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

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 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

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

Fatal events in cancer patients receiving anticoagulant therapy for venous thromboembolism

none144siIn cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911(18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ±210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy.openFarge D.; Trujillo-Santos J.; Debourdeau P.; Bura-Riviere A.; Rodriguez-Beltran E.M.; Nieto J.A.; Peris M.L.; Zeltser D.; Mazzolai L.; Hij A.; Monreal M.; Durante A.; Alcalde M.; Arcelus J.I.; Ballaz A.; Barba R.; Barron M.; Barron-Andres B.; Bascunana J.; Bedate P.; Blanco-Molina A.; Bueso T.; Casado I.; Conget F.; Del Molino F.; Del Toro J.; Falga C.; Fernandez-Capitan C.; Fuentes M.I.; Gallego P.; Garcia J.; Garcia-Bragado F.; Gavin O.; Gomez V.; Gonzalez J.; Gonzalez-Bachs E.; Grau E.; Guil M.; Guijarro R.; Gutierrez J.; Hernandez L.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Jimenez S.; Lobo J.L.; Lopez-Jimenez L.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Luque J.M.; Madridano O.; Macia M.; Maestre A.; Marchena P.J.; Martin M.; Monreal M.; Mora J.M.; Munoz F.J.; Nauffal M.D.; Nieto J.A.; Nunez M.J.; Ogea J.L.; Otero R.; Pedrajas J.M.; Peris M.L.; Riera-Mestre A.; Rivas A.; Rodriguez-Davila M.A.; Roman P.; Rosa V.; Ruiz J.; Ruiz-Ribo M.D.; Ruiz-Gamietea A.; Ruiz-Gimenez N.; Sahuquillo J.C.; Samperiz A.; Sanchez Munoz-Torrero J.F.; Soler S.; Tiberio G.; Tilvan R.M.; Tolosa C.; Trujillo J.; Uresandi F.; Valdes M.; Valero B.; Valle R.; Vela J.; Vidal G.; Villalobos A.; Villalta J.; Gadelha T.; Maly R.; Hirmerova J.; Tomko T.; Bertoletti L.; Bura-Riviere A.; Farge-Bancel D.; Grange C.; Hij A.; Mahe I.; Merah A.; Quere I.; Schellong S.; Babalis D.; Papadakis M.; Tzinieris I.; Faul J.; Braester A.; Brenner B.; Tzoran I.; Zeltser D.; Barillari G.; Ciammaichella M.; Dalla Valle F.; Di Micco P.; Duce R.; Maida R.; Pasca S.; Piovella C.; Poggio R.; Prandoni P.; Quintavalla R.; Rocci A.; Rota L.; Schenone A.; Tiraferri E.; Tonello D.; Tufano A.; Visona A.; Zalunardo B.; Brinquinho M.; Gomes D.; Goncalves F.; Santos M.; Saraiva M.; Bosevski M.; Kovacevic D.; Alatri A.; Aujeski D.; Bounameaux H.; Calanca L.; Mazzolai L.; Caprini J.Farge, D.; Trujillo-Santos, J.; Debourdeau, P.; Bura-Riviere, A.; Rodriguez-Beltran, E. M.; Nieto, J. A.; Peris, M. L.; Zeltser, D.; Mazzolai, L.; Hij, A.; Monreal, M.; Durante, A.; Alcalde, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barron, M.; Barron-Andres, B.; Bascunana, J.; Bedate, P.; Blanco-Molina, A.; Bueso, T.; Casado, I.; Conget, F.; Del Molino, F.; Del Toro, J.; Falga, C.; Fernandez-Capitan, C.; Fuentes, M. I.; Gallego, P.; Garcia, J.; Garcia-Bragado, F.; Gavin, O.; Gomez, V.; Gonzalez, J.; Gonzalez-Bachs, E.; Grau, E.; Guil, M.; Guijarro, R.; Gutierrez, J.; Hernandez, L.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Jimenez, S.; Lobo, J. L.; Lopez-Jimenez, L.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Luque, J. M.; Madridano, O.; Macia, M.; Maestre, A.; Marchena, P. J.; Martin, M.; Monreal, M.; Mora, J. M.; Munoz, F. J.; Nauffal, M. D.; Nieto, J. A.; Nunez, M. J.; Ogea, J. L.; Otero, R.; Pedrajas, J. M.; Peris, M. L.; Riera-Mestre, A.; Rivas, A.; Rodriguez-Davila, M. A.; Roman, P.; Rosa, V.; Ruiz, J.; Ruiz-Ribo, M. D.; Ruiz-Gamietea, A.; Ruiz-Gimenez, N.; Sahuquillo, J. C.; Samperiz, A.; Sanchez Munoz-Torrero, J. F.; Soler, S.; Tiberio, G.; Tilvan, R. M.; Tolosa, C.; Trujillo, J.; Uresandi, F.; Valdes, M.; Valero, B.; Valle, R.; Vela, J.; Vidal, G.; Villalobos, A.; Villalta, J.; Gadelha, T.; Maly, R.; Hirmerova, J.; Tomko, T.; Bertoletti, L.; Bura-Riviere, A.; Farge-Bancel, D.; Grange, C.; Hij, A.; Mahe, I.; Merah, A.; Quere, I.; Schellong, S.; Babalis, D.; Papadakis, M.; Tzinieris, I.; Faul, J.; Braester, A.; Brenner, B.; Tzoran, I.; Zeltser, D.; Barillari, G.; Ciammaichella, M.; Dalla Valle, F.; Di Micco, P.; Duce, R.; Maida, R.; Pasca, S.; Piovella, C.; Poggio, R.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Rota, L.; Schenone, A.; Tiraferri, E.; Tonello, D.; Tufano, A.; Visona, A.; Zalunardo, B.; Brinquinho, M.; Gomes, D.; Goncalves, F.; Santos, M.; Saraiva, M.; Bosevski, M.; Kovacevic, D.; Alatri, A.; Aujeski, D.; Bounameaux, H.; Calanca, L.; Mazzolai, L.; Caprini, J

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism

International audienceOBJECTIVES: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes.METHODS:Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery.RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058).CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation