Oral anticoagulant therapy in older adults

Patients aged >65 years not only account for the majority of patients with atrial fibrillation (AF) and venous thromboembolism (VTE), they are also at a higher risk of morbidity, mortality, and undertreatment than younger patients. Several age-related physiological changes with effects on drug pharmacokinetics/-dynamics and blood vessel fragility as well as the higher prevalence of geriatric conditions such as frailty, multimorbidity, polypharmacy, fall risk, dementia, and malnutrition make older persons more vulnerable to disease- and anticoagulation-related complications. Moreover, because older patients with AF/VTE are underrepresented in oral anticoagulation (OAC) trials, evidence on OAC in older adults with AF/VTE is mainly based on subgroup analyses from clinical trials and observational studies. A growing body of such limited evidence suggests that direct oral anticoagulants (DOACs) may be superior in terms of efficacy and safety compared to vitamin K antagonists in older persons with AF/VTE and that specific DOACs may have a differing risk-benefit profile. In this narrative review, we summarize the evidence on epidemiology of AF/VTE, impact of age-related physiological changes, efficacy/safety of OAC, specifically considering individuals with common geriatric conditions, and review OAC guideline recommendations for older adults with AF/VTE. We also propose a research agenda to improve the evidence basis on OAC older individuals with AF/VTE, including the conduct of advanced agespecific and pragmatic studies using less restrictive eligibility criteria and patient-reported health outcomes, in order to compare the effectiveness and safety of different DOACs, and investigate lower-dose regimens and optimal OAC durations in older patients.