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Semin Thromb Hemost 2018; 44(04): 377-387
DOI: 10.1055/s-0038-1642644
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Causes of Death in Patients with Venous Thromboembolism Anticoagulated with Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis

Antonio Gómez-Outes
1   Division of Pharmacology and Clinical Drug Evaluation, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain
,
Ana Isabel Terleira-Fernández
2   Department of Clinical Pharmacology, Hospital Clínico San Carlos, Madrid, Spain
3   Department of Pharmacology, Universidad Complutense, Madrid, Spain
,
Ramón Lecumberri
4   Hematology Service, University Clinic of Navarra, Pamplona, Spain
5   Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
,
Mª Luisa Suárez-Gea
1   Division of Pharmacology and Clinical Drug Evaluation, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain
,
Gonzalo Calvo-Rojas
6   Department of Clinical Pharmacology, Hospital Clinic, Barcelona, Spain
,
Emilio Vargas-Castrillón
2   Department of Clinical Pharmacology, Hospital Clínico San Carlos, Madrid, Spain
3   Department of Pharmacology, Universidad Complutense, Madrid, Spain
› Author Affiliations Funding No funding/grant support was received for conducting this systematic review.
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Publication History

Publication Date:
03 May 2018 (online)

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Abstract

Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3–4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2–25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed.

Keywords

venous thromboembolism - anticoagulation - mortality - death - cancer

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