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Herve Decousus - One of the best experts on this subject based on the ideXlab platform.
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spontaneous acute Superficial Vein Thrombosis of the legs do we really need to treat
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Laurent Bertoletti, Herve Decousus, Paul FrappéAbstract:Summary. Spontaneous acute Superficial Vein Thrombosis (SVT) of the leg is now generally recognized as an integral component of venous thromboembolic disease with potentially severe consequences. However, the relatively low grades of some current international recommendations and uncertainty regarding the cost-effectiveness of available therapies may prompt questioning of the real need to treat patients with SVT and explain the persisting heterogeneity of their management in practise. Yet several studies have consistently shown high rates of thromboembolic complications associated with SVT, whether at first presentation or during follow-up. The CALISTO trial established for the first time the clinical benefit of a welldefined anticoagulant regimen for the prevention of serious thromboembolic complications in SVT patients, and we believe that patients such as those included in this trial should receive this regimen as tested. However, several areas of uncertainty remain for categories of SVT patients not evaluated in CALISTO.
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Management of Superficial Vein Thrombosis
La Revue du praticien, 2015Co-Authors: Paul Frappé, Nathalie Moulin, Laurent Bertoletti, Herve DecoususAbstract:Recent epidemiological studies have highlighted the potential severity of Superficial Vein Thrombosis of the lower limbs (SVT). Diagnosis is based on clinical and Doppler ultrasonography evaluation, and define its therapeutic management. If SVT is associated with objectively confirmed deep Vein Thrombosis or pulmonary embolism, curative anticoagulation is indicated. If SVT is isolated and measured over 5 cm long, prophylactic dosage of fondaparinux may be provided for 45 days.
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clinical relevance of symptomatic Superficial Vein Thrombosis extension lessons from the calisto study
Blood, 2013Co-Authors: Alain Leizorovicz, Francois Becker, A Buchmuller, I Quere, Paolo Prandoni, Herve DecoususAbstract:The clinical relevance of symptomatic extension of spontaneous, acute, symptomatic, lower-limb Superficial-Vein Thrombosis (SVT) is debated. We performed a post hoc analysis of a double-blind trial comparing fondaparinux with placebo. The main study outcome was SVT extension by day 77, whether to
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epidemiology diagnosis treatment and management of Superficial Vein Thrombosis of the legs
Best Practice & Research Clinical Haematology, 2012Co-Authors: Laurent Bertoletti, Herve Decousus, Paul Frappé, A Buchmuller, Sandrine Accassat, Benjamin Seffert, Adel MerahAbstract:Recent data on lower-limb Superficial-Vein Thrombosis (SVT) may substantially impact its clinical management. Particularly, the clear confirmation that SVT is closely linked to deep-Vein Thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE is diagnosed in 20–30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4–8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized, placebo-controlled CALISTO study. More recent data from another randomized trial support these findings. New recommendations on the management of SVT patients, including complete ultrasonography examination of the legs and, in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed, wherever the cost of fondaparinux is acceptable. Superficial-Vein Thrombosis (SVT) of the lower limbs has long been regarded as a benign, self-limiting disease, expected to resolve spontaneously and rapidly, and requiring only symptomatic treatments [1,2]. However, the perception of this disease is now changing with the recent publication of data indicating its potential severity [3] and showing for the first time the benefit of a therapeutic strategy based on the administration of an anticoagulant treatment [4]. The overall management of this frequent disease therefore needs to be reconsidered.
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Superficial Vein Thrombosis and recurrent venous thromboembolism a pooled analysis of two observational studies
Journal of Thrombosis and Haemostasis, 2012Co-Authors: Jeanphilippe Galanaud, Herve Decousus, I Quere, M A Sevestre, C Genty, Jeanluc Bosson, Emilie Presles, Michel Cucherat, Alain LeizoroviczAbstract:BACKGROUND: The management strategies for symptomatic isolated Superficial Vein Thrombosis (SVT) (without concomitant deep Vein Thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment. DESIGN AND METHODS: We performed a pooled analysis on individual data from two observational, multicenter, prospective studies, to determine predictors for VTE recurrence and their impact in an unselected population of symptomatic isolated SVT patients. RESULTS: One thousand and seventy-four cases of symptomatic isolated SVT were followed up at 3 months. VTE recurrence was observed in 3.9% of the patients; 16.2% of the patients did not receive anticoagulants, and 0.6% experienced a VTE recurrence. Cancer, personal history of VTE and saphenofemoral/popliteal involvement significantly increased the risk of subsequent VTE or DVT/PE in univariate analyses. Only male sex significantly increased the risk of VTE or DVT/PE recurrence in multivariate analyses. Twelve percent of the patients had cancer or saphenofemoral junction involvement, and were at higher risk of DVT/PE recurrence than patients without those characteristics (4.7% vs. 1.9%, P= 0.06). CONCLUSIONS: In patients with symptomatic SVT, only male sex significantly and independently increased the risk of VTE recurrence. Cancer or saphenofemoral junction involvement defined a population at high risk for deep VTE recurrence. Some SVTs might be safely managed without anticoagulants.
Paolo Prandoni - One of the best experts on this subject based on the ideXlab platform.
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clinical relevance of symptomatic Superficial Vein Thrombosis extension lessons from the calisto study
Blood, 2013Co-Authors: Alain Leizorovicz, Francois Becker, A Buchmuller, I Quere, Paolo Prandoni, Herve DecoususAbstract:The clinical relevance of symptomatic extension of spontaneous, acute, symptomatic, lower-limb Superficial-Vein Thrombosis (SVT) is debated. We performed a post hoc analysis of a double-blind trial comparing fondaparinux with placebo. The main study outcome was SVT extension by day 77, whether to
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fondaparinux reduces all types of symptomatic thromboembolic complications in patients with Superficial Vein Thrombosis in the legs data from the calisto study
Blood, 2011Co-Authors: Alain Leizorovicz, Paolo Prandoni, Herve DecoususAbstract:Abstract 2310 on behalf of the Steering Committee of the CALISTO Study. Background The CALISTO trial demonstrated the clinical benefit of anticoagulant therapy in patients with spontaneous isolated Superficial-Vein Thrombosis (SVT) in the legs (n=3002).1 Compared with placebo, a 45-day once-daily subcutaneous treatment with fondaparinux 2.5 mg was associated with a 85% relative reduction in the risk of the composite of all-cause death and adjudicated symptomatic thromboembolic complications at day 47, a benefit that was maintained at 30-day follow-up (day 77) and was not associated with an increased bleeding risk. The benefit of fondaparinux was observed with the same magnitude on each thromboembolic component of the primary efficacy outcome, including symptomatic extension of SVT to the sapheno-femoral junction (SFJ). However, although all symptomatic extensions of the index SVT were reported and reviewed, only those within 3 cm of the SFJ were counted for the primary outcome. To better characterize the efficacy of fondaparinux we used a new composite efficacy outcome, including all symptomatic extensions of SVT, regardless of their distance from the SFJ. Methods The composite thromboembolic outcome of the original primary endpoint of the CALISTO trial included symptomatic pulmonary embolism (PE), symptomatic deep-Vein Thrombosis (DVT), symptomatic extension of the index SVT to ≤3 cm (EXT ≤3 cm) from the SFJ, and symptomatic recurrence of SVT (composite outcome CO-1). In a post-hoc analysis, we additionally included in the composite outcome (CO-2) all symptomatic extensions of the index SVT regardless of their final distance from the SFJ (EXT >3 cm). All symptomatic thromboembolic events were confirmed by appropriate objective tests and reviewed by an independent, central, blinded adjudication committee. Results Overall, symptomatic EXT ≤3 cm and EXT >3 cm of index SVT at day 77 were reported in 59 (2.0%) and 68 patients (2.3%), respectively. Compared with placebo, fondaparinux significantly reduced at day 77 both the rate of CO-1, from 6.2% (93/1500) to 1.1% (17/1502; RR, 0.18, 95% confidence interval [CI], 0.11 to 0.31, p 3 cm from 3.7% (56/1500) to 0.8% (12/1501; RR, 0.21, 95% CI, 0.12 to 0.40, p 3 cm also experienced symptomatic PE or DVT during the course of the trial. In the fondaparinux group, none of the patients with SVT extension, reaching ≤3 cm or >3 cm from the SFJ, experienced symptomatic PE or DVT. Fondaparinux was associated with less use of medical resources, particularly in terms of surgery to treat SVT or need for anticoagulant therapy (Table). Conclusion Extension of the index SVT is a clinically relevant complication of the disease, regardless of the distance of the extension from the SFJ, and is associated with additional use of medical resources. Compared with placebo, fondaparinux reduced the rate of symptomatic thromboembolic complications in patients with spontaneous isolated SVT in the legs. 1Decousus H, et al; CALISTO Study Group. N Engl J Med 2010;363:1222-32. Disclosures: Leizorovicz:BMS: Research Funding; Sanofi Aventis: Honoraria; Bayer: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria. Off Label Use: Fondaparinux for the treatment of Superficial Vein Thrombosis, labelled in Europe. Prandoni:GSK: Membership on an entity9s Board of Directors or advisory committees. Decousus:GSK: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Membership on an entity9s Board of Directors or advisory committees.
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the risk of subsequent cancer and arterial cardiovascular events in patients with Superficial Vein Thrombosis in the legs
Blood, 2011Co-Authors: Paolo Prandoni, Alain Leizorovicz, Edoardo Casiglia, Valerie Tikhonoff, Herve DecoususAbstract:Although it has been clearly demonstrated that venous thromboembolism is associated with an increased risk of subsequent overt cancer and arterial cardiovascular events in comparison with control populations, whether this association also applies to patients with isolated (ie, without concomitant involvement of the deep Vein system) Superficial Vein Thrombosis (SVT) in the legs is unknown. In 737 consecutive patients with isolated SVT not involving the sapheno-femoral junction, we conducted a retrospective investigation to assess the rate of cancer and that of arterial cardiovascular events occurring during follow-up. The event rates were compared with those occurring in 1438 controls having comparable characteristics. Both cases and controls were followed-up for an average period of 26 ± 8 months (range, 3-45). Malignancy was diagnosed in 26 cases (3.5%) and 56 controls (3.9%), leading to a hazard ratio of 0.86 (95% confidence interval, 0.55%-1.35%). Arterial cardiovascular events occurred in 32 cases (4.3%) and 63 controls (4.4%), leading to a hazard ratio of 0.97 (95% confidence interval, 0.63%-1.50%). We conclude that the occurrence of isolated SVT in the legs does not place patients at an increased risk of malignancies or arterial cardiovascular events. Whether this conclusion also applies to patients whose Thrombosis involves the sapheno-femoral junction remains to be demonstrated.
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Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs
The New England Journal of Medicine, 2010Co-Authors: Herve Decousus, Silvy Laporte, Patrick Mismetti, Paolo Prandoni, Rupert Bauersachs, Z Boda, Benjamin Brenner, Lajos Matyas, Saskia Middeldorp, German SokurenkoAbstract:Results The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fonda parinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P
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fondaparinux for the treatment of Superficial Vein Thrombosis in the legs
The New England Journal of Medicine, 2010Co-Authors: Herve Decousus, Silvy Laporte, Patrick Mismetti, Paolo Prandoni, Rupert Bauersachs, Z Boda, Benjamin Brenner, Lajos Matyas, Saskia Middeldorp, German SokurenkoAbstract:Results The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fonda parinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-Vein Thrombosis was 85% lower in the fondaparinux group than in the pla cebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-Vein Thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo. Conclusions Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treat ment of patients with acute, symptomatic Superficial-Vein Thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials .gov number, NCT00443053.)
Alain Leizorovicz - One of the best experts on this subject based on the ideXlab platform.
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annual diagnosis rate of Superficial Vein Thrombosis of the lower limbs the steph community based study
Journal of Thrombosis and Haemostasis, 2014Co-Authors: Laurent Bertoletti, Paul Frappé, Alain Leizorovicz, Andrea Buchmullercordier, C Bonithonkopp, S Couzan, P Lafond, Adel MerahAbstract:Summary Background The incidence of Superficial Vein Thrombosis (SVT) in the general adult population remains unknown. Objectives To assess the annual diagnosis rate of symptomatic, objectively confirmed lower limb SVT, associated or not with concomitant deep Vein Thrombosis and/or symptomatic pulmonary embolism. Methods/patients We conducted, from November 14, 2011, to November 13, 2012, a multicenter, community-based study in the Saint-Etienne urban area, France, representing a population of 265 687 adult residents (according to the 2009 census). All 248 general practitioners located within the area were asked to refer any patient with clinically suspected lower limb acute SVT to a vascular physician for systematic compression ultrasonography. All 28 vascular physicians located within the area participated in the study. The annual diagnosis rate, with the corresponding 95% confidence interval (CI), was calculated as the number of patients with symptomatic, objectively confirmed SVT divided by the number of person-years at risk defined by population data of the area. All venous thromboembolic events were validated by an independent central adjudication committee. Results Overall, 171 patients with symptomatic, confirmed SVT were reported. The annual diagnosis rate was 0.64% (95% CI, 0.55%–0.74%), was higher in women, and increased with advancing age regardless of gender. Concomitant deep Vein Thrombosis (20 proximal) was observed in 42 patients (24.6% [95% CI, 18.3%–31.7%]), and concomitant symptomatic pulmonary embolism was observed in eight patients (4.7% [95% CI, 2.0%–9.0%]). Conclusions This first community-based study showed that symptomatic SVT with confirmed diagnosis is a relatively common disease frequently associated with thromboembolic events in the deep venous system.
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clinical relevance of symptomatic Superficial Vein Thrombosis extension lessons from the calisto study
Blood, 2013Co-Authors: Alain Leizorovicz, Francois Becker, A Buchmuller, I Quere, Paolo Prandoni, Herve DecoususAbstract:The clinical relevance of symptomatic extension of spontaneous, acute, symptomatic, lower-limb Superficial-Vein Thrombosis (SVT) is debated. We performed a post hoc analysis of a double-blind trial comparing fondaparinux with placebo. The main study outcome was SVT extension by day 77, whether to
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Superficial Vein Thrombosis and recurrent venous thromboembolism a pooled analysis of two observational studies
Journal of Thrombosis and Haemostasis, 2012Co-Authors: Jeanphilippe Galanaud, Herve Decousus, I Quere, M A Sevestre, C Genty, Jeanluc Bosson, Emilie Presles, Michel Cucherat, Alain LeizoroviczAbstract:BACKGROUND: The management strategies for symptomatic isolated Superficial Vein Thrombosis (SVT) (without concomitant deep Vein Thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment. DESIGN AND METHODS: We performed a pooled analysis on individual data from two observational, multicenter, prospective studies, to determine predictors for VTE recurrence and their impact in an unselected population of symptomatic isolated SVT patients. RESULTS: One thousand and seventy-four cases of symptomatic isolated SVT were followed up at 3 months. VTE recurrence was observed in 3.9% of the patients; 16.2% of the patients did not receive anticoagulants, and 0.6% experienced a VTE recurrence. Cancer, personal history of VTE and saphenofemoral/popliteal involvement significantly increased the risk of subsequent VTE or DVT/PE in univariate analyses. Only male sex significantly increased the risk of VTE or DVT/PE recurrence in multivariate analyses. Twelve percent of the patients had cancer or saphenofemoral junction involvement, and were at higher risk of DVT/PE recurrence than patients without those characteristics (4.7% vs. 1.9%, P= 0.06). CONCLUSIONS: In patients with symptomatic SVT, only male sex significantly and independently increased the risk of VTE recurrence. Cancer or saphenofemoral junction involvement defined a population at high risk for deep VTE recurrence. Some SVTs might be safely managed without anticoagulants.
