Non-vitamin K antagonist oral anticoagulants in older and frail patients with atrial fibrillation

Abstract

Elderly and frail patients with atrial fibrillation (AF) are at increased risk of thrombotic events, bleeding, and death compared to their counterparts, making their management challenging. With the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in the past decade, the risk:benefit balance in such high-risk patients with AF has tipped in favor of treating these patients with anticoagulation, and in most cases with a NOAC instead of a VKA. In patients ≥75 years of age with AF, each of the 4 approved NOACs reduced stroke or systemic embolism and vs warfarin in their landmark clinical trial and lowered mortality. However, only apixaban and edoxaban significantly reduced major bleeding vs warfarin. A similar pattern was seen in even older cohorts (≥80 and ≥85 years). Among patients age ≥80 who are not candidates for oral anticoagulants at the approved dose, edoxaban 15 mg may be a reasonable alternative. In elderly or frail individuals who are on multiple comedications (particularly if ≥1 moderate or strong cytochrome P-450 inhibitor), only edoxaban consistently reduced major bleeding compared to warfarin. Regardless of the specific OAC selected, appropriate dosing in the elderly (who frequently qualify for dose reduction per the prescribing label) is critical. In elderly and frail patients with AF, factors that may modify the efficacy-safety profile of specific oral OACs should be carefully considered to permit the optimal selection and dosing in these vulnerable patients.

Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: a Narrative Review

“…In summary, DOACs have been found to be safer and more effective than warfarin for the treatment of NVAF in older and frail patients. Apixaban and edoxaban seem to provide the best combination of efficacy and safety in these patient populations [ 3 , 57 , 66 ].…”

“…In some patients (e.g., severe CKD, mechanical heart valves, valvular AF or major drug interactions, extreme body weights), only VKAs are indicated. In DOAC-eligible patients, based on the above reported literature evidence and expert opinions, it can be suggested to match the optimal DOAC to the patient profile, especially in those with AF, with the aim of reducing the risk of complications [ 66 , 85 , 148 – 150 ] (Fig. 2 ).…”

“…In the elderly (≥ 75 years old) or frail NVAF patients, apixaban followed by edoxaban may be the first choice due to the excellent efficacy–safety profile demonstrated in these subpopulations, while dabigatran and rivaroxaban may be considered secondarily in those at low-bleeding risk [ 57 , 63 , 66 ]. All FXa inhibitors are viable options in elderly patients with VTE, while dabigatran 150 mg should not be the first choice, given the increased risk of MB reported in this subgroup in pooled data of RECOVER I and II [ 151 ].…”

Antithrombotic treatment switching in elderly patients with atrial fibrillation and the risk of thromboembolism, bleeding, and cardiac death

“…In subgroup analyses from the ARISTOTLE and ENGAGE AF‐TIMI 48 trials of patients aged 80 years or older, an equivalent risk of thromboembolism was observed between DOACs and warfarin, yet a decreased risk of major bleeding for DOAC was reported. 21 Also, a patient‐level meta‐analysis of the COMBINE AF database ( n = 71,683), including all patients from the four pivotal trials comparing DOACs to warfarin, showed better efficacy and safety for DOACs compared to warfarin across all ages. 3 Principally, our finding highlights the importance of a broad inclusion strategy of elderly patients in all studies, irrespective of comorbidity status and organ function.…”

Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis

“…Balancing the benefits and risks of anticoagulation in such patients is a significant challenge for clinicians. Available studies confirmed that most frail patients, whether formally assessed or not, should receive OAC because the benefit outweighs the absolute risk of bleeding (25). However, guidelines do not give clear recommendations on the dosage and specific types of OAC to prescribe, and there is a paucity of relevant studies on frail patients.…”