Venous Thromboembolism Risk and Adherence to Pharmacological Thromboprophylaxis in Hospitalized Patients in Uruguay: First Nationwide Study.

INTRODUCTION: Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels. AIM: To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay. METHODS: An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients. RESULTS: 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were "protected" against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk. CONCLUSIONS: Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay.

Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Improving Compliance with a Nurse-Driven Protocol for Unfractionated Heparin Infusions in Patients with Venous Thromboembolism.

BACKGROUND: Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE). PURPOSE: The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol. METHODS: Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance. INTERVENTIONS: Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol. RESULTS: The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period. CONCLUSIONS: A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT.

Anticoagulation stewardship: Improving adherence to clinical guidelines and reducing overuse of venous thromboembolism prophylaxis in hospitalized medical patients.

Adherence to guideline recommendations for venous thromboembolism prophylaxis (VTE) in hospitalized medical patients is suboptimal despite national policies and institutional interventions. The aim of this quality improvement project was to improve adherence to guidelines and decrease the overuse of VTE prophylaxis in order to reduce the institutional cost for heparins. A multidisciplinary anticoagulation stewardship program (ACSP) using the audit and feedback strategy was implemented on the medicine inpatient units at a teaching hospital in Canada. The primary outcome measure was a comparison, pre and post introduction of the ACSP, of the costs per 6-month period for prophylactic dose enoxaparin and unfractionated heparin on the medicine units. The balancing measures were the 90-day VTE rate and major bleeding rate during the hospitalization. Six months after the implementation of the ACSP, the cost was decreased by >50 % without any observed negative impact on patient safety. This study demonstrates the potential for anticoagulation stewardship programs to optimize the use of VTE prophylaxis and reduce the associated costs and risks.

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism.

INTRODUCTION: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. METHODS: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. RESULTS: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. CONCLUSIONS: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Management options for pediatric venous thromboembolic disease: Beyond anticoagulation with endovascular therapies.

Venous thromboembolism (VTE) in pediatric patients is an uncommon but serious diagnosis that has an array of therapeutic options and challenges. An assessment of the existing literature on management of pediatric patients with VTE was conducted. The interventions reviewed include anticoagulation, thrombolysis, thrombectomy, inferior vena cava (IVC) filters, and venous stenting. For each intervention, a discussion of mechanism of action, indications, contraindications, and potential complications was performed. While anticoagulants are considered the first-line pediatric VTE treatment, many drugs remain investigational in this patient population and treatment recommendations are extrapolated from adult practice. Thrombolysis may be indicated in cases of acute thrombosis requiring more rapid clot resolution but presents a greater bleeding risk than anticoagulation. Similarly, thrombectomy also provides rapid clot resolution and offers a larger therapeutic window and usage in more mature thrombi than thrombolysis. In select patient groups, IVC filters may be indicated in the prevention of PE but present with inherent thrombogenicity and risk of migration. The data regarding pediatric VTE treatment options, monitoring, and long term outcomes is limited compared to the adult population. The relatively few clinical trials including pediatric patients have a relatively small sample size and are heterogenous with regards to predisposing factors that further exacerbate generalizability. Additional research is needed to help construct and evaluate a robust treatment algorithm for pediatric patients with VTE.

[Translation into French and republication of: "Recurrent venous thromboembolism in anticoagulated cancer patients: diagnosis and treatment"]. / Traduction et republication de : « Maladie thromboembolique veineuse récidivante chez les patients cancéreux anticoagulés : diagnostic et traitement ¼.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

Management of lower-extremity venous thromboembolism: An updated review.

According to the 2021 updated guidelines of the American College of Chest Physicians, the location of venous thromboembolism, the severity of symptoms, the risk of thrombus extension vs that of bleeding, and comorbidities all affect the decision to treat, the choice of anti-thrombotic agent, and the duration of therapy. In patients with isolated distal deep vein thrombosis without high-risk features, monitoring progression is recommended over initiating anticoagulation. However, treatment of proximal deep vein thrombosis with anticoagulation is strongly recommended by the guidelines. More evidence now supports the treatment of superficial vein thrombosis with anticoagulation in high-risk patients.

Anti-Xa Monitoring of Apixaban (ZyQuis) in Venous Thrombo-Embolism and Atrial Fibrillation.

Apixaban is a direct oral Xa inhibitor and is indicated for the treatment of venous thrombo-embolism (VTE) and prevention of stroke in atrial fibrillation (AF). Recently, a generic (ZyQuis, Zydus Lifesciences Limited, India) has received Food and Drug Administration approval. While bioequivalence has been demonstrated with Eliquis (Bristol-Myers Squibb/Pfizer, UK), it is necessary to monitor its effectiveness prior to acceptance in medical practice. This prospective study independently evaluated Apixaban (ZyQuis) at two accredited laboratories. Participants were converted from Warfarin or Rivaroxaban to Apixaban 5 mg bd for a duration of one month. Peak anti-Xa levels were measured 3-4 h post the morning dose. The samples were processed on the Atellica COAG 360 (Siemens Healthineers, Marburg, Germany) analyzers with a chromogenic anti-Xa assay (Innovance, reference interval 69-321 ng/mL). There were 26 participants; 5 men, 21 women; mean ± standard deviation age of 46 ± 12 years. Indications for anticoagulation included: VTE (88.5%) and AF (11.5%). 69.2% of the participants had at least one comorbidity. 96.2% of the anti-Xa levels were within the laboratory's 95% reference interval. Mean anti-Xa activity was 191 ± 69 ng/mL and 186 ± 68 ng/mL measured at respective laboratories. Mean differences in anti-Xa measurements represented by Bland-Altman statistics were small (bias of -2.6%, 95% confidence interval -1.11 to -4.09) and a strong correlation was observed on Deming regression analysis (0.995). Apixaban (ZyQuis) was effective for the management of VTE and AF as evidenced by anti-Xa activity.

Aspirin or enoxaparin for VTE prophylaxis after primary partial, total or revision hip or knee arthroplasty: A secondary analysis from the CRISTAL cluster randomized trial.

BACKGROUND: This study compares aspirin to enoxaparin for symptomatic VTE prophylaxis within 90 days of any type of hip or knee arthroplasty performed for any diagnosis, in patients enrolled in the CRISTAL trial. MATERIALS AND METHODS: CRISTAL was a cluster-randomised crossover, registry-nested non-inferiority trial across 31 hospitals in Australia. The primary publication was restricted to patients undergoing primary total hip or knee arthroplasty for a diagnosis of osteoarthritis. This report includes all enrolled patients undergoing hip or knee arthroplasty procedures (partial or total, primary or revision) performed for any indication. Hospitals were randomized to administer patients aspirin (100mg daily) or enoxaparin (40mg daily), for 35 days after hip arthroplasty and 14 days after knee arthroplasty. Crossover occurred after the patient enrolment target had been met for the first group. The primary outcome was symptomatic VTE within 90 days. Analyses were performed by randomization group. RESULTS: Between April 20, 2019 and December 18, 2020, 12384 patients were enrolled (7238 aspirin group and 5146 enoxaparin). Of these, 6901 (95.3%) given aspirin and 4827 (93.8%) given enoxaparin (total 11728, 94.7%) were included in the final analyses. Within 90 days, symptomatic VTE occurred in 226 (3.27%) aspirin patients and 85 (1.76%) enoxaparin patients, significant for the superiority of enoxaparin (estimated treatment difference 1.85%, 95% CI 0.59% to 3.10%, p = 0.004). Joint-related reoperation within 90 days was lower in the enoxaparin group (109/4827 (2.26%) vs 171/6896 (2.47%) with aspirin, estimated difference 0.77%; 95% CI 0.06% to 1.47%, p = 0.03). There were no significant differences in the other secondary outcomes. CONCLUSION: In patients undergoing hip or knee arthroplasty (of any type, performed for any indication) enrolled in the CRISTAL trial, aspirin compared to enoxaparin resulted in a significantly higher rate of symptomatic VTE and joint-related reoperation within 90 days. These findings extend the applicability of the CRISTAL trial results. TRIAL REGISTRATION: Anzctr.org.au, identifier: ACTRN12618001879257.

International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Potential treatment option of rivaroxaban for breastfeeding women: A case series.

The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients.

Recurrent Venous Thromboembolism in Patients on Anticoagulation: An Update Based on the Revised AWMF S2k Guideline.

In the recently updated German S2k Guideline "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism," a new chapter was incorporated about recurrent venous thromboembolism (VTE) in patients on anticoagulation treatment. Despite the high efficacy of anticoagulation in most patients, approximately 2% experience a recurrent VTE event while receiving anticoagulant drugs. The proper diagnosis of the recurrent VTE is important and possible only with the knowledge of localization and thrombus burden of the primary VTE event. Possible reasons for recurrent VTE events in patients on anticoagulation are non-adherence to medication, sub-therapeutic drug levels due to resorption disorders or drug interactions, or concomitant disease with high thrombogenicity. Cancer is the most common underlying disease, but it is important to investigate and understand possible other causes whenever a breakthrough VTE event occurs. This results in the recommendation that in patients with VTE recurrence on therapeutic anticoagulation, in particular, the presence of malignant disease, antiphospholipid syndrome, and rare diseases like paroxysmal nocturnal hemoglobinuria or Behçet's disease should be considered. For VTE recurrence during heparin therapy, heparin-induced thrombocytopenia type II needs to be ruled out, even if platelet counts are within the normal range. Although the mechanisms of recurrence on anticoagulation can be evaluated in a certain degree, clinical evidence for the management of recurrent VTE in anticoagulated patients is minimal and mainly based on expert opinion. Switching anticoagulant medication and intensifying anticoagulant treatment are possible options.

Oral anticoagulant therapy in older adults.

Patients aged ≥65 years not only account for the majority of patients with atrial fibrillation (AF) and venous thromboembolism (VTE), they are also at a higher risk of morbidity, mortality, and undertreatment than younger patients. Several age-related physiological changes with effects on drug pharmacokinetics/-dynamics and blood vessel fragility as well as the higher prevalence of geriatric conditions such as frailty, multimorbidity, polypharmacy, fall risk, dementia, and malnutrition make older persons more vulnerable to disease- and anticoagulation-related complications. Moreover, because older patients with AF/VTE are underrepresented in oral anticoagulation (OAC) trials, evidence on OAC in older adults with AF/VTE is mainly based on subgroup analyses from clinical trials and observational studies. A growing body of such limited evidence suggests that direct oral anticoagulants (DOACs) may be superior in terms of efficacy and safety compared to vitamin K antagonists in older persons with AF/VTE and that specific DOACs may have a differing risk-benefit profile. In this narrative review, we summarize the evidence on epidemiology of AF/VTE, impact of age-related physiological changes, efficacy/safety of OAC, specifically considering individuals with common geriatric conditions, and review OAC guideline recommendations for older adults with AF/VTE. We also propose a research agenda to improve the evidence basis on OAC older individuals with AF/VTE, including the conduct of advanced age-specific and pragmatic studies using less restrictive eligibility criteria and patient-reported health outcomes, in order to compare the effectiveness and safety of different DOACs, and investigate lower-dose regimens and optimal OAC durations in older patients.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

D-dimer and risk of venous thromboembolism recurrence: Comparison of two studies with similar designs but different laboratory and clinical results.

BACKGROUND: D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results. METHODS: Both studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results. RESULTS: More D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive D-dimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9). CONCLUSION: The low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.