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value of a planned compression ultrasonography after an isolated Superficial Vein Thrombosis results from a prospective multicentre study
European Journal of Vascular and Endovascular Surgery, 2012Co-Authors: Sara Quenet, Laurent Bertoletti, Herve Decousus, Francois Becker, I Quere, J P Laroche, Alain LeizoroviczAbstract:Abstract Objectives To assess the efficiency of a systematically planned compression ultrasonography (SP-CUS) to detect venous thrombotic complications (VTCs) in patients with symptomatic isolated Superficial Vein Thrombosis (SVT). Design Post hoc analysis of a prospective, multicentre, cohort study (POST). Patients As many as 537 patients with CUS-confirmed isolated SVT undergoing an SP-CUS 8–15 days after the initial CUS. Outcomes Asymptomatic VTC (extension or recurrence of SVT, deep-Vein Thrombosis (DVT) of the lower limbs) diagnosed by the SP-CUS and symptomatic thromboembolic complications (VTC and pulmonary embolism (PE)) up to 3 months. Results VTC was suspected before or on the day of the SP-CUS in 18 patients (3.0%). Among the 519 asymptomatic patients (97%) undergoing SP-CUS, this revealed asymptomatic VTC in 12 patients (2.3%; 4 DVT, 4 SVT recurrences, 4 SVT extensions), none of whom subsequently experienced symptomatic thromboembolic events up to 3 months. Among the 507 patients with a normal SP-CUS, 29 (5.7%) presented symptomatic thromboembolic events during follow-up: 2 PE, 7 DVT, 9 SVT recurrences and 11 SVT extensions. Conclusions In this study, the SP-CUS detected a few asymptomatic VTC, but failed to identify patients at risk of thromboembolic events during follow-up. Use of an SP-CUS was therefore neither efficient nor cost effective.
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fondaparinux reduces all types of symptomatic thromboembolic complications in patients with Superficial Vein Thrombosis in the legs data from the calisto study
Blood, 2011Co-Authors: Alain Leizorovicz, Paolo Prandoni, Herve DecoususAbstract:Abstract 2310 on behalf of the Steering Committee of the CALISTO Study. Background The CALISTO trial demonstrated the clinical benefit of anticoagulant therapy in patients with spontaneous isolated Superficial-Vein Thrombosis (SVT) in the legs (n=3002).1 Compared with placebo, a 45-day once-daily subcutaneous treatment with fondaparinux 2.5 mg was associated with a 85% relative reduction in the risk of the composite of all-cause death and adjudicated symptomatic thromboembolic complications at day 47, a benefit that was maintained at 30-day follow-up (day 77) and was not associated with an increased bleeding risk. The benefit of fondaparinux was observed with the same magnitude on each thromboembolic component of the primary efficacy outcome, including symptomatic extension of SVT to the sapheno-femoral junction (SFJ). However, although all symptomatic extensions of the index SVT were reported and reviewed, only those within 3 cm of the SFJ were counted for the primary outcome. To better characterize the efficacy of fondaparinux we used a new composite efficacy outcome, including all symptomatic extensions of SVT, regardless of their distance from the SFJ. Methods The composite thromboembolic outcome of the original primary endpoint of the CALISTO trial included symptomatic pulmonary embolism (PE), symptomatic deep-Vein Thrombosis (DVT), symptomatic extension of the index SVT to ≤3 cm (EXT ≤3 cm) from the SFJ, and symptomatic recurrence of SVT (composite outcome CO-1). In a post-hoc analysis, we additionally included in the composite outcome (CO-2) all symptomatic extensions of the index SVT regardless of their final distance from the SFJ (EXT >3 cm). All symptomatic thromboembolic events were confirmed by appropriate objective tests and reviewed by an independent, central, blinded adjudication committee. Results Overall, symptomatic EXT ≤3 cm and EXT >3 cm of index SVT at day 77 were reported in 59 (2.0%) and 68 patients (2.3%), respectively. Compared with placebo, fondaparinux significantly reduced at day 77 both the rate of CO-1, from 6.2% (93/1500) to 1.1% (17/1502; RR, 0.18, 95% confidence interval [CI], 0.11 to 0.31, p 3 cm from 3.7% (56/1500) to 0.8% (12/1501; RR, 0.21, 95% CI, 0.12 to 0.40, p 3 cm also experienced symptomatic PE or DVT during the course of the trial. In the fondaparinux group, none of the patients with SVT extension, reaching ≤3 cm or >3 cm from the SFJ, experienced symptomatic PE or DVT. Fondaparinux was associated with less use of medical resources, particularly in terms of surgery to treat SVT or need for anticoagulant therapy (Table). Conclusion Extension of the index SVT is a clinically relevant complication of the disease, regardless of the distance of the extension from the SFJ, and is associated with additional use of medical resources. Compared with placebo, fondaparinux reduced the rate of symptomatic thromboembolic complications in patients with spontaneous isolated SVT in the legs. 1Decousus H, et al; CALISTO Study Group. N Engl J Med 2010;363:1222-32. Disclosures: Leizorovicz:BMS: Research Funding; Sanofi Aventis: Honoraria; Bayer: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria. Off Label Use: Fondaparinux for the treatment of Superficial Vein Thrombosis, labelled in Europe. Prandoni:GSK: Membership on an entity9s Board of Directors or advisory committees. Decousus:GSK: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Membership on an entity9s Board of Directors or advisory committees.
