Unmet Clinical Needs in Elderly Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation

Abstract

Vitamin K antagonists have been used for many years as the treatment of choice for long-term oral anticoagulation in patients with non-valvular atrial fibrillation. Unfortunately, the use of those drugs in the real-world setting, particularly among elderly patients, is suboptimal because of their limitations in management. Therefore, many patients were not adequately anticoagulated. Direct oral anticoagulants have been demonstrated to overcome almost all the limitations derived from the use of vitamin K antagonists. Direct oral anticoagulants are at least as effective as vitamin K antagonists in preventing thromboembolic events in patients with non-valvular atrial fibrillation and safer in reducing the risk of intracranial haemorrhage and all-cause mortality. However, as a result of the strict inclusion and exclusion criteria applied to patients, data coming from randomized controlled trials might not apply to the general population. Furthermore, elderly patients were scarcely represented in randomized controlled trials with direct oral anticoagulants. Therefore in elderly patients with non-valvular atrial fibrillation, unmet clinical needs still exist. This review article highlights some of them and provides potential answers based on the results coming from randomized clinical trials, real-world data, and the authors’ clinical experience.

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

“…These results are clinically important because limited randomized data exist for such patients, as patients with recent stroke within 7 days, 35 14 days, 36,37 or 30 days, 7 respectively, were excluded from the pivotal DOAC RCTs and the oldest old were severely underrepresented, constituting less than 5% of the RCTs population 8,9 . While several large observational studies later confirmed the benefits of DOAC in elderly patients with AF, 38–43 they did not examine patients with a recent ischemic stroke.…”

“…The median age was 78 years (IQR 71-84, range 24-102); 1,380 (23.1%) patients were aged ≥85 years and 4,604 (76.9%) were aged <85 years. OAC was initiated at a median (IQR) of 5 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) days after the index event with DOAC in 3,688 patients (61.6%) and VKA in 2,296 patients (38.4%).…”

“…In the current guidelines, 3 direct oral anticoagulants (DOAC) are recommended in patients with AF for recurrent stroke prevention in preference to vitamin K antagonists (VKA) based on the results of the pivotal DOAC randomized controlled trials (RCTs) 4 . However, it is less clear whether this preference can be generalized to include patients: (1) aged ≥85 years, who made up less than 5% of the RCTs population 5–7 ; or, (2) with recent ischemic stroke, who had been excluded from the RCTs for at least some weeks after stroke 8,9 …”

“… 4 However, it is less clear whether this preference can be generalized to include patients: (1) aged ≥85 years, who made up less than 5% of the RCTs population 5 , 6 , 7 ; or, (2) with recent ischemic stroke, who had been excluded from the RCTs for at least some weeks after stroke. 8 , 9 …”

Many Good Reasons to Switch from Vitamin K Antagonists to Non-Vitamin K Antagonists in Patients with Non-Valvular Atrial Fibrillation

“…However, it needs to be considered that there are no outcome data for NOACs in patients with advanced CKD (creatinine clearance <30 mL/min), and there are conflicting data regarding the benefits and risks of these medications in end-stage renal disease (creatinine clearance <15 mL/min) [85]. At present, the alternatives to VKA in those CKD stages are limited to left atrial appendage occlusion, antiplatelet therapy, or even no anticoagulation [86].…”