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.

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry.

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Deep vein thrombosis symptoms and 30-day mortality in acute pulmonary embolism.

BACKGROUND: In patients with acute symptomatic pulmonary embolism (PE), the presence of concomitant lower-limb deep vein thrombosis (DVT) has been associated with a higher mortality rate. The prognostic significance of DVT symptoms among these patients remains uncertain. METHODS: We used the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 30-day mortality rate in patients with PE and concomitant lower-limb DVT, according to the presence or absence of DVT symptoms. Primary outcomes were all-cause death and PE-related death within the first 30 days. RESULTS: Since March 2001 to June 2021, there were 17,742 patients with acute symptomatic PE and objectively proven concomitant lower-limb DVT. Of these, 11,984 (68%) had DVT symptoms. Most patients with or without DVT symptoms (82% vs. 81%) received low-molecular-weight heparin initially. Then, most (61% vs. 58%) switched to vitamin K antagonists. During the first 30 days of therapy, 497 patients with DVT symptoms (4.1%) and 164 (2.8%) with no DVT symptoms died (rate ratio [RR]: 1.48; 95%CI: 1.23-1.77). The rates of PE-related death were: 1.0% vs. 0.7%, respectively (RR: 1.50; 95%CI: 1.04-2.16). On multivariable analysis, patients with DVT symptoms were at increased risk for all-cause death (adjusted hazard ratio [aHR]: 1.49; 95%CI: 1.24-1.78), and PE-related death (aHR: 1.52; 95%CI: 1.05-2.20). CONCLUSION: Among patients with acute symptomatic PE and concomitant lower-limb DVT, those with DVT symptoms had an increased all-cause and PE-related mortality within 30 days. Assessment of DVT symptoms would assist with risk stratification of these patients.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

A RIETE registry analysis of patients with upper extremity deep vein thrombosis and thoracic outlet syndrome.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) related to thoracic outlet syndrome (TOS) is rare, and the literature is limited to institutional case series. METHODS: We used data from the RIETE Registry to compare outcomes (recurrences, major bleeding and signs and symptoms of post-thrombotic [PTS] syndrome) in patients with UEDVT and TOS undergoing first rib resection vs. those not undergoing surgery. RESULTS: From March 2001 to March 2021, there were 4214 patients with UEDVT, of whom 209 (4.96%) had TOS. Of these, 55 (26%) underwent first rib resection. Patients with TOS were younger and less likely to have comorbidities than those without TOS. There were no differences between patients with TOS undergoing surgery and those who did not. During anticoagulation, patients with TOS had a non-statistically significant lower rate of VTE recurrences than those without TOS (hazard ratio [HR]: 0.46; 95%CI: 0.14-1.12) and a lower bleeding rate (HR: 0.16; 95%CI: 0.01-0.83). No patient with TOS developed pulmonary embolism or died. Patients with TOS undergoing surgery had fewer PTS symptoms (odds ratio [OR]: 0.21; 95%CI: 0.06-0.68) or signs (OR: 0.11; 95%CI: 0.02-0.42) after one year than patients who did not have surgery. At two years, the differences in symptoms (OR: 0.25; 95%CI: 0.06-0.94) and signs (OR: 0.04; 95%CI: 0.002-0.33) persisted. CONCLUSIONS: Patients with UEDVT and TOS were younger and had less comorbidities than those without. Surgical resection of the first rib was associated with a lower proportion of patients developing PTS one and two years later.

Risk of recurrent venous thromboembolism in patients with autoimmune diseases: data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry.

Autoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03-1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks.

Venous thromboembolism in solid-organ transplant recipients: Findings from the RIETE registry.

BACKGROUND: Venous thromboembolism (VTE) represents a relevant cause of morbidity in patients with solid-organ transplant (SOT), but there are scarce data on the management and outcomes in these patients. METHODS: RIETE is a worldwide, ongoing observational registry of patients with objectively confirmed, acute VTE. We used the RIETE database to compare the clinical characteristics, treatment and outcomes in SOT recipients vs. non-recipients. RESULTS: From January 2001 to December 2019, 83,210 patients were enrolled in RIETE. Of these, 329 (0.4%) were SOT recipients: in the kidney 221, liver 41, lung 28 and heart 25. Median duration of anticoagulation was similar in SOT recipients and non-recipients (174 vs. 182 days). During anticoagulation, 1180 patients developed deep vein thrombosis (DVT) recurrences, 1028 pulmonary embolism (PE) recurrences, 2392 had major bleeding, 3119 non-major bleeding and 8157 died. SOT recipients had a higher rate of major bleeding (hazard ratio [HR]: 2.55; 95% CI: 1.62-3.84) and clinically relevant non-major bleeding (HR: 1.94; 95% CI: 1.23-2.93) than non-recipients, with no differences in the rates of DVT recurrences (HR: 0.96; 95% CI: 0.30-2.32), PE recurrences (HR: 1.11; 95% CI: 0.35-2.67) or death (HR: 0.98; 95% CI: 0.67-1.40). On multivariable analysis, only liver transplant recipients were at an increased risk for major bleeding compared to non-recipients (adjusted HR: 3.17; 95% CI: 1.02-9.87). CONCLUSIONS: Treatment of VTE in SOT recipients is associated with an increased risk of bleeding compared to non-recipients. This is mainly due to the influence of liver transplant recipients. In non-liver SOT recipients, the risk for bleeding was similar to that in non-recipients.

Comparative clinical prognosis of massive and non-massive pulmonary embolism: A registry-based cohort study.

AIMS: Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. METHODS AND RESULTS: We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time-to-event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio [sHR] 1.72, 95% confidence interval [CI] 1.28-2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75-1.74) than non-massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non-massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51-1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82-16.24). CONCLUSION: In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.

Outcomes after Vena Cava Filter Use in Patients with Cancer-Associated Venous Thromboembolism and Contraindications to Anticoagulation.

BACKGROUND: The association between the use of inferior vena cava filters (IVCFs) and outcomes among patients with cancer-associated thromboembolism (CT) and contraindications to anticoagulation remains unclear. METHODS: In this prospective cohort study of patients with CT from the Registro Informatizado de la Enfermedad TromboEmbólica Registry, we assessed the association between IVCF insertion due to contraindication to anticoagulation and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent thromboembolism, and major bleeding rates through 30 days after initiation of treatment. We used propensity score matching to adjust for the likelihood of receiving a filter. For outcomes assessment, we implemented generalized estimating equation methods to incorporate the matched-pairs design, and adjusted for covariates that remained unbalanced after matching. RESULTS: Of the 17,005 patients with CT, 270 underwent IVCF placement because of contraindication to anticoagulation. Of those, 247 were successfully matched with 247 patients treated without a filter. Propensity score-matched pairs showed a nonsignificantly lower risk of all-cause death (12.2% vs. 17.0%; p = 0.13), and a significantly lower risk of PE-related mortality (0.8% vs. 4.0%; p = 0.04) for patients receiving IVCFs compared with those who did not. While there was no significant difference in the rate of major bleeding (6.1% vs. 5.7%; p = 0.85), risk-adjusted recurrent rates were higher for patients who received IVCFs compared with those who did not (7.3% vs. 3.2%; p = 0.05). CONCLUSION: In patients with CT and a contraindication to anticoagulation, IVCF insertion was associated with a lower risk of PE-related death, and a higher risk of recurrences.

Inferior vena cava agenesis in patients with lower limb deep vein thrombosis in the RIETE registry. When and why to suspect.

BACKGROUND: Limited data exist about the clinical presentation and outcomes of patients with inferior vena cava agenesis (IVCA) who develop deep vein thrombosis (DVT). METHODS: We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to compare clinical characteristics and outcomes of patients with lower limb DVT, according to the presence or absence of IVCA. Major outcomes included recurrent DVT, major bleeding and post-thrombotic syndrome (PTS). RESULTS: Among 50,744 patients with lower-limb DVT recruited in October 2018, 31 (0.06%) had IVCA. On multivariable analysis, patients aged < 30 years (odds ratio [OR]: 17.9; 95%CI: 7.05-45.3), with unprovoked DVT (OR: 2.49; 95%CI: 1.17-5.29), proximal (OR: 2.81; 95%CI: 1.05-7.53) or bilateral DVT (OR: 11.5; 95%CI: 4.75-27.8) were at increased risk to have IVCA. Patients with DVT and IVCA had lower odds to present with coexisting PE (OR: 0.22; 95%CI: 0.07-0.73). During the first year of follow-up, the rates of DVT recurrences (hazard ratio [HR]: 1.30; 95%CI: 0.07-6.43), pulmonary embolism (HR: 2.30; 95%CI: 0.11-11.4) or major bleeding (HR: 1.32; 95%CI: 0.07-6.50) were not significantly different with those with versus those without IVCA. One year after the index DVT, IVCA patients had a higher rate of skin induration (OR: 3.70; 95%CI: 1.30-9.52), collateral vein circulation (OR: 3.57; 95%CI: 1.42-8.79) or venous ulcer (OR: 5.87; 95%CI: 1.36-1.87) in the lower limb than those without IVCA. CONCLUSIONS: Certain clinical features such as unprovoked and bilateral proximal DVT in young patients should raise the suspicion for IVCA. Patients with IVCA had higher odds for symptoms of post-thrombotic syndrome.

Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with Proximal Lower Extremity Deep Vein Thrombosis.

Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lower-extremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority of DVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for chi-squared test comparing all three groups). Comorbidities were relatively similar in those with left-sided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.00-1.18). This difference in mortality did not persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients with bilateral DVT had a greater burden of comorbidities such as heart failure, and recent surgery compared with those with unilateral DVT (p < 0.001), and higher relative frequency of PE (48%), and 1-year mortality (24.1%). Worse outcomes in patients with bilateral DVT were attenuated but persisted after multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI: 1.43-1.87). Patients with bilateral DVT had worse outcomes during and after discontinuation of anticoagulation. There is a left-sided preponderance for proximal lower-extremity DVT. Compared with those with left-sided DVT, patients with right-sided DVT have slightly higher rates of PE. Bilateral DVT is associated with markedly worse short-term and 1-year outcomes.

Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism.

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.

Outcomes beyond the Third Month of Anticoagulation in Patients Aged >75 Years with a First Episode of Unprovoked Venous Thromboembolism.

Background The ideal duration of anticoagulant therapy in elderly patients with unprovoked venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE ( R egistro I nformatizado E nfermedad T rombo E mbólica) registry to compare the rate and severity of pulmonary embolism (PE) recurrences versus major bleeding beyond the third month of anticoagulation in patients >75 years with a first episode of unprovoked VTE. Results As of September 2017, 7,830 patients were recruited: 5,058 (65%) presented with PE and 2,772 with proximal deep vein thrombosis (DVT). During anticoagulant therapy beyond the third month (median, 113 days), 44 patients developed PE recurrences, 36 developed DVT recurrences, 101 had major bleeding, and 241 died (3 died of recurrent PE and 19 of bleeding). The rate of major bleeding was twofold higher than the rate of PE recurrences (2.05 [95% confidence interval, CI: 1.68-2.48] vs. 0.90 [95% CI: 0.66-1.19] events per 100 patient-years) and the rate of fatal bleeding exceeded the rate of fatal PE events (0.38 [95% CI: 0.24-0.58] vs. 0.06 [95% CI: 0.02-0.16] deaths per 100 patient-years). On multivariable analysis, patients who had bled during the first 3 months (hazard ratio [HR]: 4.32; 95% CI: 1.58-11.8) or with anemia at baseline (HR: 1.87; 95% CI: 1.24-2.81) were at increased risk for bleeding beyond the third month. Patients initially presenting with PE were at increased risk for PE recurrences (HR: 3.60; 95% CI: 1.28-10.1). Conclusion Prolonging anticoagulation beyond the third month was associated with more bleeds than PE recurrences. Prior bleeding, anemia, and initial VTE presentation may help decide when to stop therapy.

Gender-related differences in the outcome of patients with venous thromboembolism and thrombophilia.

BACKGROUND: In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. RESULTS: From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). CONCLUSIONS: During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.

Right heart thrombi in pulmonary embolism.

There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism.In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment.Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62-3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45-7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT.In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT.

Venous thromboembolism in centenarians: Findings from the RIETE registry.

BACKGROUND: The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. METHODS: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. RESULTS: Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. CONCLUSIONS: Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26-3.23), age >70 years (OR 1.15, 95% CI 1.06-1.24), immobility (OR 2.06, 95% CI 1.93-2.19), renal insufficiency (OR 2.42, 95% CI 2.15-2.71) and anemia (OR 1.75, 95% CI 1.65-1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64-2.06), immobility (OR 1.51, 95% CI 1.30-1.76) and metastases (OR 3.22, 95% CI 2.87-3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision.

Fondaparinux in the initial and long-term treatment of venous thromboembolism.

BACKGROUND: Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. METHODS: We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. RESULTS: Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). CONCLUSIONS: An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients.