Background Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K antagonists (VKAs) for venous thromboembolism (VTE) treatment, as shown via intention-to-treat comparative effectiveness analysis. However, on-treatment analysis is imperative in observational studies because anticoagulation choice and duration are at investigators' discretion. Objectives The aim of the study is to compare the effectiveness of DOACs and VKAs on 12-month outcomes in VTE patients using on-treatment analysis. Methods The Global Anticoagulant Registry in the FIELD - VTE (GARFIELD-VTE) is a world-wide, prospective, non-interventional study observing treatment of VTE in routine clinical practice. Results In total, 8,034 patients received VKAs ( n = 3,043, 37.9%) or DOACs ( n = 4,991, 62.1%). After adjustment for baseline characteristics and follow-up bleeding events, and accounting for possible time-varying confounding, all-cause mortality was significantly lower with DOACs than VKAs (hazard ratio: 0.58 [95% confidence interval 0.42-0.79]). Furthermore, patients receiving VKAs were more likely to die of VTE complications (4.9 vs. 2.2%) or bleeding (4.9 vs. 0.0%). There was no significant difference in rates of recurrent VTE (hazard ratio: 0.74 [0.55-1.01]), major bleeding (hazard ratio: 0.76 [0.47-1.24]), or overall bleeding (hazard ratio: 0.87 [0.72-1.05]) with DOACs or VKAs. Unadjusted analyses suggested that VKA patients with active cancer or renal insufficiency were more likely to die than patients treated with DOAC (52.51 [37.33-73.86] vs. 26.52 [19.37-36.29] and 9.97 [7.51-13.23] vs. 4.70 [3.25-6.81] per 100 person-years, respectively). Conclusion DOACs and VKAs had similar rates of recurrent VTE and major bleeding. However, DOACs were associated with reduced all-cause mortality and a lower likelihood of death from VTE or bleeding compared with VKAs.

• Klíčová slova
• anticoagulation, direct oral anticoagulants, on-treatment comparative effectiveness, venous thromboembolism, vitamin K antagonists,
• Publikační typ
• časopisecké články MeSH

The decision on treatment after a first venous thromboembolism (VTE) to prevent recurrences may be influenced by many factors. The prospective, observational, WHITE study aimed to analyze how this issue was tackled in every-day clinical practice in various countries, which have sensibly different socio-economic conditions and healthcare systems. Doctors active in 79 Internal or Vascular clinical centers in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia) enrolled VTE patients after the maintenance treatment phase. The present report analyzed information, collected in the central database, regarding the baseline characteristics, index events, type and duration of anticoagulant therapy and decision on post-maintenance treatment. From April 2018 to December 2020, 1240 patients were enrolled, 58% with an unprovoked index event. Direct oral anticoagulants (DOACs) were used in > 85% of all cases in China, Poland, Portugal, Russia and Czechia, in 52% in Slovakia and in no patient in Tunisia. The maintenance anticoagulation lasted in average approximately 6 months. Altogether, anticoagulation was stopped in 20%, extended in about 50%, regardless of whether the event was unprovoked or provoked and shifted to antithrombotics (mainly sulodexide or aspirin) in the remaining patients. In conclusion, some differences in VTE patient management were found between countries. The provoked/unprovoked nature of the index event, instead, was not the prevalent criterion to drive the decision on extension of anticoagulation, without large variations between countries. DOACs were the most widely used anticoagulant drugs, whereas > 25% of patients received antithrombotic drugs instead of anticoagulants as extended treatment.

• Klíčová slova
• Anticoagulants, Anticoagulation, Antithrombotics, Aspirin, Sulodexide, Venous thromboembolism,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• hemokoagulace MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• rizikové faktory MeSH
• žilní tromboembolie * farmakoterapie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antikoagulancia MeSH

This open-label, single-arm, prospective cohort trial is the first phase 3 safety study to describe outcomes in children treated with dabigatran etexilate for secondary venous thromboembolism (VTE) prevention. Eligible children aged 12 to <18 years (age stratum 1), 2 to <12 years (stratum 2), and >3 months to <2 years (stratum 3) had an objectively confirmed diagnosis of VTE treated with standard of care (SOC) for ≥3 months, or had completed dabigatran or SOC treatment in the DIVERSITY trial (NCT01895777) and had an unresolved clinical thrombosis risk factor requiring further anticoagulation. Children received dabigatran for up to 12 months, or less if the identified VTE clinical risk factor resolved. Primary end points included VTE recurrence, bleeding events, and mortality at 6 and 12 months. Overall, 203 children received dabigatran, with median exposure being 36.3 weeks (range, 0-57 weeks); 171 of 203 (84.2%) and 32 of 203 (15.8%) took capsules and pellets, respectively. Overall, 2 of 203 children (1.0%) experienced on-treatment VTE recurrence, and 3 of 203 (1.5%) experienced major bleeding events, with 2 (1.0%) reporting clinically relevant nonmajor bleeding events, and 37 (18.2%) minor bleeding events. There were no on-treatment deaths. On-treatment postthrombotic syndrome was reported for 2 of 162 children (1.2%) who had deep vein thrombosis or central-line thrombosis as their most recent VTE. Pharmacokinetic/pharmacodynamic relationships of dabigatran were similar to those in adult VTE patients. In summary, dabigatran showed a favorable safety profile for secondary VTE prevention in children aged from >3 months to <18 years with persistent VTE risk factor(s). This trial was registered at www.clinicaltrials.gov as #NCT02197416.

• MeSH
• časové faktory MeSH
• dabigatran škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dítě MeSH
• Kaplanův-Meierův odhad MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• rizikové faktory MeSH
• sekundární prevence * MeSH
• stanovení cílového parametru MeSH
• žilní tromboembolie farmakoterapie   prevence a kontrola   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dabigatran MeSH

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

• MeSH
• dospělí MeSH
• fibrinolytika aplikace a dávkování   terapeutické užití   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• myeloproliferativní poruchy komplikace   MeSH
• nádory kostní dřeně komplikace   MeSH
• plicní embolie farmakoterapie   etiologie   MeSH
• premedikace metody   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitamin K antagonisté a inhibitory   MeSH
• žilní tromboembolie farmakoterapie   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fibrinolytika MeSH
• vitamin K MeSH

BACKGROUND: Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions with a low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is not well known. METHODS AND RESULTS: In this multicenter, double-blind study, 615 patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment were randomly assigned to sulodexide 500 lipasemic units twice daily or placebo for 2 years, in addition to elastic stockings. The primary efficacy outcome was recurrence of venous thromboembolism. Major or clinically relevant bleeding was the primary safety outcome. Venous thromboembolism recurred in 15 of the 307 patients who received sulodexide and in 30 of the 308 patients who received placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.27-0.92; P=0.02). The analysis in which lost to follow-up was assigned to failure yielded a risk ratio among treated versus control subjects of 0.54 (95% confidence interval, 0.35-0.85; P=0.009). No major bleeding episodes occurred; 2 patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the 2 groups. CONCLUSION: Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked venous thromboembolism, with no apparent increase of bleeding risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77.

• Klíčová slova
• glycosaminoglycans, randomized controlled trial, recurrence, venous thromboembolism,
• MeSH
• antikoagulancia aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• glykosaminoglykany aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• recidiva MeSH
• rozvrh dávkování léků MeSH
• sekundární prevence metody   MeSH
• senioři MeSH
• žilní tromboembolie diagnóza   prevence a kontrola   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antikoagulancia MeSH
• glucuronyl glucosamine glycan sulfate MeSH Prohlížeč
• glykosaminoglykany MeSH