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.

Predictors of use of direct oral anticoagulants in patients with venous thromboembolism: Findings from the Registro Informatizado Enfermedad Tromboembólica registry.

Background: Current guidelines recommend the use of direct oral anticoagulants (DOACs) for patients with venous thromboembolism (VTE). However little is known about the use of DOACs in daily practice. Methods: We used the RIETE registry to identify predictors of use of DOACs for initial and/or long-term therapy of VTE based on patient-related factors, institution-related factors or over time. Results: Among 41,678 patients from March 2013 to September 2021, 12,286 (29%) used DOACs: for initial therapy 6,456; for long-term therapy 12,046. On multivariable analysis, independent predictors were: age < 65 years (odds ratio [OR]: 1.30; 95% CI: 1.23-1.38), body weight <50 kg (OR: 0.54; 95% CI: 0.45-0.65) or >120 kg (OR: 0.64; 95% CI: 0.53-0.77), initial VTE presentation as pulmonary embolism (OR: 1.18; 95% CI: 1.13-1.25), recent bleeding (OR: 0.53; 95% CI: 0.45-0.63), renal insufficiency (OR: 0.44; 95% CI: 0.38-0.51), liver cirrhosis (OR: 0.32; 95% CI: 0.20-0.52), thrombocytopenia (OR: 0.40; 95% CI: 0.34-0.49), atrial fibrillation (OR: 1.58; 95% CI: 1.42-1.75) and prior VTE (OR: 1.14; 95% CI: 1.06-1.22). The DOACs were more likely used in other European countries (OR: 8.97; 95% CI: 8.49-9.49), America (OR: 6.35; 95% CI: 5.67-7.11) or in other countries of the world (OR: 2.99; 95% CI: 2.70-3.31) than in Spain, and progressively increased from 2013-2015 to 2016-2018 (OR: 2.78; 95% CI: 2.62-2.95) and 2019-2021 (OR: 6.36; 95% CI: 5.95-6.80). Conclusion: In this large multinational VTE registry, variations were observed in the use of DOACs according to patient or country factors, and over time. The safety, costs, and influence of the DOACs on VTE-related outcomes in daily practice warrant further investigation.

Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

Clinical characteristics, time course, and outcomes of major bleeding according to bleeding site in patients with venous thromboembolism.

BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

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.

Clinical characteristics and 3-month outcomes in cancer patients with incidental versus clinically suspected and confirmed pulmonary embolism.

BACKGROUND: Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared. METHODS: We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PE versus those with clinically suspected and confirmed PE. The primary outcome was 90-day all-cause mortality. Secondary outcomes were PE-related mortality, symptomatic PE recurrences and major bleeding. RESULTS: From July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95% versus 90%) received low-molecular-weight heparin therapy. During the first 90 days, 598 patients died, including 42 from PE. Patients with incidental PE had a lower all-cause mortality rate than those with suspected and confirmed PE (11% versus 22%; OR 0.43, 95% CI 0.34-0.54). Results were consistent for PE-related mortality (0.3% versus 1.7%; OR 0.18, 95% CI 0.06-0.59). Multivariable analysis confirmed that patients with incidental PE were at lower risk of death (adjusted OR 0.43, 95% CI 0.34-0.56). Overall, 29 (0.9%) patients developed symptomatic PE recurrences, and 122 (3.8%) had major bleeding. There were no significant differences in PE recurrences (OR 0.62, 95% CI 0.25-1.54) or major bleeding (OR 0.78, 95% CI 0.51-1.18). CONCLUSIONS: Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.

Obstructive sleep apnea is associated with worse clinical-radiological risk scores of pulmonary embolism.

Obstructive sleep apnea is a risk factor for pulmonary embolism, although its association with pulmonary embolism severity is unknown. Our objective was to study if obstructive sleep apnea is associated with worse pulmonary embolism severity scores and greater extent of arterial obstruction. In consecutive pulmonary embolism patients, we performed respiratory polygraphy and recorded sleep characteristics, classical risk factors for pulmonary embolism and physical activity 6-12 months after the pulmonary embolism episode. Simplified Geneva Prognostic Score and Pulmonary Embolism Severity Index were calculated at the time of the pulmonary embolism diagnosis. The Pulmonary Artery Obstruction Index and the right ventricle to left ventricle diameter ratio were measured by computed tomography pulmonary angiography. We included 120 patients, of whom 45.8% had moderate-severe obstructive sleep apnea (apnea-hypopnea index > 15 hr-1 ). There was a larger proportion of moderate-severe obstructive sleep apnea patients in the third and fourth Pulmonary Artery Obstruction Index quartiles and in the III-V Pulmonary Embolism Severity Index levels compared with apnea-hypopnea index < 15 hr-1 group. However, no differences were found between the proportion of patients with or without moderate-severe obstructive sleep apnea in their stratification by simplified Geneva Prognostic Score. The mean adjusted values of the simplified Geneva Prognostic Score, Pulmonary Embolism Severity Index and Pulmonary Artery Obstruction Index scores were higher in the apnea-hypopnea index > 15 hr-1 group (p < .05). Multiple linear regression analysis identified apnea-hypopnea index as the only independent factor related to Pulmonary Artery Obstruction Index and Pulmonary Embolism Severity Index, whereas desaturation index was associated with simplified Geneva Prognostic Score. Patients with pulmonary embolism and moderate-severe obstructive sleep apnea had greater pulmonary artery obstruction as well as more pulmonary embolism severity, assessed by both the simplified Geneva Prognostic Score and the Pulmonary Embolism Severity Index, compared with patients with apnea-hypopnea index ≤ 15 hr-1 . Moreover, these prognostic indices were independently related to sleep parameters.

Venous thromboembolism in young adults: Findings from the RIETE registry.

BACKGROUND: Little is known on the clinical characteristics, risk factors and outcomes during anticoagulation in young patients with acute venous thromboembolism (VTE). METHODS: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to assess the clinical characteristics, risk factors and outcomes during anticoagulation in VTE patients aged 10-24 years. Data were separately analyzed according to initial presentation and gender. RESULTS: Of 76,719 patients with VTE, 1571 (2.0%) were aged 10-24 years. Of these, 989 (63%) were women and 669 (43%) presented with pulmonary embolism (PE). Most women were using estrogens (680, 69%) or were pregnant (101, 10%), while 59% of men had unprovoked VTE. Women were more likely to present with PE (48% vs. 34%). The majority (87%) of PE patients had Sat O2 levels ≥90% at baseline. The vast majority (97%) of PE patients were at low risk according to the PESI score, many (90%) at very low risk. During the course of anticoagulation (median, 192 days), 40 patients had VTE recurrences, 17 had major bleeding and 10 died (3 died of PE). Women had as many VTE recurrences as major bleeds (15 vs. 14 events), while men had many more VTE recurrences than major bleeding (25 vs. 3 events). CONCLUSIONS: VTE is associated with low risk of short-term mortality in young adults. Noticeable gender differences exist in the risk factor profile and the risk of VTE recurrences and major bleeding in the course of anticoagulation.

Mortality after pulmonary embolism in patients with diabetes. Findings from the RIETE registry.

BACKGROUND: Among patients presenting with pulmonary embolism (PE), those with diabetes are at increased risk to die than those without diabetes. The reasons have not been identified. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to compare the mortality rate and the causes of death during anticoagulation in patients with PE according to the presence or absence of diabetes. METHODS: A matched retrospective cohort study from consecutively enrolled patients in RIETE, from 179 hospitals in 24 countries. For each patient with diabetes we selected two patients with no diabetes matched by age, sex and year of diagnosis of the PE. RESULTS: As of September 2017, there were 2010 PE patients with diabetes and two age-and-gender matched controls. Mean age was 74 ±â€¯11 years, 46% were men. Patients with diabetes were more likely to have co-morbidities, to be using antiplatelets and to have more severe PE. During anticoagulation (median, 219 days), patients with diabetes had a higher mortality (hazard ratio [HR]: 1.45; 95% confidence intervals [CI]: 1.25-1.67) and a higher rate of arterial ischemic events (HR: 2.89; 95%CI: 1.71-4.94) than those without diabetes. On multivariable analysis, diabetes was not associated with an increased risk for death (HR: 1.26; 95%CI: 0.97-1.63). We also failed to find differences according to the use of antiplatelet drugs concomitantly. CONCLUSIONS: In our cohort of patients with PE, diabetes was not an independent predictor for death. The influence of arterial events or antiplatelet drugs (if any) was low.

Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

In patients receiving anticoagulant therapy for venous thromboembolism (VTE), the important issue of anemia influence on the risk of bleeding has not been consistently studied. We used the large registry data RIETE (Registro Informatizado Enfermedad Tromboembólica) to compare the rate of major bleeding in patients receiving anticoagulant therapy for VTE according to the presence or absence of anemia at baseline. Patients with or without cancer were separately studied. Until August 2016, 63492 patients had been enrolled. Of these, 21652 (34%) had anemia and 14312 (23%) had cancer. Anemia was found in 57% of the patients with cancer and in 28% without (odds ratio 3.46; 95% CI 3.33-3.60). During the course of anticoagulant therapy, 680 patients with cancer had a major bleeding event (gastrointestinal tract 43%, intracranial 14%, hematoma 12%). Cancer patients with anemia had a higher rate of major bleeding (rate ratio [RR]: 2.52; 95% CI 2.14-2.97) and fatal bleeding (RR 2.73; 95% CI 1.95-3.86) than those without anemia. During the course of anticoagulation, 1133 patients without cancer had major bleeding (gastrointestinal tract 32%, hematoma 24%, intracranial 21%). Patients with anemia had a higher rate of major bleeding (RR 2.84; 95% CI 2.52-2.39) and fatal bleeding (RR 2.76; 95% CI 2.07-3.67) than those without. On a multivariable analysis, anemia independently predicted the risk for major bleeding in patients with and without cancer (hazard ratios: 1.66; 95% CI 1.40-1.96 and 1.95; 95% CI 1.72-2.20, respectively). During anticoagulation for VTE, both cancer- and non-cancer anemic patients had a higher risk for major bleeding than those without anemia. In anemic patients (with or without cancer), the rate of major bleeding during the course of anticoagulant therapy exceeded the rate of VTE recurrences. In patients without anemia the rate of major bleeding was lower than the rate of VTE recurrences.

Predictors of Post-Thrombotic Ulcer after Acute DVT: The RIETE Registry.

In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilitating and end-stage clinical expression of the post-thrombotic syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have not been identified.We used the international observational RIETE registry to assess the evolution of PTS signs and symptoms during a 3-year follow-up period and to identify independent predictors of PTS ulcer at 1 year in patients with acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2 and 3 years were 2.7% (n = 50), 4.3% (n = 54) and 7.1% (n = 60), respectively. The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable (≈40%), while the proportion of patients with PTS signs increased slightly over time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio [OR] = 5.5 [2.8-10.9]), diabetes (OR = 2.3 [1.1-4.7]), pre-existing leg varicosities (OR = 3.2 [1.7-6.1]) and male sex (OR = 2.5 [1.3-5.1]) independently increased the risk of PTS ulcer at 1 year. Obesity also increased the risk but failed to reach statistical significance (OR = 1.8 [0.9-3.3]). DVT treatment characteristics (duration or drug) did not influence the risk.Our results evidence that after acute DVT, pre-existing leg varicosities, prior venous thromboembolism, diabetes and male gender independently increased the risk for PTS ulcer. This suggests that clinicians should consider strategies aimed to prevent ulcers in high-risk DVT patients, such as preventing VTE recurrence, use of stockings in those with pre-existing venous insufficiency, careful monitoring of diabetic patients and encouraging weight loss in obese patients.

