Direct Oral Anticoagulants or Standard Anticoagulant Therapy in Fragile Patients with Venous Thromboembolism

Juan J. López-Núñez; Ricard Pérez-Andrés; Pierpaolo Di Micco; Sebastian Schellong; Covadonga Gómez-Cuervo; Joan Carles Sahuquillo; Maurizio Ciammaichella; Maria del Valle Morales; Marijan Bosevski; Manuel Monreal; and the RIETE Investigators

doi:10.1055/s-0039-1683970

TH Open, Inhaltsverzeichnis

CC BY 4.0 · TH Open 2019; 03(01): e67-e76
DOI: 10.1055/s-0039-1683970

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Direct Oral Anticoagulants or Standard Anticoagulant Therapy in Fragile Patients with Venous Thromboembolism

Authors

Juan J. López-Núñez

¹Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
Ricard Pérez-Andrés

²Department of Radiology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
Pierpaolo Di Micco

³Department of Internal Medicine and Emergency Room, Ospedale Buon Consiglio Fatebenefratelli, Naples, Italy
Sebastian Schellong

⁴Department of Medical Clinic, Municipal Hospital of Dresden Friedrichstadt, Dresden, Germany
Covadonga Gómez-Cuervo

⁵Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
Joan Carles Sahuquillo

⁶Department of Internal Medicine, Hospital Municipal de Badalona, Barcelona, Spain
Maurizio Ciammaichella

⁷Department of Emergency Internal Medicine, Ospedale St. John, Rome, Italy
Maria del Valle Morales

⁸Department of Internal Medicine, Hospital del Tajo, Madrid, Spain
Marijan Bosevski

⁹University Cardiology Clinic, Faculty of Medicine, Skopje, Republic of Macedonia
Manuel Monreal

¹Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain

and the RIETE Investigators

Abstract

Background The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance levels ≤ 50 mL/min and/or body weight ≤ 50kg) with venous thromboembolism (VTE) has not been evaluated.

Methods We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of DOACs or standard anticoagulant therapy.

Results From January 2013 to April 2018, 24,701 patients were recruited. Of these, 10,054 (41%) were fragile. Initially, 473 fragile patients (4.7%) received DOACs and 8,577 (85%) low-molecular-weight heparin (LMWH). For long-term therapy, 1,298 patients (13%) received DOACs and 5,038 (50%) vitamin K antagonists (VKAs). Overall, 95 patients developed VTE recurrences and 262 had major bleeding. Patients initially receiving DOACs had a lower rate of the composite outcome (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.08–0.88) than those on LMWH. Patients receiving DOACs for long-term therapy had a nonsignificantly lower rate of the composite outcome (HR: 0.70; 95% CI: 0.46–1.03) than those on VKAs. On multivariable analysis, patients initially receiving DOACs had a nonsignificantly lower risk for the composite outcome (HR: 0.36; 95% CI: 0.11–1.15) than those on LMWH, while those receiving DOACs for long-term therapy had a significantly lower risk (HR: 0.61; 95% CI: 0.41–0.92) than those on VKAs.

Conclusions Our data suggest that the use of DOACs may be more effective and safe than standard therapy in fragile patients with VTE, a subgroup of patients where the risk for bleeding is particularly high.

Keywords

venous thromboembolism - fragile patients - direct oral anticoagulants

Volltext

Referenzen

References
1 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
2 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
3 Moustafa F, Pierfranceschi MG, Di Micco P. , et al. Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism. Res Pract Thromb Haemost 2017; 1 (02) 172-179
4 Ruíz-Giménez N, Suárez C, González R. , et al; RIETE Investigators. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100 (01) 26-31
5 Muñoz-Torrero JF, Bounameaux H, Pedrajas JM. , et al; Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Investigators. Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis. J Vasc Surg 2011; 54 (06) , Suppl): 26S-32S
6 Jiménez D, de Miguel-Díez J, Guijarro R. , et al; RIETE Investigators. Trends in the management and outcomes of acute pulmonary embolism: Analysis from the RIETE Registry. J Am Coll Cardiol 2016; 67 (02) 162-170
7 Muriel A, Jiménez D, Aujesky D. , et al; RIETE Investigators. Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk. J Am Coll Cardiol 2014; 63 (16) 1675-1683
8 Bikdeli B, Jimenez D, Hawkins M. , et al; RIETE Investigators. Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 2018; 118 (01) 214-224
9 Bauersachs R, Agnelli G, Gitt AK. , et al; PREFER in VTE Scientific Steering Committee. The role of heparin lead-in in the real-world management of acute venous thromboembolism: the PREFER in VTE registry. Thromb Res 2017; 157: 181-188
10 Cohen AT, Gitt AK, Bauersachs R. , et al. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry. Thromb Haemost 2017; 117 (07) 1326-1337
11 Schulman S, Kearon C, Kakkar AK. , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
12 Büller HR, Prins MH, Lensin AW. , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
13 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
14 Becattini C, Agnelli G. Treatment of venous thromboembolism with new anticoagulant agents. J Am Coll Cardiol 2016; 67 (16) 1941-1955
15 Coleman CI, Turpie AGG, Bunz TJ, Beyer-Westendorf J. Effectiveness and safety of rivaroxaban versus warfarin in frail patients with venous thromboembolism. Am J Med 2018; 131 (08) 933.e1-938.e1
16 Buchner DM, Wagner EH. Preventing frail health. Clin Geriatr Med 1992; 8 (01) 1-17
17 Rockwood K, Song X, MacKnight C. , et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005; 173 (05) 489-495
18 Robinson TN, Eiseman B, Wallace JI. , et al. Redefining geriatric preoperative assessment using frailty, disability and co-morbidity. Ann Surg 2009; 250 (03) 449-455
19 Robinson TN, Wu DS, Pointer L, Dunn CL, Cleveland Jr JC, Moss M. Simple frailty score predicts postoperative complications across surgical specialties. Am J Surg 2013; 206 (04) 544-550
20 Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009; 38 (02) 156-162
21 Trujillo-Santos J, Di Micco P, Dentali F. , et al; RIETE Investigators. Real-life treatment of venous thromboembolism with direct oral anticoagulants: the influence of recommended dosing and regimens. Thromb Haemost 2017; 117 (02) 382-389
22 Monreal M, Falgá C, Valle R. , et al; RIETE Investigators. Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry. Am J Med 2006; 119 (12) 1073-1079
23 Moustafa F, Stehouwer A, Kamphuisen P. , et al; RIETE Investigators. Management and outcome of major bleeding in patients receiving vitamin K antagonists for venous thromboembolism. Thromb Res 2018; 171: 74-80