Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

Abstract

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drugdrug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74-0.94] for stroke/SE; HR 0.77, 95%CI [0.65-0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86-1.01] for major bleeding; HR 0.58, 95%CI [0.50-0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99-1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients.

Efficacy of Early (≤ 24 Hours), Late (25–72 Hours), and Delayed (>72 Hours) Surgery with Magnetic Resonance Imaging-Confirmed Decompression in American Spinal Injury Association Impairment Scale Grades C and D Acute Traumatic Central Cord Syndrome Caused by Spinal Stenosis

“…Consideration of the modified Frailty index, 93-95 comorbidities, 96 and current medications including anticoagulants is important for reducing morbidity and hospital length of stay. 97,98 Multiple levels of ACDF or corpectomies in older individuals can be complicated by dysphagia and swallowing difficulty. [99][100][101][102][103] The most important imaging biological marker of tCSCI is the intramedullary lesion -the product of kinetic energy and molecular cascades immediately following trauma.…”

“…Consideration of the modified Frailty Index, 89–92 comorbidities, 92 and current medications including anticoagulants is important for reducing morbidity and hospital length of stay. 93 , 94 Multiple levels of ACDF or corpectomies in older individuals can be complicated by dysphagia and swallowing difficulty. 95–99 …”

Safety of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials

“…To explore this heterogeneity, we performed post-hoc subgroup analyses. We decided to stratify the analyses according to agent because previous systematic reviews and large real-world studies had suggested that dabigatran and rivaroxaban tend to have a higher bleeding risk than apixaban and edoxaban [13,15,16,18,20,54].…”

The Management of Anticoagulants in Patients With Atrial Fibrillation and History of Falls or Risk of Falls: The Liverpool Af-falls Project. Protocol for a Systematic Review and Meta-analysis

“…Alongside these two classes, antiplatelet agents are also prescribed despite not being recommended for stroke prevention in AF patients, regardless of stroke risks (11). In a recent meta-analysis in older AF patients, NOACs were associated with superior e cacy in preventing stroke/systemic embolism (HR 0.83, 95% CI: 0.74-0.94) and non-inferiority safety for major bleeding (HR 0.93, 95% CI: 0.86-1.01), intracranial bleeding (HR 0.58, 95% CI: 0.50-0.67) and gastrointestinal bleeding (HR 1.17, 95% CI: 0.99-1.38) compared to VKAs (12). Due to the perceived risks of bleeding, many patients are not offered anticoagulants, particularly patients at risk of falls or with history of falls.…”