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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DIRECT ORAL ANTICOAGULANTS

Several direct oral anticoagulants (DOACs), namely, apixaban, rivaroxaban, and dabigatran etexilate, are currently licensed in Europe and the United States for various thromboembolic indications. They provide alternatives to low molecular weight heparin in a peri-operative setting for venous thromboembolism (VTE) prophylaxis and therapy and to vitamin K antagonists for longer term therapy. Routine coagulation monitoring is not required with DOACs but is recommended in patients with renal impairment, acute bleeding, overdoses, or emergency surgery. If bleeding is life-threatening, the offlabel therapeutic use of PCC or activated PCC may be considered in an attempt to reverse the anticoagulant effect of DOACs. DOACs provide important advantages in the short-term prophylaxis of VTE in patients undergoing hip or knee replacement surgery and in the longer term treatment of VTE and prevention of stroke in patients with atrial fibrillation compared with traditional agents, including reductions in dangerous bleeding types

Outcome of Patients with Venous Thromboembolism and Factor V Leiden or Prothrombin 20210 Carrier Mutations During the Course of Anticoagulation.

Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored. We used the Registro Informatizado de Enfermedad TromboEmbólica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers. Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carriers had a similar rate of venous thromboembolism recurrence (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.82-1.64), half the rate of major bleeding (adjusted HR, 0.50; 95% CI, 0.25-0.99) and a nonsignificantly lower rate of nonmajor bleeding (adjusted HR, 0.66; 95% CI, 0.43-1.01) than noncarriers. Prothrombin mutation carriers and noncarriers had a comparable rate of venous thromboembolism recurrence (adjusted HR, 1.00; 95% CI, 0.68-1.48), major bleeding (adjusted HR, 0.75; 95% CI, 0.42-1.34), and nonmajor bleeding events (adjusted HR, 1.10; 95% CI, 0.77-1.57). During the anticoagulation course, factor V Leiden carriers had a similar risk for venous thromboembolism recurrence and half the risk for major bleeding compared with noncarriers. This finding may contribute to decision-making regarding anticoagulation duration in selected factor V Leiden carriers with venous thromboembolism

Development of a Risk Prediction Score for Occult Cancer in Patients With VTE.

The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE. We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period. Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups. This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel-Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43-0.91;I-2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83-2.08;I-2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.Thrombosis and Hemostasi

Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: Findings from the RIETE Registry

Introduction The aim of this study was to investigate the recurrence rate of venous thromboembolism (VTE) and the prevalence of major bleeding or death in patients with previous VTE in pregnancy and puerperium. Risk factors for VTE recurrence were also assessed. Materials and methods We evaluated a cohort of patients enrolled in the international, multicenter, prospective Registro Informatizado de la Enfermedad Trombo-Embólica (RIETE) registry with objectively confirmed VTE. Results In the registry, 607 women were presenting with VTE that occurred during pregnancy or puerperium. The 2-year VTE recurrence rate was 3.3% (CI: 95 1.5-5.0%) and the recurrent VTE incidence rate was 2.28 events/100 patients-year. Among the 16 cases of VTE recurrence 11 cases appeared during drug treatment while only five cases were diagnosed after therapy discontinuation. No significant difference was found in treatment duration among these two subgroups of VTE recurrence cases and women without recurrence. Furthermore, the use of thrombolytics and inferior vena cava filter in initial treatment was associated to an increased risk of VTE recurrence. Conclusions The current study provides new insights on VTE recurrence rate in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) that occurred in pregnancy or postpartum period. These findings can contribute to risk assessment of thrombotic burden, thereby allowing for better decision making regarding antithrombotic management in this clinical setting

Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism

BACKGROUND: The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. RESULTS: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS: One in every three cancer patients dying of PE had recent immobilization for ≥ 4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis