Long-term predictors and causes of death are understudied in elderly patients with acute venous thromboembolism.
Methods
We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was overall mortality. We explored the association between patient baseline characteristics and mortality, adjusting for other baseline variables and periods of anticoagulation as a time-varying covariate. Causes of death over time were adjudicated by a blinded, independent committee.
Results
The median age was 75 years. During a median follow-up period of 30 months, 206 patients (21%) died. Independent predictors of overall mortality were age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.05-1.65, per decade), active cancer (HR, 5.80; 95% CI, 4.22-7.97), systolic blood pressure <100 mm Hg (HR, 2.77; 95% CI, 1.56-4.92), diabetes mellitus (HR, 1.50; 95% CI, 1.02-2.22), low physical activity level (HR, 1.92; 95% CI, 1.38-2.66), polypharmacy (HR, 1.41; 95% CI, 1.01-1.96), anemia (HR, 1.48; 95% CI, 1.07-2.05), high-sensitivity C-reactive protein >40 mg/L (HR, 1.88; 95% CI, 1.36-2.60), ultra-sensitive troponin >14 pg/mL (HR, 1.54; 95% CI, 1.06-2.25), and D-dimer >3000 ng/mL (HR, 1.45; 95% CI, 1.04-2.01). Cancer (34%), pulmonary embolism (18%), infection (17%), and bleeding (6%) were the most common causes of death.
Conclusions
Elderly patients with acute venous thromboembolism have a substantial long-term mortality, and several factors, including polypharmacy and a low physical activity level, are associated with long-term mortality. Cancer, pulmonary embolism, infections, and bleeding are the most common causes of death in the elderly with venous thromboembolism.
The incidence of venous thromboembolism increases sharply with age, with 27 cases per 100,000 person-years in persons aged ≤40 years to 410 cases in those aged ≥65 years.1 Patients aged 65 years or more comprise more than 60% of venous thromboembolism cases occurring in the community setting.2 The elderly not only have a higher incidence of venous thromboembolism but also have an approximately 2-fold increase in major bleeding and 2- to 3-fold greater risk of all-cause mortality over time than younger patients.2 Despite the higher morbidity and mortality, venous thromboembolism remains understudied in the elderly,2 and little is known about the predictors and causes of death in older patients with venous thromboembolism. Prior studies reporting predictors and causes of death in elderly patients with venous thromboembolism were limited by a retrospective design,2, 3, 4identified cases with venous thromboembolism using diagnosis codes rather than predefined clinical criteria,2failed to report causes of death,2, 5, 6 or determined the cause of death without the use of a formal adjudication process.4, 7, 8, 9 Moreover, these studies almost exclusively focused on short-term mortality (<6 months),3, 4, 5, 7, 8,9 and predictors and causes of long-term mortality remain largely unknown in the elderly with venous thromboembolism. To fill these gaps of knowledge, we aimed to examine which factors drive long-term mortality and to determine causes of death in a multicenter prospective study of elderly patients with acute venous thromboembolism using a formal mortality adjudication process.
Materials and Methods
Cohort Sample
This study was conducted between September 2009 and December 2013 as part of a prospective multicenter cohort study that assessed long-term medical outcomes and quality of life in elderly patients with acute symptomatic venous thromboembolism from all 5 university and 4 high-volume nonuniversity hospitals in Switzerland (SWITCO65+).10
Consecutive patients aged ≥65 years with an acute, objectively confirmed venous thromboembolism were identified in the inpatient and outpatient services of all participating study sites. We defined symptomatic deep vein thrombosis as an acute onset of leg pain or swelling plus incomplete compressibility of a venous segment on ultrasonography or an intraluminal filling defect on contrast venography.11 For iliac and caval deep vein thrombosis, abnormal duplex flow patterns compatible with thrombosis or an intraluminal filling defect on computed tomography or magnetic resonance imaging venography were used as additional diagnostic criteria.12,13, 14 Patients with isolated distal vein thrombosis were eligible only if the incompressible distal vein diameter was at least 5 mm.15, 16 We defined symptomatic pulmonary embolism as a positive computed tomography or pulmonary angiography, a high-probability ventilation-perfusion scan, or a proximal deep vein thrombosis confirmed by compression ultrasonography or contrast venography in patients with acute chest pain, new or worsening dyspnea, hemoptysis, or syncope.17, 18
Exclusion criteria included inability to provide informed consent (ie, severe dementia), impossible follow-up (ie, because of terminal illness), insufficient German or French speaking ability, thrombosis at a different site than lower limb, catheter-related thrombosis, or prior enrollment in the cohort. Ethics committees at each hospital approved the study, and all patients underwent written informed consent.
Baseline Data Collection
Study nurses collected baseline demographics (age, gender), body mass index, lifestyle factors (smoking status, physical activity level), comorbidities (diabetes mellitus, arterial hypertension, active cancer, cardiac disease, cerebrovascular disease, chronic lung disease, chronic liver disease, chronic renal disease, recent major bleeding, recent major surgery, immobilization >3 days during the last 3 months, and risk of falls), vital signs (altered mental status, heart rate, temperature, respiratory rate, systolic blood pressure, and arterial oxygen saturation), laboratory findings (hemoglobin, creatinine, platelet count, ultra-sensitive troponin, N-terminal pro B-type natriuretic peptide, high-sensitivity C-reactive protein, high-sensitivity D-dimer), and treatments at the time of diagnosis (concomitant antiplatelet therapy, polypharmacy, anticoagulation before index venous thromboembolism, vitamin K antagonist therapy, and type of initial parenteral anticoagulation) using standardized data collection forms. The risk of falls was assessed using 2 validated screening questions: 1) Did you fall during the last year? 2) Did you notice any problem with gait, balance, or mobility?19 Patients who answered yes to at least 1 screening question were considered to be at high risk of falls. Polypharmacy was defined as the prescription of more than 4 drugs, including St John’s wort, at the time of the index venous thromboembolism event.20
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-Nicolas Faller, MD, PhD, Andreas Limacher, PhD, MAS, MSc, Marie Méan, MD, Marc Righini, MD, Markus Aschwanden, MD, Jürg Hans Beer, MD, Beat Frauchiger, MD, Josef Osterwalder, MD, MPH, Nils Kucher, MD, Bernhard Lämmle, MD, Jacques Cornuz, MD, MPH, Anne Angelillo-Scherrer, MD, Christian M. Matter, MD, Marc Husmann, MD, Martin Banyai, MD, Daniel Staub, MD, Lucia Mazzolai, MD, PhD, Olivier Hugli, MD, Nicolas Rodondi, MD, MAS, Drahomir Aujesky, MD, MSc
This article originally appeared in the February 2017 issue of The American Journal of Medicine.