Jan Beyerwestendorf - One of the best experts on this subject based on the ideXlab platform.
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controversies in venous thromboembolism to treat or not to treat Superficial Vein Thrombosis
Hematology, 2017Co-Authors: Jan BeyerwestendorfAbstract:: The management of Superficial Vein Thrombosis (SVT) is poorly defined and remains controversial overall. SVT has long been considered a benign, self-limited disease, but recent studies show that SVT carries a nonnegligible risk for recurrence, deep Vein Thrombosis, or pulmonary embolism. Current guidelines recommend the use of low-molecular-weight heparin or fondaparinux, but results of several surveys indicate that the majority of patients with SVT receive nonanticoagulant therapy only, which includes compression stockings or bandages, nonsteroidal anti-inflammatory drugs, topical application of heparin gel, or surgical interventions. However, several recent observational and interventional studies provide better insight into the optimal treatment of patients with SVT who are at different risks for thromboembolic complications. This educational review summarizes the available evidence and aims to provide practical guidance based on a clinical decision pathway.
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prevention of thromboembolic complications in patients with Superficial Vein Thrombosis given rivaroxaban or fondaparinux the open label randomised non inferiority surprise phase 3b trial
The Lancet Haematology, 2017Co-Authors: Jan Beyerwestendorf, Sebastian Schellong, Horst E Gerlach, Eberhard Rabe, Jeffrey I Weitz, Katja Jersemann, Kurtulus Sahin, Rupert BauersachsAbstract:Summary Background Superficial-Vein Thrombosis can lead to deep-Vein Thrombosis and pulmonary embolism. Rivaroxaban, an oral factor Xa inhibitor, might simplify treatment compared with fondaparinux because it does not require daily subcutaneous injection and is cheaper. We compared efficacy outcomes in patients with Superficial-Vein Thrombosis and additional risk factors given either rivaroxaban or fondaparinux to assess whether rivaroxaban is non-inferior to fondaparinux in the prevention of thromboembolic complications. Methods In this open-label, masked endpoint, randomised, non-inferiority phase 3b trial, we recruited patients aged 18 years or older with symptomatic Superficial-Vein Thrombosis from 27 sites (academic, community hospitals, and specialist practices) in Germany. We randomly assigned patients (1:1) to receive 10 mg oral rivaroxaban or 2·5 mg subcutaneous fondaparinux once a day for 45 days. Patients were eligible if they had symptomatic Thrombosis (at least 5 cm in a supragenual Superficial-Vein segment) and at least one additional risk factor (older than 65 years, male sex, previous venous thromboembolism, cancer, autoimmune disease, Thrombosis of non-varicose Veins). Main exclusion criteria were: symptoms for longer than 3 weeks, thrombus within 3 cm of the sapheno-femoral junction, indication for full-dose anticoagulation therapy, and substantial hepatic or renal impairment. Randomisation was done with a central block randomisation process. The primary efficacy outcome was a composite of symptomatic deep-Vein Thrombosis or pulmonary embolism, progression or recurrence of Superficial Vein-Thrombosis, and all-cause mortality at 45 days in the per-protocol population (all randomly assigned patients without major protocol violations). We used a non-inferiority margin of 4·5% (absolute difference between rivaroxaban and fondaparinux). The main safety outcome was major bleeding. This study is registered with ClinicalTrials.gov, number NCT01499953. Findings Between April 25, 2012, and Feb 18, 2016, 485 patients were enrolled in the study and 472 were randomly assigned to the rivaroxaban group (n=236) or the fondaparinux group (n=236). In the 435 patients included in the per-protocol analysis set, the primary efficacy outcome occurred in seven (3%) of 211 patients (95% CI 1·6–6·7) in the rivaroxaban group and in four (2%) of 224 patients (0·7–4·5) in the fondaparinux group (hazard ratio [HR] 1·9, 95% CI 0·6–6·4; p=0·0025 for non-inferiority) at day 45. There were no major bleeds in either group. There was one death in the rivaroxaban group; this patient died from cardiogenic shock on day 50 after a type A aortic dissection, not related to treatment. Interpretation Rivaroxaban was non-inferior to fondaparinux for treatment of Superficial-Vein Thrombosis in terms of symptomatic deep-Vein Thrombosis or pulmonary embolism, progression or recurrence of Superficial Vein-Thrombosis, and all-cause mortality, and was not associated with more major bleeding. Therefore, rivaroxaban could offer patients with symptomatic Superficial-Vein Thrombosis a less burdensome and less expensive oral treatment option instead of a more expensive subcutaneous injection. Funding GWT-TUD and Bayer Vital.
