Little is known about predictors and outcomes of recurrent venous thromboembolism in elderly patients.
Methods
We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was symptomatic recurrent venous thromboembolism. We explored the association between baseline characteristics and treatments and recurrent venous thromboembolism using competing risk regression, adjusting for periods of anticoagulation as a time-varying covariate. We also assessed the clinical consequences (case-fatality, localization) of recurrent venous thromboembolism.
Results
During a median follow-up period of 30 months, 122 patients developed recurrent venous thromboembolism, corresponding to a 3-year cumulative incidence of 14.8%. The case-fatality of recurrence was high (20.5%), particularly in patients with unprovoked (23%) and cancer-related venous thromboembolism (29%). After adjustment, only unprovoked venous thromboembolism (sub-hazard ratio, 1.67 compared with provoked venous thromboembolism; 95% confidence interval, 1.00-2.77) and proximal deep vein thrombosis (sub-hazard ratio, 2.41 compared with isolated distal deep vein thrombosis; 95% confidence interval, 1.07-5.38) were significantly associated with recurrence. Patients with initial pulmonary embolism were more likely to have another pulmonary embolism as a recurrent event than patients with deep vein thrombosis.
Conclusions
Elderly patients with acute venous thromboembolism have a substantial long-term risk of recurrent venous thromboembolism, and recurrence carries a high case-fatality rate. Only 2 factors, unprovoked venous thromboembolism and proximal deep vein thrombosis, were independently associated with recurrent venous thromboembolism, indicating that traditional risk factors for venous thromboembolism recurrence (eg, cancer) may be less relevant in the elderly.
Introduction
Venous thromboembolism, pulmonary embolism, and deep venous thrombosis are common and have a high impact on morbidity and mortality.1 Because venous thromboembolism tends to recur,2, 3 the risk of recurrence is an important determinant of the duration of anticoagulant therapy. Several patient characteristics are associated with recurrent venous thromboembolism, including age,3, 4 male sex,3, 5 obesity,4 localization of venous thromboembolism,6, 7 unprovoked venous thromboembolism,3, 8 cancer-related venous thromboembolism,2, 3prior venous thromboembolism,9 family history of venous thromboembolism,10 inflammatory bowel disease,11chronic heart failure,12 leg paresis,13 varicose veins,4 elevated D-dimer at baseline,14 or thrombophilia.10, 15Treatment-related factors associated with venous thromboembolism recurrence include a suboptimal anticoagulation quality and the insertion of a vena cava filter,2, 16 whereas thrombolysis,17 initial therapy with low-molecular-weight heparin,18 and concomitant use of statins or antiplatelet therapy may have a protective effect.3,19 Bleeding episodes also may be followed by a higher risk of recurrent venous thromboembolism, possibly because of the interruption of anticoagulation.20 Elevated D-dimer after stopping anticoagulation and residual vein obstruction are also associated with recurrent venous thromboembolism.21, 22
Although elderly patients have a higher risk of venous thromboembolism due to multimorbidity and prothrombotic hemostasis,23, 24 and persons aged ≥65 years comprise 55% of patients with acute venous thromboembolism,20little is known about predictors and outcomes of recurrent venous thromboembolism in older patients. Prior studies reporting predictors of recurrent venous thromboembolism in the elderly were limited by a retrospective study design,20 use of administrative rather than clinical data,20 lack of information on anticoagulation duration or quality,12, 20 or a follow-up of up to 3 months only.12 To fill this gap of knowledge, we explored the association among patient characteristics, treatments, and the long-term risk of recurrent venous thromboembolism in a prospective cohort of elderly patients with acute venous thromboembolism. We also assessed the localization and the clinical consequences of recurrent venous thromboembolism.
Methods
Cohort Sample
The 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 symptomatic venous thromboembolism from all 5 university and 4 high-volume nonuniversity hospitals in Switzerland. Consecutive patients aged ≥65 years with objectively confirmed symptomatic pulmonary embolism or deep vein thrombosis were identified in the inpatient and outpatient services of all participating study sites. Exclusion criteria were inability to provide informed consent (ie, severe dementia), conditions incompatible with follow-up (ie, terminal illness or place of living too far away from the study center), insufficient German or French-speaking ability, thrombosis at a different site than lower limb, catheter-related thrombosis, or previous enrollment in the cohort. The study was approved by the institutional review board at each participating site. A detailed description of the study methods has been published.25
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-Sandro Lauber, MD, Andreas Limacher, PhD, MAS, MSc, Tobias Tritschler, MD, Odile Stalder, 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 June issue of The American Journal of Medicine.
