Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry.

INTRODUCTION: Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event. METHODS: Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation. RESULTS: Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44-3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5-4.45). CONCLUSION: Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

The prognostic value of blood cellular indices in pulmonary embolism.

Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism.

BACKGROUND: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. OBJECTIVES: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. METHODS: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. RESULTS: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. CONCLUSION: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Venous Thromboembolism Characteristics and Outcomes Among RIETE Patients Tested & Untested for Inherited Thrombophilia.

Inherited thrombophilia (IT) workup is commonly pursued in venous thromboembolism (VTE) patients. Recent American Society of Hematology (ASH) guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large prospective RIETE registry was analyzed to compare VTE risk factors, management and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and following its discontinuation. Among 103,818 patients enrolled in RIETE, 21,089 (20.3%) were tested for IT, 8,422 (8.1%) tested positive, and 82,729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors, and less common in those with major risk factors like surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However IT-negative patients with pregnancy or postpartum-related VTE, had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates post-treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities.

Venous thromboembolism (VTE) developing after ankle sprain. Comparison with VTE after knee arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) is a critical complication after non-major trauma or surgery. While the risk and severity of VTE following major orthopedic surgery is well-documented, there is significant knowledge gap regarding, non-major trauma such as ankle sprains. METHODS: We analyzed data from the RIETE registry to assess the clinical characteristics, VTE prophylaxis usage, and outcomes in patients with VTE following ankle sprain versus those post elective knee arthroplasty. We aimed to assess the risk and severity of VTE in a population traditionally considered at lower risk. Risk stratification was performed using the TRiP(cast) score. RESULTS: Among 1,250 patients with VTE, those with ankle sprain (n = 459) were much younger than those post knee arthroplasty (n = 791), less often female, had fewer comorbidities, and received VTE prophylaxis less often (27% vs. 93 %). During anticoagulation, 26 patients developed recurrent VTE, 31 had major bleeding, and 12 died (fatal PE 3, fatal bleeding 2). There were no differences between the two groups in the rates of VTE recurrences (rate ratio (RR): 1.65; 95%CI: 0.69-3.88) or death (RR: 1.12; 95%CI: 0.33-3.46), but patients with VTE after ankle sprain had a lower rate of major bleeding (RR: 0.39; 95%CI: 0.13-0.99). CONCLUSIONS: Ankle sprain patients are often undertreated for VTE prophylaxis and have similar severity of VTE than those undergoing elective knee surgery, indicating the need for a more customized approach to VTE management.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry / Diferencias relacionadas con la edad en la presentación, el tratamiento y los resultados clínicos de 100.000 pacientes con tromboembolismo venoso en el registro RIETE

Introduction: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. Methods: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. Results: From January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22–1.52) and major bleeding (OR, 2.08; 95%CI, 1.85–2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54–0.71). Conclusions: Compared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.(AU)

Outcomes of venous thromboembolism in patients with inherited thrombophilia treated with direct oral anticoagulants: insights from the RIETE registry.

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. RESULTS: From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69-0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72-0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32-0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50-0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60-0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59-0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27-0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

External validation of the PE-SARD risk score for predicting early bleeding in acute pulmonary embolism in the RIETE Registry.

INTRODUCTION: The PE-SARD score (syncope, anemia, renal dysfunction) was developed to predict the risk of major bleeding in the acute phase of pulmonary embolism (PE). METHODS: We analyzed data from 50,686 patients with acute PE included in the RIETE registry to externally validate the PE-SARD score. We calculated the overall reliability of the PE-SARD score, as well as discrimination and calibration for predicting the risk of major bleeding at 30 days. The performance of PE-SARD was compared to the BACS and PE-CH models. RESULTS: During the first 30 days, 640 patients (1.3 %) had a major bleeding event. The incidence of major bleeding within 30 days was 0.6 % in the PE-SARD-defined low-risk group, 1.5 % in the intermediate-risk group, and 2.5 % in the high-risk group, for an OR of 2.22 (95 % CI, 2.02-2.43) for the intermediate-risk group (vs low-risk group), and 3.94 for the high-risk group (vs low-risk group). The corresponding sensitivity was 81.1 % (intermediate/high vs low risk), and specificity was 85.9 % (95 % CI, 85.8-86.1) (low/intermediate vs high risk). The applicability of PE-SARD was consistent across clinically relevant patient subgroups and over shorter time periods of follow-up (i.e., 3 and 7 days). The C-index was 0.654 and calibration was excellent. The PE-SARD bleeding score improved the major bleeding risk prediction compared with the BACS and PE-CH scores. CONCLUSIONS: The PE-SARD score identifies PE patients with a higher risk of bleeding, which could assist providers for potentially adjusting PE management, in a framework of shared decision-making with individual patients.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry.

INTRODUCTION: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. METHODS: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. RESULTS: From January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22-1.52) and major bleeding (OR, 2.08; 95%CI, 1.85-2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54-0.71). CONCLUSIONS: Compared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Validation of Echocardiographic Measurements in Patients with Pulmonary Embolism in the RIETE Registry.

Background In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis.

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT. RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

Real life results of direct-acting oral anticoagulants recommended-dose in obese vs normal-weight patients with venous thromboembolism.

BACKGROUND: There is scarce evidence on the effectiveness and safety of recommended-dose direct acting oral anticoagulants (DOACs) in obese patients with venous thromboembolism (VTE). MATERIAL AND METHODS: We used the data in the RIETE registry to compare the rates of VTE recurrences and major bleeding during long-term therapy with DOACs at recommended doses in patients with body mass index ≥30 kg/m2 (obese) vs. those with BMI 18.5-24.9 kg/m2 (normal weight). We performed regression models with competing risks for death. RESULTS: From January 2013 through October 2022, 2885 obese patients and 2676 with normal weight in RIETE received rivaroxaban (n = 3020), apixaban (n = 1754), edoxaban (n = 636) or dabigatran (n = 151). Median age was 63 years and 52 % were female. At baseline, obese patients were more likely to have diabetes (18.6 % vs. 8.4 %), hypertension (51.9 % vs. 31.4 %) or pulmonary embolism (67.7 % vs. 61 %), and less likely to have renal insufficiency (5.3 % vs. 16 %) or anaemia (21.8 % vs. 28 %%). During anticoagulation (median, 147 vs. 101 days), the obese had a similar rate of VTE recurrences (1.71 vs. 2.14 events per 100 patients-years; hazard ratio (HR): 0.81; 95 % CI: 0.49-1.34) or major bleeding (1.45 vs. 1.76 per 100 patients-years; HR: 0.91; 95 % CI: 0.52-1.59) than those with normal weight. These findings persisted after multivariable analysis (recurrent VTE, HR: 0.80; 95 % CI: 0.48-1.32; major bleeding, HR: 1.11; 95 % CI: 0.60-2.07). CONCLUSION: The use of DOACs at recommended doses in obese patients with VTE was associated with similar rates of VTE recurrences or major bleeding than in patients with normal weight.