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rivaroxaban versus fondaparinux in the treatment of Superficial Vein Thrombosis the surprise trial
Blood, 2016Co-Authors: Jan Beyerwestendorf, Sebastian Schellong, Horst E Gerlach, Katja Jersemann, Kurtulus Sahin, E Rabe, Rupert BauersachsAbstract:Background The current standard of therapy in Superficial Vein Thrombosis (SVT) comprises subcutaneous injections of the indirect factorXainhibitorfondaparinuxfor up to 45 days, which was highlyeffectivecompared to placebo in the CALISTO trial. However,fondaparinuxis expensive, requires daily injections and cost-effectiveness in SVT therapy has been questioned. Rivaroxaban is a direct oral factorXainhibitor which has been shown to be effective in the prevention and treatment of venous thromboembolism (VTE). We hypothesizedthat SVT patientsat high risk for VTE complications may be treated as efficacious and safe with rivaroxaban as withfondaparinux. Methods The SURPRISE trial, a randomized, open-label blinded outcome event adjudication trial, compared rivaroxaban 10 mg once daily withfondaparinux2.5 mg once daily in patients with SVT at high risk of VTE complications (defined assupragenualSVT + age > 65 years, male sex, previous VTE, cancer, autoimmune disease or SVT of non-varicose Veins). Treatment duration for both treatments was 45+5 days with an observational period until day 90+10. The primary efficacy outcome was a composite endpoint of deep Vein Thrombosis, pulmonary embolism, SVT progression towards thesaphenofemoraljunction, SVT recurrence or all cause death in the per-protocol analysis at day 45. A predefined sensitivity analysis was performed in all randomized patients (full analysis set). The primary safety outcome was the rate of ISTH major bleeding during treatment. Further outcome measures included the composite efficacy outcome up to day 90, each component of the primary efficacy outcome, rates of surgical treatment of SVT and rates of major VTE (composite of symptomatic PE or symptomatic proximal DVT or VTE-related death) at days 45 and 90. The trial was designed to test for non-inferiority of rivaroxaban compared tofondaparinuxwith respect to the primary efficacy outcome and to the rates of ISTH major bleeding. Results A total of 472 patients were randomized (mean age 60.3 years; 60.4% female) and treated with rivaroxaban (n=236) orfondaparinux(n=236). Mean treatment duration was 44.0 days for rivaroxaban and 44.8 days forfondaparinux. Until day 45+5, the primary efficacy outcome (n=435 in per-protocol analysis set) occurred in 3.3% (95%-CI 0.90; 5.73) of patients treated with rivaroxaban and 1.8% (95%-CI 0.05; 3.52) of patients receivingfondaparinux(absolute difference between rivaroxaban andfondaparinuxwas 1.53%; one-sided upper CI limit 4.03%; p-value for non-inferiority 0.025; table 1 and figure 1). Until day 90+10, the respective rates were 7.1% for rivaroxaban and 6.7% forfondaparinux(absolute difference 0.41;one-sided upper CI limit 4.41%;p-value for non-inferiority 0.047). Non-inferiority of rivaroxaban vs.fondaparinuxwas preserved in the full analysis set. No major bleeding occurred and rates of non-major, clinically relevant bleeding were 2.5 vs. 0.4% for day 45+5 and 2.5 vs. 0.9% for day 90+10 in safety set for rivaroxaban andfondaparinux, respectively (table 1).Mean±SDadherence (pill/syringe count at day 45) was 98.9±13.4% for rivaroxaban and 99.3±6.2% forfondaparinux(full analysis set). Conclusions In high-risk SVT patients, rivaroxaban was non-inferior tofondaparinuxin preventing thromboembolic complications with comparable safety. VTE events were predominantly SVT recurrence. Few cases of DVT and PE occurred, which indicates that a 45 days course of rivaroxaban 10 mg orfondaparinux2.5 mg is sufficient to prevent serious complications in this specific subset of SVT patients. As to whether oral rivaroxaban offers a better quality of life compared to 45 days of injections, this has to be investigated in future studies. We found higher SVT complications rates in both treatment arms compared to thefondaparinuxarm in the CALISTO trial. Therefore, patients at higher VTE risk can be identified by use of a simple risk factor assessment, which may help to improve cost-effectiveness of SVT therapy. However, the concept of SVT risk stratification needs to be further investigated, since patients without additional risk factors may not need anticoagulant therapy at all. (Funded by Bayer Vital GmbH, Germany, ClinicalTrials.gov NCT01499953) In response to a pre-submission enquiry, the New England Journal of Medicine indicated potential interest in the study results and a simultaneous publication/presentation is targeted. Disclosures Beyer-Westendorf: Daichii Sankyo: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; LEO: Consultancy, Honoraria, Research Funding. Schellong: Bayer: Honoraria; Pfizer: Honoraria; Boehringer-Ingelheim: Honoraria; Daichii Sankyo: Honoraria; LeoPharma: Honoraria. Gerlach: ASPEN: Honoraria; Bayer: Honoraria; Boehringer-Ingelheim: Honoraria; LeoPharma.: Honoraria. Rabe: Bayer: Honoraria; Boehringer Ingelheim: Honoraria; Daichii-Sankyo: Honoraria; LeoPharma: Honoraria; Pfizer: Honoraria. Bauersachs: Bayer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; BristolMyers Squibb: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; ASPEN: Honoraria, Research Funding.
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Superficial Vein Thrombosis treated for 45 days with rivaroxaban versus fondaparinux rationale and design of the surprise trial
Journal of Thrombosis and Thrombolysis, 2016Co-Authors: Sebastian Werth, Jan Beyerwestendorf, Sebastian Schellong, Horst E Gerlach, Rupert Bauersachs, E RabeAbstract:Patients with Superficial Vein Thrombosis (SVT) are commonly treated with low-molecular weight heparin or fondaparinux in prophylactic, intermediate or therapeutic dosages for treatment periods of 10-45 days. This practice is also reflected by the current guideline recommendations. However, given the broad range of thromboembolic complication rates in SVT (between 0 and 30 % have been reported) it seems reasonable to suspect that risk stratification is needed to differentiate patients at low risk who may not benefit from anticoagulation from those at high risk who may need higher dosages or a longer duration of anticoagulation. Furthermore, prolonged treatment with injectable anticoagulants has been shown to result in poor patient adherence. Direct oral anticoagulants have recently been approved for venous thromboembolism therapy and these new drugs may offer advantages also for SVT patients. The prospective, randomized, open-label, blinded adjudication trial Superficial phlebitis treated for 45 days with rivaroxaban versus fondaparinux (SURPRISE) will evaluate the efficacy and safety of 10 mg rivaroxaban OD compared to fondaparinux 2.5 mg OD for SVT treatment in a subset of high-risk SVT patients over a treatment period of 45 days. The purpose of the study is to demonstrate non-inferiority of rivaroxaban compared to fondaparinux in preventing the combined efficacy endpoint of thrombus progression, SVT recurrence, DVT, PE and death. The results of the SURPRISE trial will provide evidence for the concept of risk stratification in SVT and for the value of rivaroxaban 10 mg in SVT treatment (clinicaltrials.gov NCT01499953).
Benilde Cosmi - One of the best experts on this subject based on the ideXlab platform.
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the incidence of heparin induced thrombocytopenia in patients treated with low molecular weight heparin for Superficial Vein Thrombosis
Thrombosis Research, 2016Co-Authors: Michelangelo Sartori, Cristina Legnani, Elisabetta Favaretto, Gualtiero Palareti, Ludovica Migliaccio, G Guazzaloca, Benilde CosmiAbstract:Abstract Background The risk of heparin induced thrombocytopenia (HIT) associated with low molecular weight heparin (LMWH) for treatment of Superficial Vein Thrombosis (SVT) is uncertain. As a result the necessity of platelet count monitoring is unclear in this setting. Aims To assess the risk of HIT in outpatients treated with LMWH for SVT. Methods In a prospective single centre study we included all symptomatic outpatients in whom a real-time B-mode and color Doppler ultrasonography examination revealed SVT without DVT. Patients treated with vitamin K antagonists or fondaparinux were excluded. Patients received full dose enoxaparin for 1 week followed by half therapeutic dose for 3 weeks or parnaparin 8500 UI aXa for 10 days followed by 6400 UI aXa once daily for 20 days. Platelet count was performed on the day of diagnosis (D0) and 7 (D7), and 14 (D14) days afterward. Primary outcomes were the rate of thromboembolic events and of HIT during a 3-month follow-up. Results 678 outpatients (age: 64.7 ± 16.2 years, male: 42.0%) were evaluated. During follow-up, 7 venous thrombo-embolic events were recorded (1.03% CI 95%: 0.50–2.11%), while no major bleeding was observed (0.0% CI 95%: 0.0–0.56%). Platelet count was 255 ± 93 × 109/L at D0, 245 ± 93 × 109/L at D7 (p = 0.204 vs. D0) and 261 ± 116 × 109/L at D14 (p = 0.405 vs. D0). No fall in platelet count > 50% and no case of HIT were recorded (HR 0.0% CI 95%: 0–0.56%). Conclusions A 4-week LMWH treatment for SVT is associated with an incidence of HIT lower than 0.6% and platelet count monitoring may be omitted in this setting.