Gender differences in patients with venous thromboembolism and five common sites of cancer.

BACKGROUND: The outcome of cancer patients with venous thromboembolism (VTE) may differ according to gender. METHODS: We used the RIETE database to compare the rate of VTE recurrences, major bleeding and mortality in patients with lung, colorectal, pancreatic, hematologic or gastric cancer during the course of anticoagulation, according to gender. RESULTS: As of January 2016, 11,055 patients with active cancer were enrolled: 1,727 had lung cancer, 1,592 colorectal, 840 hematologic, 517 pancreatic and 459 had gastric cancer. Compared with men (N = 3,130), women (N = 2,005) were more likely to have colorectal, pancreatic or hematologic cancer, and less likely to have lung cancer. Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH), but women received higher daily doses per body weight. Then, 66% kept receiving LMWH for long-term therapy. During the course of anticoagulation, 302 patients developed recurrent VTE, 220 bled and 1,749 died. Compared with men, women had a similar rate of VTE recurrences or major bleeding, and a lower mortality (risk ratio [RR]: 0.90; 95% CI: 0.82-0.99). When separately comparing outcomes according to cancer site, women with lung cancer had a lower mortality (RR: 0.79; 95% CI: 0.70-0.92), those with colorectal cancer had a higher mortality (RR: 1.25; 95% CI: 1.02-1.54) and those with gastric cancer had a higher rate of VTE recurrences than men (RR: 2.47; 95% CI: 1.04-5.89). CONCLUSIONS: VTE women with lung, colorectal, pancreatic, haematological or gastric cancer experienced a similar outcome during the course of anticoagulant therapy than men with similar cancers.

Analysis of clinical factors affecting the rates of fatal pulmonary embolism and bleeding in cancer patients with venous thromboembolism.

BACKGROUND: In cancer patients with symptomatic venous thromboembolism (VTE) (deep-vein thrombosis (DVT) and/or pulmonary embolism (PE)), clinical factors that influence the benefit-risk balance of anticoagulation need to be identified so treatment intensity and duration can be optimally adjusted for the individual patient. METHODS: Using clinical data for cancer patients with VTE obtained from the RIETE registry, we compared how rates of fatal PE and fatal bleeding during and after anticoagulation vary depending on patients' clinical characteristics. RESULTS: Data were analysed from the 10,962 cancer patients with VTE (5,740 with PE with or without DVT; 5,222 with DVT alone) in RIETE registry as of March 2016. Fatal PE occurred in 2.18% of patients, while fatal bleedings occurred in 1.55%. During the 12 months from initial VTE, fatal PE was the most common cause of death, after disseminating cancer, and bleeding the fourth most common. In patients initially presenting with PE, fatal PE during anticoagulation was 4-fold more frequent than fatal bleeding (204 vs 51 deaths) and occurred mostly during the first month of treatment (196/223, 88%). In patients initially presenting with DVT, fatal PE was 3-fold lower than fatal bleeding during (25 vs 85 deaths) and after anticoagulation treatment (8 vs 37 deaths). During the 12-month follow-up, other characteristics of cancer patients with VTE were identified as more common in fatal cases of PE and/or bleeding than in surviving cases. INTERPRETATION: Baseline clinical characteristics may determine anticoagulation outcomes in cancer patients with VTE and should be further investigated as possible factors for guiding changes in current practices of anticoagulation, such as adjusting anticoagulation intensity and duration in selected patients.

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism.

BACKGROUND: Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. OBJECTIVES: To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non-fragile patients with VTE. METHODS: Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. RESULTS: From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37-0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10-1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16-2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05-12.4), all-cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75-2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10-2.85) than the non-fragile. CONCLUSIONS: In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non-fragile.