a significant increase in pulmonary embolism relative to both DOACs. Warfarin was associated with a significant reduction in all-cause pharmacy cost compared with either DOAC. DISCLOSURES: The authors of this study have nothing to disclose.

Aspirin versus Rivaroxaban to Prevent Venous Thromboembolism after Total Knee Arthroplasty: A Double-blinded, Randomized Controlled Trial / Aspirina versus rivaroxabana na prevenção do tromboembolismo venoso após artroplastia total do joelho: Um ensaio clínico randomizado, controlado e duplo-cego

Abstract Objective Aspirin (acetylsalicylic acid, ASA) and rivaroxaban are anticoagulants that have increased in popularity due to ease of use in the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). The present study aimed to evaluate the efficacy of ASA compared with that of rivaroxaban on VTE prophylaxis in patients who underwent TKA. Method Forty patients who had primary knee osteoarthritis and would undergo TKA were randomized into two groups. In total, 20 patients in the ASA group used oral aspirin, at a dose of 300 mg/day, for VTE prophylaxis after TKA, while 20 patients in the rivaroxaban group received oral rivaroxaban, at a dose of 10 mg/day. On days 4 and 14 after the operation, deep vein thrombosis (DVT) in the lower limbs on the operated side was detected through duplex ultrasonography. Other complications were recorded for 14 days. Results There were no positive findings of DVT detected with duplex ultrasonography in the groups of patients, and the occurrence of pulmonary embolism was not observed. In total, 4 patients had subcutaneous ecchymosis on the fourth postoperative day (2 patients in the ASA group and 2 patients in the rivaroxaban group; p= 1.0), and another 4 patients on the fourteenth postoperative day (1 patient in the ASA group and 3 patients in the rivaroxaban group; p= 0.292). No cases of wound hematoma, major organ bleeding, wound infection, or reoperation were observed in the sample. Conclusion Aspirin and rivaroxaban had comparable efficacy to prevent VTE, without increasing the incidence of wound complications and bleeding after TKA.

Resumo Objetivo A aspirina (ácido acetilsalicílico, AAS) e a rivaroxabana são anticoagulantes que vêm ganhando popularidade devido à facilidade de uso na prevenção do tromboembolismo venoso (TEV) após artroplastia total do joelho (ATJ). Este estudo teve como objetivo avaliar a eficácia do AAS em comparação com a da rivaroxabana na profilaxia de TEV em pacientes submetidos a ATJ. Método Quarenta pacientes com osteoartrite primária do joelho, que seriam submetidos a ATJ, foram randomizados em dois grupos. No total, 20 pacientes do grupo AAS usaram aspirina oral, na dose de 300 mg/dia, para a profilaxia do TEV após ATJ; e 20 pacientes do grupo rivaroxabana receberam uma dose oral de 10 mg/dia. No 4° e 14° dias do pós-operatório, trombose venosa profunda (TVP) dos membros inferiores no lado da cirurgia foi detectada por meio de ultrassonografia duplex. Foram registradas outras complicações durante catorze dias. Resultados Não foram detectados achados positivos de TVP com a ultrassonografia duplex nos grupos de pacientes, e não se observou a ocorrência de embolia pulmonar. No total, 4 pacientes apresentaram equimose subcutânea no 4° dia do pós-operatório (2 pacientes no grupo AAS e 2 pacientes no grupo rivaroxabana; p= 1,0), e outros 4 pacientes, no 14° dia do pós-operatório (1 paciente no grupo AAS e 3 pacientes no grupo rivaroxabana; p= 0,292). Nenhum paciente da amostra apresentou hematoma da ferida cirúrgica, sangramento de órgão importante, infecção da ferida, ou necessidade de nova cirurgia. Conclusão A aspirina e a rivaroxabana apresentaram eficácia comparável na prevenção do TEV, sem aumentar a incidência de complicações da ferida e sangramento após ATJ.

Treatment and secondary prophylaxis of venous thromboembolism in cancer patients.

Cancer-associated thrombosis (CAT) adversely affects the quality of life and survival of people with cancer. A holistic approach is optimal for the treatment and secondary prophylaxis of venous thromboembolism (VTE) including shared decision-making around anticoagulation, considering individual risk factors for VTE recurrence, morbidities from VTE, and resources available in cancer centres around the world. Taking a global perspective on availability and cost, this paper guides the reader through the wider aspects of treatment and secondary thromboprophylaxis which, in turn, influence the recent international guidelines.

Effectiveness and Safety of Extended Oral Anticoagulant Therapy in Patients with Venous Thromboembolism: A Retrospective Cohort Study.

Limited real-world evidence exists for effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment in prevention of recurrent venous thromboembolism (VTE) and adverse major bleeding events among patients with VTE. Using MarketScan Commercial and Medicare Supplemental databases (2013-2019), we conducted a retrospective cohort study to compare the risk of recurrent VTE and major bleeding events during extended treatment among patients with VTE who completed the 6-month initial treatment and received extended oral anticoagulant treatment with apixaban, warfarin, or no extended treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards modeling with inverse probability treatment weighting. We identified 14,818 patients with extended treatment of apixaban (n = 4,338), warfarin (n = 5,298), or no extended treatment (n = 5,182). Compared with no extended treatment, apixaban use was associated with decreased risk of recurrent VTE (HR: 0.10, 95% CI: 0.04-0.26) without increased risk of major bleeding events (HR: 1.06, 95% CI: 0.52-2.17); warfarin use was associated with decreased risk of recurrent VTE (HR: 0.23, 95% CI: 0.12-0.44) but with increased risk of major bleeding events (HR: 2.64, 95% CI: 1.51-4.59). Compared with warfarin, apixaban use was associated with decreased risk of major bleeding events (HR: 0.42, 95% CI: 0.22-0.80) but no difference in risk of recurrent VTE (HR: 0.46, 95% CI: 0.15-1.36). In a real-world clinical setting, extended anticoagulation with apixaban or warfarin was associated with decreased risk of recurrent VTE compared with no extended treatment, and apixaban had a better safety profile with fewer major bleeding events compared with warfarin among commercially insured patients with VTE.

A Single-Center, Randomized, Double-Blind Study of 94 Patients Undergoing Surgery for Cerebral Glioma to Compare Postoperative Thromboprophylaxis with and without Rivaroxaban.

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Editor's Choice - Severe Bleeding Risks of Direct Oral Anticoagulants in the Prevention and Treatment of Venous Thromboembolism: A Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6). CONCLUSIONS: For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

Statins for venous event reduction in patients with venous thromboembolism: A multicenter randomized controlled pilot trial assessing feasibility.

BACKGROUND: Statins may reduce the risk for recurrent venous thromboembolism (VTE); however, no randomized trials have explored this hypothesis. We performed a pilot randomized trial to determine feasibility of recruitment for a larger trial of secondary VTE prevention with rosuvastatin. METHODS: Patients with a newly diagnosed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, receiving standard anticoagulation, were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days or no rosuvastatin for 6 months. RESULTS: Between November 2016 and December 2019, 3391 patients were assessed for eligibility in six centers. Of these patients, 1347 (39.7%) were eligible and approached for participation in the trial and 312 (23.1%) were randomized. The mean rate of randomization was 8.2 ± 4.3 patients per month. During follow-up, five recurrent VTE events were observed, three (1.9%) in the rosuvastatin group (two pulmonary embolism, one deep vein thrombosis), and two (1.3%) in the control group (two pulmonary embolism; P = 0.68). One major arterial event occurred in the rosuvastatin arm and none in the control arm (0.6% vs. 0%, P = 0.50). CONCLUSION: This pilot trial supports the feasibility of a larger scale randomized controlled trial to determine the efficacy of adjuvant rosuvastatin for the secondary prevention of VTE.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (ß = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Recurrent Thrombi in an Obese Patient With History of Bariatric Surgery Despite Anti-Xa Therapy.

Obesity and gastric bypass surgery can complicate anticoagulation therapy. In general, patients post-bariatric surgery are considered to be at a moderate risk for deep venous thromboembolism or pulmonary embolism. American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists guidelines recommend chemical prophylaxis with unfractionated heparin or low molecular weight heparin after surgery until the patient is fully mobile, and for those who require chronic anticoagulation, the International Society of Thrombosis and Haemostasis recommend warfarin if body mass index (BMI) is above 40 kg/m2 or weight is more than 120 kg. Clinical decision making regarding anticoagulation in the following patient case is complicated by multiple factors, most notably the combination of obesity and history of gastric bypass surgery. This patient failed multiple anticoagulation regimens, with apixaban and rivaroxaban therapies each ending in venous thromboemboli and warfarin leading to subtherapeutic International Normalized Ratio (INR)s despite dose adjustment. However, she is currently therapeutic on the combination of enoxaparin and warfarin as shown by INR and anti-Xa level monitoring. In this case and similar instances, there could be a need for anticoagulant dose adjustments, different INR goals, or a combination of different anticoagulants. Providers should take an individualized approach to patients who have had bariatric surgery with elevated BMI as a key factor in anticoagulant selection.