Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

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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 longterm fondaparinux. Our small sample does not allowto derive relevant conclusions on the use of fondaparinux in cancer patients

Treatment of Right Heart Thrombi Associated with Acute Pulmonary Embolism

Background Evidence-based recommendations do not adequately address the treatment of right heart thrombi in patients who present with acute symptomatic pulmonary embolism. Methods This study included patients who had acute pulmonary embolism associated with right heart thrombi and participated in the Registro Informatizado de la Enfermedad TromboEmb\uf3lica registry. We assessed the effectiveness of anticoagulation versus reperfusion treatment for the outcomes of all-cause mortality, pulmonary embolism\u2013related mortality, recurrent venous thromboembolism, and major bleeding rates through 30 days after initiation of pulmonary embolism treatment. We used propensity score matching to adjust for the likelihood of receiving reperfusion treatment. Results Of 325 patients with pulmonary embolism and right heart thrombi, 255 (78%; 95% confidence interval, 74-83) received anticoagulation and 70 (22%; 95% confidence interval, 17-26) also received reperfusion treatment. Propensity score\u2013matched pairs analyses did not detect a statistically lower risk of all-cause death (6.2% vs 14%, P&nbsp;= .15) or pulmonary embolism\u2013related mortality (4.7% vs 7.8%; P&nbsp;= .47) for reperfusion compared with anticoagulation. Of the patients who received reperfusion treatment, 6.2% had a recurrence during the study follow-up period, compared with 0% of those who received anticoagulation (P&nbsp;= .049). The incidence of major bleeding events was not statistically different between the 2 treatment groups (3.1% vs 3.1%; P&nbsp;= 1.00). Conclusions In patients with pulmonary embolism and right heart thrombi, no significant difference was found between reperfusion therapy and anticoagulant therapy for mortality and bleeding. The risk of recurrences was significantly higher for reperfusion therapy compared with anticoagulation. Right heart thrombi may not warrant riskier interventions than standard anticoagulation

Predictors of active cancer thromboembolic outcomes: RIETE experience of the Khorana score in cancer-associated thrombosis

158sinoneEven though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1-2 points and 1145 (14 %) scored ≥points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99-7.63), 11.2 (95 %CI: 9.91-12.7) and 19.4 (95 %CI: 15.4-24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13-6.56), 10.3 (95 %CI: 9.02-11.7) and 19.4 (95 %CI: 15.4-24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8-28.0), 58.5 (95 %CI: 55.5-61.7) and 120 (95 %CI: 110-131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50-0.56) for recurrent VTE, 0.56 (95 %CI: 0.54-0.59) for major bleeding and 0.54 (95 %CI: 0.52-0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.noneTafur A.J.; Caprini J.A.; Cote L.; Trujillo-Santos J.; del Toro J.; Garcia-Bragado F.; Tolosa C.; Barillari G.; Visona A.; Monreal M.; Adarraga M.D.; Aibar M.A.; Alfonso M.; Arcelus J.I.; Ballaz A.; Barba R.; Barron M.; Barrn-Andres B.; Bascunana J.; Blanco-Molina A.; Canas I.; Chic N.; del Pozo R.; Diaz-Pedroche M.C.; Diaz-Peromingo J.A.; Falga C.; Fernandez-Aracil C.; Fernandez-Capitan C.; Fidalgo M.A.; Font C.; Font L.; Gallego P.; Garcia I.; Garcia M.A.; Garcia-Rodenas M.; Gavin O.; Gomez C.; Gomez V.; Gonzalez J.; Grau E.; Grimon A.; Guijarro R.; Guirado L.; Gutierrez J.; Hernandez-Comes G.; Hernandez-Blasco L.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Jimenez J.; Joya M.D.; Llamas P.; Lobo J.L.; Lopez P.; Lopez-Jimenez L.; Lopez-Reyes R.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Lumbierres M.; Marchena P.J.; Martin-Martos F.; Mellado M.; Nieto J.A.; Nieto S.; Nunez A.; Nunez M.J.; Otalora S.; Otero R.; Ovejero A.; Pedrajas J.M.; Perez G.; Perez-Ductor C.; Peris M.L.; Pons I.; Porras J.A.; Reig O.; Riera-Mestre A.; Riesco D.; Rivas A.; Rodriguez M.; Rodriguez-Davila M.A.; Rosa V.; Ruiz-Artacho P.; Ruiz-Gimenez N.; Sahuquillo J.C.; Sala-Sainz M.C.; Samperiz A.; Sanchez-Martinez R.; Sanz O.; Soler S.; Sopena B.; Surinach J.M.; Torres M.I.; Uresandi F.; Usandizaga E.; Valero B.; Valle R.; Vela J.; Velez-Mendizabal E.; Vidal G.; Vila M.; Villalobos A.; Xifre B.; Vanassche T.; Verhamme P.; Yoo H.H.B.; Wells P.; Hirmerova J.; Maly R.; Salgado E.; Bertoletti L.; Bura-Riviere A.; Falvo N.; Farge-Bancel D.; Hij A.; Mahe I.; Moustafa F.; Braester A.; Brenner B.; Tzoran I.; Antonucci G.; Bilora F.; Bortoluzzi C.; Brandolin B.; Bucherini E.; Candeloro G.; Cattabiani C.; Ciammaichella M.; Dentali F.; Di Micco P.; Duce R.; Giorgi-Pierfranceschi M.; Grandone E.; Imbalzano E.; Lessiani G.; Maida R.; Mastroiacovo D.; Pace F.; Parisi R.; Pellegrinet M.; Pesavento R.; Pinelli M.; Poggio R.; Prandoni P.; Quintavalla R.; Rocci A.; Tiraferri E.; Tonello D.; Tufano A.; Visona A.; Gibietis V.; Skride A.; Vitola B.; Bosevski M.; Zdraveska M.; Bounameaux H.; Mazzolai L.Tafur, A. J.; Caprini, J. A.; Cote, L.; Trujillo-Santos, J.; del Toro, J.; Garcia-Bragado, F.; Tolosa, C.; Barillari, G.; Visona, A.; Monreal, M.; Adarraga, M. D.; Aibar, M. A.; Alfonso, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barron, M.; Barrn-Andres, B.; Bascunana, J.; Blanco-Molina, A.; Canas, I.; Chic, N.; del Pozo, R.; Diaz-Pedroche, M. C.; Diaz-Peromingo, J. A.; Falga, C.; Fernandez-Aracil, C.; Fernandez-Capitan, C.; Fidalgo, M. A.; Font, C.; Font, L.; Gallego, P.; Garcia, I.; Garcia, M. A.; Garcia-Rodenas, M.; Gavin, O.; Gomez, C.; Gomez, V.; Gonzalez, J.; Grau, E.; Grimon, A.; Guijarro, R.; Guirado, L.; Gutierrez, J.; Hernandez-Comes, G.; Hernandez-Blasco, L.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Jimenez, J.; Joya, M. D.; Llamas, P.; Lobo, J. L.; Lopez, P.; Lopez-Jimenez, L.; Lopez-Reyes, R.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Lumbierres, M.; Marchena, P. J.; Martin-Martos, F.; Mellado, M.; Nieto, J. A.; Nieto, S.; Nunez, A.; Nunez, M. J.; Otalora, S.; Otero, R.; Ovejero, A.; Pedrajas, J. M.; Perez, G.; Perez-Ductor, C.; Peris, M. L.; Pons, I.; Porras, J. A.; Reig, O.; Riera-Mestre, A.; Riesco, D.; Rivas, A.; Rodriguez, M.; Rodriguez-Davila, M. A.; Rosa, V.; Ruiz-Artacho, P.; Ruiz-Gimenez, N.; Sahuquillo, J. C.; Sala-Sainz, M. C.; Samperiz, A.; Sanchez-Martinez, R.; Sanz, O.; Soler, S.; Sopena, B.; Surinach, J. M.; Torres, M. I.; Uresandi, F.; Usandizaga, E.; Valero, B.; Valle, R.; Vela, J.; Velez-Mendizabal, E.; Vidal, G.; Vila, M.; Villalobos, A.; Xifre, B.; Vanassche, T.; Verhamme, P.; Yoo, H. H. B.; Wells, P.; Hirmerova, J.; Maly, R.; Salgado, E.; Bertoletti, L.; Bura-Riviere, A.; Falvo, N.; Farge-Bancel, D.; Hij, A.; Mahe, I.; Moustafa, F.; Braester, A.; Brenner, B.; Tzoran, I.; Antonucci, G.; Bilora, F.; Bortoluzzi, C.; Brandolin, B.; Bucherini, E.; Candeloro, G.; Cattabiani, C.; Ciammaichella, M.; Dentali, F.; Di Micco, P.; Duce, R.; Giorgi-Pierfranceschi, M.; Grandone, E.; Imbalzano, E.; Lessiani, G.; Maida, R.; Mastroiacovo, D.; Pace, F.; Parisi, R.; Pellegrinet, M.; Pesavento, R.; Pinelli, M.; Poggio, R.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Tiraferri, E.; Tonello, D.; Tufano, A.; Visona, A.; Gibietis, V.; Skride, A.; Vitola, B.; Bosevski, M.; Zdraveska, M.; Bounameaux, H.; Mazzolai, L

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

Introduction: Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugsmay increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis. Methods: Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course. Results: 1178 patientswho received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p < 0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p < 0.05) or death (23.6 vs. 13.9 deaths per 100 patientsyears; p < 0.01). No differences in the rate of major bleeding or recurrent VTEwere revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate. Conclusion: Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations

Characteristics, treatment patterns and outcomes of patients presenting with venous thromboembolic events after knee arthroscopy in the RIETE Registry

Knee arthroscopy is the most common orthopedic procedure worldwide. While incidence of post-arthroscopy venous thromboembolic events (VTE) is low, treatment patterns and patient outcomes have not been described. Patients from the "Registro Informatizado Enfermedad TromboEmbolica" who had confirmed post-arthroscopy VTE were compared to patients with provoked, post bone-fracture, and to patients with unprovoked VTE. Baseline characteristics, presenting signs and symptoms, treatment and outcomes including recurrent VTE, bleeds or death were compared. A total of 101 patients with post-arthroscopy VTE and 19,218 patients with unprovoked VTE were identified. Post-arthroscopy patients were younger (49.5 vs. 66 years, P\u2009&lt;\u20090.0001) and had less history of VTE [5.9% vs. 20%, OR 0.26 (0.11-0.59)]. Among patients with isolated DVT, there were fewer proximal DVT in the post-arthroscopy group [40% vs. 86%, OR 0.11 (0.06-0.19)]. Treatment duration was shorter in the post-arthroscopy group (174\u2009\ub1\u2009140 vs. 311\u2009\ub1\u2009340&nbsp;days, P\u2009&lt;\u20090.0001) and more often with DOAC [OR 3.67 (1.95-6.89)]. Recurrent VTE occurred in 6.18 (1.96-14.9) and 11.9 (11.0-12.8) per 100 patient years [HR 0.52 (0.16-1.26)] after treatment in the post-arthroscopy and unprovoked groups, respectively. Recurrent VTE occurred in 5.17 (1.31-14.1) per 100 patient years in a separate post bone-fracture group (n\u2009=\u2009147), also not statistically different than the post-arthroscopy recurrence rate. After anticoagulation cessation, some patients post-knee arthroscopy develop VTE. While our small sample size precludes drawing firm conclusions, this signal should warrant further research into the optimal treatment duration for these patients, as some patients may be at increased risk for long-term recurrence

A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the lower limbs

BACKGROUND: No prior studies have identified which patients with deep vein thrombosis in the lower limbs are at a low risk for adverse events within the first week of therapy. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmb\uf3lica (RIETE) to identify patients at low risk for the composite outcome of pulmonary embolism, major bleeding, or death within the first week. We built a prognostic score and compared it with the decision to treat patients at home. RESULTS: As of December 2013, 15,280 outpatients with deep vein thrombosis had been enrolled. Overall, 5164 patients (34%) were treated at home. Of these, 12 (0.23%) had pulmonary embolism, 8 (0.15%) bled, and 4 (0.08%) died. On multivariable analysis, chronic heart failure, recent immobility, recent bleeding, cancer, renal insufficiency, and abnormal platelet count independently predicted the risk for the composite outcome. Among 11,430 patients (75%) considered to be at low risk, 15 (0.13%) suffered pulmonary embolism, 22 (0.19%) bled, and 8 (0.07%) died. The C-statistic was 0.61 (95% confidence interval [CI], 0.57-0.65) for the decision to treat patients at home and 0.76 (95% CI, 0.72-0.79) for the score (P = .003). Net reclassification improvement was 41% (P < .001). Integrated discrimination improvement was 0.034 for the score and 0.015 for the clinical decision (P < .001). CONCLUSIONS: Using 6 easily available variables, we identified outpatients with deep vein thrombosis at low risk for adverse events within the first week. These data may help to safely treat more patients at home. This score, however, should be validated

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs. The frequency, clinical characteristics and outcome of these patients have not been reported in real life. Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non-fragile. 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

Analysis of noncatheter-associated upper extremity deep venous thrombosis from the RIETE registry

Objective We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients. Methods The RIETE registry (Registro Informatizado de Enfermedad TromboEmb\uf3lica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hemorrhage. Multivariate analysis was performed using stepwise logistic regression. Results Of the 1100 patients who met the study criteria, 580 (53%) were male. The mean age of the patients was 50&nbsp;\ub1 20 years, and overall patient survival at 1 year was 85%. Recurrent VTE occurred in 59 patients (5.4%). Of these, 46 patients (4%) had recurrent DVT, 10 (0.9%) had a PE following UEDVT diagnosis, and 3 (0.3%) had both. PE was fatal in three patients (0.3%). Bleeding occurred in 50 patients (4.5%), major bleeding in 19 patients (1.7%), and fatal bleeding in 6 patients (0.5%). On multivariate analysis, malignant disease was associated with VTE recurrence (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.04-3.45; P&nbsp;&lt;.04), whereas hemorrhage was associated with age (OR, 1.03; 95% CI, 1.01-1.05; P&nbsp;=.002) and malignant disease (OR, 2.53; 95% CI, 1.34-4.76; P&nbsp;&lt;.005). Hemorrhage and recurrent VTE were also significantly associated (OR, 2.79; 95% CI, 1.16-6.76; P&nbsp;&lt;.03). Conclusions PE following non-CA-UEDVT is rare. Malignant disease was associated with VTE recurrence. Age and malignant disease were associated with hemorrhage, and VTE recurrence was associated with hemorrhage. Further prospective studies should be undertaken to best determine length of anticoagulation treatment for the varied populations of patients with UEDVT