Risk Of Recurrent Venous Thromboembolism Research Articles

Subsegmental Pulmonary Embolism.

Subsegmental pulmonary embolism (SSPE) is increasingly diagnosed with the growing use and technological advancements of multidetector computed tomography pulmonary angiography. Its diagnosis is challenging, and some presumed SSPE may actually represent imaging artifacts. Indirect evidence and results from small observational studies suggest that SSPE may be more benign than more proximal pulmonary embolism, and may thus not always require treatment. Therefore, guidelines suggest to consider a management strategy without anticoagulation in selected patients with SSPE at low risk of recurrent venous thromboembolism (VTE), in whom proximal deep vein thrombosis is excluded. Recently, a large prospective study among low-risk patients with SSPE who were left untreated showed a higher VTE recurrence risk than initially deemed acceptable by the investigators, and thus was prematurely interrupted after recruitment of 97% of the target population. However, the risk-benefit ratio of anticoagulation for low-risk patients with SSPE remains unclear, and results from randomized trials are needed to answer the question about their optimal management.

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis.

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, albeit with no statistical difference. Statistical significance was observed for no major clinically relevant bleeding but not for major bleeding.

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study

BackgroundClinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking. ObjectivesWe aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment. Patients/MethodsConsecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3–6 months. PTS was diagnosed using the Villalta score after 6–24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study. ResultsIn total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15–2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14–9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04–4.58]). ConclusionsPatients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.

Intensify Standardized Anticoagulation for Cancer-associated Pulmonary Embolism: From Single-center Real-world Data

Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE. A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding). Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P=0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P=0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P=0.001). The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies

BackgroundA main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. MethodsTo quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. ResultsAmong 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3–11.9) for recurrent VTE and 6.7 % (95 % CI 4.2–10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. ConclusionsThere are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

PB0486 Effect of Age on Risk for Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis

PB0486 Effect of Age on Risk for Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis

The Vienna Prediction Model for identifying patients at low risk of recurrent venous thromboembolism: a prospective cohort study.

Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients. In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years. A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM's baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE. In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.

Serial D-dimers after anticoagulant cessation in unprovoked venous thromboembolism: Data from the REVERSE cohort study

IntroductionWhile several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation. MethodsUsing the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles. ResultsAmong 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9–2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1–2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4–5.6) among patients in the lowest ∆D-dimer quartile. ConclusionSerial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.

Thrombin Generation Is Associated with Venous Thromboembolism Recurrence, but Not with Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study.

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12-14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28-3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis

The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Erasmus MC.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Obesity.

Background: Direct oral anticoagulants (DOACs) are known to have similar efficacy with a decreased risk of bleeding when compared to warfarin for the treatment of venous thromboembolism (VTE). In patients with obesity, there are limited data regarding the safety and efficacy of DOACs. Despite concerns for both under- and over-dosing patients with extremes of body weight, there are no dose adjustment recommendations in the package inserts for any of the DOACs. Objective: To evaluate the safety and efficacy of DOACs versus warfarin for the treatment of VTE in patients with obesity. Methods: This single-center, retrospective cohort study included obese patients initiated on DOAC or warfarin therapy for VTE from January 2015 to January 2022. Patients with cancer, hypercoagulable disorders, end-stage kidney disease, or pregnancy were excluded. The primary endpoint was VTE recurrence. Secondary endpoints included major and minor bleeding. Results: A total of 120 patients met criteria for inclusion. Ninety-two received DOAC therapy and 28 received warfarin. The primary endpoint occurred in 4 patients in the DOAC group and 3 patients in the warfarin group (P = 0.35). Major bleeding occurred in 2 patients. Minor bleeding events occurred in 10 (8.33%) patients. Of those, 6 (6.5%) events occurred in patients receiving a DOAC and 4 (14.3%) events occurred in patients receiving warfarin (P = 0.28). Limitations of this study include the retrospective single-center study design. Conclusions: There was a comparable risk of bleeding and recurrent VTE between DOACs and warfarin in patients initiated on therapy for VTE.

Risk of recurrent cancer-associated venous thromboembolism: A Danish nationwide cohort study

BackgroundPredictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. MethodsUsing Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003–2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. ResultsThe population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). ConclusionsSix-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism.

Clinical Outcomes of Direct Oral Anticoagulants vs Warfarin for Extended Treatment of Venous Thromboembolism

Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin. To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE. This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023. Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE. The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression. A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment. In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.

Comparative Efficacy of Oral Apixaban and Subcutaneous Low Molecular Weight Heparins in the Treatment of Cancer-Associated Thromboembolism: A Meta-Analysis.

Cancer patients' risk of developing venous thromboembolism (VTE) is four to seven times higher than the general population. Cancer-associated VTE (CA-VTE), is a leading cause of morbidity and mortality in cancer patients. Low Molecular Weight Heparin (LMWH) has historically been the mainstay treatment ofCA-VTE; however, complications such as bleeding and recurrent VTE make it challenging to manage these patients. Recent randomized controlled trials (RCTs) have proven that direct oral anticoagulants (DOACs) are as efficacious as LMWHs in treating CA-VTE. We conducted a systematic review and meta-analysis to ascertain the efficacy and safety of LMWH and Apixaban for the treatment of CA-VTE.A systematic review was conducted using Medline, Embase, and Scopus, databases for all cohort studies, case-control studies, and RCTs in English comparing cancer patients undergoing treatment with Apixaban or LMWH to treat CA-VTE from inception-May 2023. The Review Manager program, version 5.4.1, was used for statistical analysis and the Mantel-Haenszel fixed-effects models to calculate the risk ratio (RR) and 95% confidence intervals (CIs) and the inverse variance approach to get the weighted mean difference for the continuous outcomes. Q-test for heterogeneity was used to examine statistical heterogeneity and an I2 statistics value >50%was defined as significant heterogeneity. A total of four studies were included, and the total number of patients was 1,632 across all studies. The Apixaban group was associated with a statistically significant increase in minor bleeding (RR 1.57; 95% CI (1.12, 2.21); p=0.009; I2=0%), but not for major and total bleeding. The Apixaban group showed a statistically significant lower risk of recurrent VTE when compared to the LMWH group (RR: 0.61; 95% CI (0.41, 0.92); p=0.02; I2 = 7%), and there was no statistically significant difference in terms of mortality between the two groups (RR: 0.89;95% CI (0.73, 1.09); I2=0). Our findings suggest that Apixaban may be a favorable anticoagulant option for managing cancer-associated thromboembolism, as it demonstrated a lower risk of recurrent VTE. The risk of bleeding with DOAC in gastrointestinal cancers warrants further investigation.

Prevalence of and Eligibility for Surveillance Without Anticoagulation Among Adults With Lower-Risk Acute Subsegmental Pulmonary Embolism

Approximately 8% of acute pulmonary emboli are confined to the subsegmental arteries. The 2016 and 2021 American College of Chest Physicians (CHEST) guidelines and expert panel reports suggest the use of structured surveillance without anticoagulation for select ambulatory patients with subsegmental pulmonary embolism who do not have active cancer, deep vein thrombosis, impaired cardiopulmonary reserve, marked symptoms, or increased risk of recurrent venous thromboembolism; however, guideline uptake in community practice is unknown, as is the proportion of outpatients eligible for surveillance. To describe the prevalence of surveillance among outpatients with acute subsegmental pulmonary embolism and to estimate the proportion of patients eligible for structured surveillance using modified CHEST criteria. This retrospective cohort study was conducted across 21 US community hospitals in the Kaiser Permanente Northern California integrated health system from January 1, 2017, to December 31, 2021. Adult outpatients with acute subsegmental pulmonary embolism were included. Patients with the following higher-risk characteristics were excluded: codiagnoses requiring hospitalization, non-low-risk vital signs (ie, systolic blood pressure <90 mm Hg, pulse ≥110 bpm, or peripheral cutaneous pulse oximetry ≤92%), prediagnosis anticoagulant use, or hospice care. Data analysis was performed from November 2022 to February 2023. The main outcomes were the (1) prevalence of surveillance and (2) eligibility for surveillance using 2 sets of criteria: the CHEST criteria modified by excluding patients with higher-risk characteristics or right ventricular dysfunction and a stricter set of criteria requiring age younger than 65 years and no more than 1 embolus. The prevalence of structured surveillance was calculated and the proportion of patients eligible for surveillance was estimated. Of the 666 outpatients with acute subsegmental pulmonary embolism included in this study, 229 with lower-risk characteristics were examined. Their median age was 58 (IQR, 42-68) years; more than half were men (120 [52.4%]) and self-identified as non-Hispanic White (128 [55.9%]). Six patients (2.6%) were initially not treated with anticoagulants. Among the lower-risk cohort, only 1 patient (0.4% [95% CI, 0.01%-2.4%]) underwent structured surveillance, without 90-day sequelae. Thirty-five patients (15.3% of the lower-risk group and 5.3% of the full cohort) were surveillance eligible using modified CHEST criteria. Fifteen patients (6.6% of the lower-risk group and 2.3% of the full cohort) were surveillance eligible using stricter criteria. In this cohort study of lower-risk outpatients with subsegmental pulmonary embolism, few were eligible for structured surveillance, and only a small proportion of eligible patients underwent surveillance despite the CHEST guideline. If forthcoming trials find surveillance safe and effective, substantial uptake into clinical practice may require more than passive diffusion.