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management of Superficial Vein Thrombosis
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Benilde CosmiAbstract:Summary Superficial Vein Thrombosis (SVT) is less well studied than deep Vein Thrombosis (DVT), because it has been considered to be a minor, self-limiting disease that is easily diagnosed on clinical grounds and that requires only symptomatic relief. The most frequently involved sites of the Superficial Vein system are the lower limbs, especially the saphenous Veins, mostly in relation to varicosities. Lower-limb SVT shares the same risk factors as DVT; it can propagate into the deep Veins, and have a complicated course with pulmonary embolism. Clinical diagnosis may not be accurate, and ultrasonography is currently indicated for both confirmation and evaluation of SVT extension. Treatment aims are symptom relief and prevention of venous thromboembolism (VTE) in relation to the thrombotic burden. SVT of the long saphenous Vein within 3 cm of the saphenofemoral junction (SFJ) is considered to be equivalent to a DVT, and thus deserving of therapeutic anticoagulation. Less severe forms of lower-limb SVT not involving the SFJ have been included in randomized clinical trials of surgery, compression hosiery, non-steroidal anti-inflammatory drugs, unfractionated heparin, and low molecular weight heparins, with inconclusive results. The largest randomized clinical trial available, on 3004 patients with lower-limb SVT not involving the SFJ, showed that fondaparinux 2.5 mg once daily for 6 weeks is more effective than placebo in reducing the risk of the composite of death from any cause and symptomatic VTE (0.9% versus 5.9%). Further studies are needed to define the optimal management strategies for SVT of the lower limbs and other sites, such as the upper limbs.
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inherited and acquired thrombophilic alterations in patients with Superficial Vein Thrombosis of lower limbs
Thrombosis and Haemostasis, 2014Co-Authors: Cristina Legnani, Michela Cini, Benilde Cosmi, Massino Filippini, Elisabetta Favaretto, Gualtiero PalaretiAbstract:Inherited and acquired thrombophilic alterations in patients with Superficial Vein Thrombosis of lower limbs -
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risk factors for recurrent events in subjects with Superficial Vein Thrombosis in the randomized clinical trial steflux Superficial thromboembolism fluxum
Thrombosis Research, 2014Co-Authors: Benilde Cosmi, Cristina Legnani, Massimo Filippini, Giampiero Avruscio, Angelo Ghirarduzzi, Eugenio Bucherini, Giuseppe Camporese, Davide Imberti, Fausto Campana, Gualtiero PalaretiAbstract:Abstract Background/Aims To evaluate risk factors for recurrent events in patients enrolled in the SteFlux (Superficial Thromboembolism Fluxum) clinical trial which compared different doses and duration of low molecular weight heparin (parnaparin) for Superficial Vein Thrombosis (SVT). Materials and Methods Outpatients with acute SVT of at least 4 cm in length of the internal or external saphenous Veins or their collaterals were randomized in a double blind fashion to receive either parnaparin 8500 UI aXa od for ten days followed by placebo for 20 days or 8500 UI aXa od for ten days followed by 6400 UI aXa od for 20 days or 4250 UI aXa od for 30 days. Outcomes were the composite of symptomatic and asymptomatic deep Vein Thrombosis, pulmonary embolism and SVT recurrence or extension in the first 30 +/− 3 days with a 60 +/− 3 day follow-up. Results 98 outcomes (14.7%) were recorded during 93 days among 664 patients (M/F: 246/418, mean age 65). After correction for treatment, outcomes during 33 days were associated with previous venous thromboembolism (VTE) and/or SVT and/or family history of VTE (odds ratio-OR: 2.5; 95% confidence interval - CI: 1.4-4.8; p = 0.003). After stopping LMWH treatment, only the absence of varicose Veins (OR: 2.5; 95% CI 1.3-5.0; p = 0.004) and previous VTE and/or SVT and/or family history of VTE (OR: 1.9; 95% CI:1.0-3.7; p = 0.048) were significantly associated with outcomes. Conclusions SVT patients with these factors may deserve a higher intensity and/or longer anticoagulant treatment.
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a randomized double blind study of low molecular weight heparin parnaparin for Superficial Vein Thrombosis steflux Superficial thromboembolism and fluxum
Journal of Thrombosis and Haemostasis, 2012Co-Authors: Benilde Cosmi, Massimo Filippini, D. Tonti, Giampiero Avruscio, Angelo Ghirarduzzi, Eugenio Bucherini, Giuseppe Camporese, Davide Imberti, G. PalaretiAbstract:BACKGROUND: Optimal doses and duration of low-molecular-weight heparin (LMWH) for the treatment of Superficial Vein Thrombosis (SVT) are still uncertain. OBJECTIVES: To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT. PATIENTS AND METHODS: Outpatients with at least a 4-cm-long SVT of long or short saphenous Veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double-blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep Vein Thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow-up. RESULTS: Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8-18.9 P<0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6-9.4 P= 0.011; C vs. A: ARR: 8.2%, 95% CI: 2-14 P=0.012). During days 0-93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P=0.001) or C (14.3%, P=0.034). No major hemorrhages occurred. CONCLUSIONS: An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment.