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