Acute venous thromboembolism in patients with brain cancer: clinical course

BackgroundPatients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). ObjectivesThe aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. MethodsThis was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. ResultsOverall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. ConclusionIn patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study

Serum uric acid (SUA) levels have been associated with an increased risk and recurrence of venous thromboembolism (VTE) in European populations, but the potential causal relationship remains unclear. Large-scale studies on the association between SUA and VTE in East Asian populations are lacking, despite the high prevalence of hyperuricemia in this region. To address this, we conducted a cohort analysis and a two-sample Mendelian randomization (MR) study in East Asian populations. We collected data on VTE patients from the China Pulmonary Thromboembolism Registry Study (CURES) and compared them to controls obtained from the China Health and Retirement Longitudinal Survey (CHARLS). Propensity score matching (PSM) and cubic-spline models were applied to assess the effect of SUA on VTE risk while adjusting for multiple covariates. We also performed two-sample MR analyses to infer potential causality based on summary statistics from Genome-wide Association Studies (GWAS) of SUA and VTE in the East Asian population. We found that the SUA levels were higher in VTE patients (317.95mmol/L) compared to the general population (295.75mmol/L), and SUA ≥ 325mmol/L was associated with an increased risk of VTE recurrence (P-value=0.0001). The univariable MR suggested a causal relationship between elevated SUA and higher VTE risk (Pinverse variance weighted < 0.05), and multivariable MR showed that elevated SUA levels continued to promote the development of VTE after adjusting for multiple covariates (Pmultivariable residual < 0.05). Sensitivity analyses produced similar results for these estimations. Our study provides evidence supporting a robust positive association between SUA and VTE in the East Asian population, and MR analyses suggest that this association is likely to be causal. Our findings underscore the importance of monitoring SUA levels in VTE prevention and call for urgent action to address the growing burden of hyperuricemia in the Asia-Pacific region. This research was funded by Beijing Nova Program (No. Z211100002121057), National Natural Science Foundation of China (No. 82100065 and No. 62350004), CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-061 and No. 2021-1-I2M-001), Elite Medical Professionals project of China-Japan Friendship Hospital (No. ZRJY2021-QM12), National Key Research and Development Project (No. 2021YFF1201200 and No. 2022YFC3341004).

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis

Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored. To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting. This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021. The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin. Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs. This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs. In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis

ObjectiveIsolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. MethodsConsecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. ResultsA total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). ConclusionsStandard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Safety and efficacy of apixaban versus low-molecular weight heparin or vitamin-K antagonists for venous thromboembolism treatment in patients with severe renal failure: A systematic review and meta-analysis

IntroductionChronic kidney disease is an independent risk factor for venous thromboembolism (VTE). Traditionally, Low Molecular Weight Heparin (LMWH) followed by warfarin has been the conventional therapy for VTE treatment. Direct oral anticoagulants (DOACs), including apixaban, have shown several advantages over the traditional therapy in individuals with normal kidney function. This meta-analysis aims to review the safety and efficacy of apixaban compared to warfarin or LMWH for the treatment of VTE in severe renal failure. MethodWe conducted literature search in PubMed, Embase, and Cochrane databases. Retrospective observational studies involving clinical effectiveness and safety outcomes of apixaban compared to warfarin in adult patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/m2 or on dialysis were included. ResultsEight studies were included in the analysis. Significant reduction in VTE recurrence observed in apixaban compared to warfarin (RR, 0.65; 95 % CI, 0.43–0.98; P = 0.04; I2 = 78 %). No significant difference in all-cause mortality between apixaban and warfarin (RR, 0.99; 95 % CI, 0.91–1.07; P = 0.74; I2 = 0 %). Apixaban showed a significantly lower rate of major bleeding (RR, 0.72; 95 % CI, 0.62–0.84; P < 0.0001; I2 = 34 %) and minor bleeding events (RR, 0.42; 95 % CI, 0.21–0.86; P = 0.02; I2 = 10 %) compared to warfarin. No significant difference observed in clinically relevant non-major bleeding between apixaban and warfarin (RR, 0.81; 95 % CI, 0.65–1.00; P = 0.05; I2 = 67 %). ConclusionApixaban was favored over warfarin for treating VTE in severe renal failure, reducing VTE recurrence and bleeding risk. No differences were observed in all-cause mortality and CRNMB events. More evidence is required due to limited RCTs and prospective studies.