Vitamin K Antagonists After 6 Months of Low-Molecular-Weight Heparin in Cancer Patients with Venous Thromboembolism.

Low-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond 6 months remain scanty. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate of venous thromboembolism recurrences and major bleeding appearing beyond the first 6 months of anticoagulant therapy in cancer patients with venous thromboembolism, according to therapy with LMWH or vitamin K antagonists (VKA). We performed a propensity score-matched cohort study. After propensity matching, 482 cancer patients continued to receive LMWH and 482 switched to VKA. During the course of anticoagulant therapy (mean 275.5 days), 57 patients developed venous thrombosis recurrences (recurrent pulmonary embolism 26, recurrent deep vein thrombosis 29, both 2), 28 had major bleeding, 38 had nonmajor bleeding, and 129 died. No patient died of recurrent venous thrombosis, and 5 patients died of bleeding (2 were on LMWH, 3 on VKA). Patients who continued with LMWH had a similar rate of deep vein thrombosis recurrences (relative risk [RR] 1.41; 95% confidence interval [CI], 0.68-2.93), pulmonary embolism recurrences (RR 0.73; 95% CI, 0.34-1.58), major bleeding (RR 0.96; 95% CI, 0.51-1.79), or nonmajor bleeding (RR 1.15; 95% CI, 0.55-2.40), compared with those who switched to VKA, but a higher mortality rate (RR 1.58; 95% CI, 1.13-2.20). In cancer patients with venous thromboembolism who completed 6 months of LMWH therapy, switching to VKA was associated with a similar risk of venous thrombosis recurrences or bleeding when compared with patients who continued LMWH.

Chai-Adisaksopha C ，Iorio A ，Crowther MA ，de Miguel J ，Salgado E ，Zdraveska M ，Fernández-Capitán C ，Nieto JA ，Barillari G ，Bertoletti L ，Monreal M ，RIETE investigators ... -  《-》

Long-term use of different doses of low-molecular-weight heparin versus vitamin K antagonists in the treatment of venous thromboembolism.

We evaluated whether the incidence of recurrent venous thromboembolic events (VTEs) during and after therapy differs for patients treated with full or reduced doses of low-molecular-weight heparin (LMWH) used long term compared with vitamin K antagonists (VKAs). We identified randomized studies of long-term treatment with LMWH or VKA by searching MEDLINE, EMBASE, BIOSIS, and PASCAL. Seventeen studies were included, with 4,002 patients. In the assessment at 12 months of 1,957 patients without cancer, the recurrence rates of VTE in the LMWH/VKA groups were 8.3%/7.6% in the studies using full doses and 12.3%/12.1% in those using prophylactic doses. However, combined analysis after treatment to 1 year showed a nonsignificant (NS) trend to lower recurrent symptomatic VTE in favor of VKA (RR = 1.46, 95% CI 0.96-2.23). In 1,292 patients with cancer the recurrence rates of VTE in the LMWH/VKA groups were 6.5%/17.9% (p = 0.005) in the studies using full doses, 7.1%/13.4% (p = 0.002) in the studies using intermediate doses, and 14.3%/19.1% (p = NS) in the studies using prophylactic doses. Furthermore, the recurrences of VTE after discontinuation of treatment in the LMWH/VKA groups were 1.6%/9.5% (RR = 0.25, 95% CI 0.06-1.1) in 252 patients with full doses and 12%/7.4% (RR = 1.49, 95% CI 0.3-7.48) in 52 patients with prophylactic doses. In this population with cancer, the full-treatment LMWH regimen did not produce more major bleeding events than intermediate or prophylactic doses (5.1% vs. 6.3% or 8.1%, respectively). Full-dose LMWH for 3-6 months is as safe as intermediate and prophylactic doses for the long-term treatment of deep vein thrombosis. In patients with cancer it appears that there is an excess of VTE recurrence after treatment with prophylactic doses that does not occur with full therapeutic doses.

Romera-Villegas A ，Cairols-Castellote MA ，Vila-Coll R ，Martí-Mestre X ，Colomé E ，Iguaz I ... -  《-》

Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis.

Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.

Schulman S ，Zondag M ，Linkins L ，Pasca S ，Cheung YW ，de Sancho M ，Gallus A ，Lecumberri R ，Molnar S ，Ageno W ，Le Gal G ，Falanga A ，Hulegårdh E ，Ranta S ，Kamphuisen P ，Debourdeau P ，Rigamonti V ，Ortel TL ，Lee A ... -  《-》

Vitamin K antagonists versus low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.

Andras A ，Sala Tenna A ，Stewart M 《Cochrane Database of Systematic Reviews》

Venous thromboembolism in centenarians: Findings from the RIETE registry.

The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Lacruz B ，Tiberio G ，Núñez MJ ，López-Jiménez L ，Riera-Mestre A ，Tiraferri E ，Verhamme P ，Mazzolai L ，González J ，Monreal M ，RIETE Investigators ... -  《-》