Questions Remain Regarding Venous Thromboembolism Recurrence in Older Adults

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Venous thromboembolism recurrence risk may not be any higher in older patients than in younger patients.
Venous thromboembolism recurrence risk may not be any higher in older patients than in younger patients.

Venous thromboembolism (VTE), including deep vein thrombosis involving the lower limbs and pulmonary embolism, is the third most commonly reported cardiovascular event, after acute coronary disease and stroke. But while research has shown that the risk of developing VTE increases with age, research regarding the effect of aging on the risk of recurrence is limited. In a review paper published in Expert Review of Hematology, Gualtiero Palareti, MD, of the University of Bologna in Italy, and Daniela Poli, MD, of Azienda Ospedaliero-Universitaria Careggi in Italy, discussed the recent literature on VTE recurrence and bleeding risks in elderly patients being treated with older anticoagulants and newer direct oral anticoagulants (DOACs).

VTE incidence rises from approximately 1 per 10,000 in individuals between the ages of 25 to 30 years to almost 80 per 10,000 in individuals aged 85 years or older. Additionally, VTE is considered a chronic disease because of the high risk of recurrence. Some data show that the cumulative incidence of recurrence at 10 years after cessation of anticoagulant therapy can reach 50% in patients with idiopathic events and approximately 20% in those with secondary events. However, the authors noted, although studies have shown mixed results, the risk of recurrent VTE events in elderly patients may not be any higher, and may even be lower, than in younger patients. Overall, the true risk of recurrence in elderly patients remains unclear, but considering both the high rate of VTE events in elderly patients and the growing population of older adults, “the issue of recurrent VTE and its prevention in this patient setting has a great clinical and social relevance.”

All elderly patients with acute VTE, in the absence of any absolute contraindication to anticoagulation therapy, should be treated as soon as the diagnosis has been made, suggested the authors. Therapy with vitamin K antagonists (VKAs) or DOACs should be given for at least 3 months to patients who have experienced idiopathic or secondary events. Some experts recommend 3 to 6 months of therapy. However, the authors noted that while shorter courses of therapy have been associated with a higher risk of recurrence, longer durations have had no effect on recurrence due to protection against VTE ending when anticoagulation is stopped.

Anticoagulation therapy carries a risk of bleeding. The authors pointed to a 2006 study that compared the clinical characteristics and 3-month outcomes of patients with VTE who were 80 years or older with those of a younger cohort. The rate of bleeding for the younger cohort was 2.1% compared with 3.4% for patients 80 years and older (odds ratio 1.7). Another study looking at bleeding rates of patients under 65 years old compared with patients older than 65 found those rates to be 4.8% and 9.2 % (P <.001), respectively, at 30 days after an acute episode, and 6.6% and 13.2%, respectively, after 1 year (P <.001).

“If this high recurrence incidence justifies indefinite anticoagulant treatment after [an] idiopathic event, it should be the result of a balanced evaluation between the recurrence and bleeding risk,” the authors wrote. “It should especially be borne in mind that the entire [patient] population will be exposed to bleeding risk, whereas only a part (half at maximum) would be at risk of recurrence.”

However, most of the current data assessing the balance between risk of recurrence and risk of bleeding comes from studies that used VKAs, despite the increasing usage of DOACs for initial, long-term, and extended VTE treatment. The specific benefit/risk balance needs to be addressed for these agents. Although recent trials on DOAC usage for extended treatment have yielded positive results, the trials were conducted on the general VTE population, with a lower proportion of elderly patients participating and with elderly patients experiencing short durations of treatment.

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