Oral Anticoagulant Mistakes to Avoid in Older Adults With AF

Mauricio Wajngarten, MD

December 23, 2022

The relevance of oral anticoagulants (OACs) for older adults with atrial fibrillation (AF) does not need to be reiterated.

It has been posited that the availability of direct oral anticoagulants (DOACs) would substantially increase the prevention of thromboembolic events in older adults with AF, given the superior safety profile of these agents and the relative ease of use. Nevertheless, several factors, especially the risk of hemorrhage, may influence the nonprescription or inappropriate prescription of these medications, as well as nonadherence to treatment.

Two recent studies are helpful regarding these factors.

The Studies

The first is a retrospective cohort study conducted using administrative claims data from Optum’s Clinformatics Data Mart. Participants included 381,488 beneficiaries of Medicare Advantage plans who were aged 65 years or older and who had AF and were at elevated risk of ischemic stroke. The study assessed trends in OAC initiation and DOAC uptake from 2010 to 2020 among older adults with new AF who were at elevated risk of stroke. It also evaluated patient characteristics associated with noninitiation of OAC and DOAC after new AF diagnosis and trends in OAC nonadherence.

In comparing data from 2010 with those from 2020, the main results were as follows:

1. The rate of OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26,782 patients) in 2010 to 32.9% (7111 of 21,603 patients) in 2020.
2. The rate of DOAC uptake increased from 1.1% (291 of 26,782 patients) to 30.9% (6678 of 21,603 patients).
3. Older age (odds ratio [OR], 0.98; 95% CI, 0.98 – 0.98), dementia (OR, 0.57; 95% CI, 0.55 – 0.58), frailty (OR, 0.74; 95% CI, 0.72 – 0.76), and anemia (OR, 0.75; 95% CI, 0.74 – 0.77) were associated with lower odds of OAC initiation.
4. The rate of OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients).

The second article is a meta-analysis of 106 observational studies published in English between 2008 and 2020. It examined outcomes of, or factors associated with, inappropriate dosing (underdosing and overdosing) of a DOAC in adults with AF.

Compared with recommended DOAC dosing, the main outcomes were as follows:

1. Overdosing was associated with an increased risk of major bleeding, as expected.
2. Off-label underdosing was associated with a null effect on stroke outcomes (ischemic stroke and stroke/transient ischemic attack [TIA], stroke/systemic embolism [SE] and stroke/SE/TIA). It was also associated with a null effect of underdosing on bleeding outcomes (perhaps unexpected) but an increased risk of all-cause mortality.
3. The factors associated with underdosing were increased age, history of minor bleeding, hypertension, congestive heart failure, and low creatinine clearance.

Implications

The most common known reasons for not using warfarin are risk of bleeding, risk of falling, frailty, cognitive impairment, and challenges of adherence. In addition, pharmacologic, clinical, and preferential aspects must be carefully considered. Education, monitoring, and decision-sharing are essential.

Two studies highlight the following challenges:

1. In the past decade, the availability of DOACs improved uptake of OACs in older adults with AF, particularly those at high risk of bleeding events. Nevertheless, generalized OAC use among older adults remains lower than 50%, especially in patients with dementia, frailty, and anemia. In fact, severe bleeding risk is two times higher among patients with six or more comorbidities than among patients with up to two comorbidities.
2. Off-label DOAC underdosing does not reduce the occurrence of bleeding and is associated with an increased risk of call-cause mortality. These data emphasize the importance of adherence to the dosing guidelines of these medications and of refraining from “intuitive underdosing” to avoid bleeding.

It is important to highlight the following points:

1. Falls are not an absolute contraindication for the prescription of anticoagulants, since patients at risk of falling are excluded from studies, and data suggest that the benefits of OACs exceed the risk of bleeding in patients with a CHA₂DS₂-VASc score >3 with regard to falls.
2. One study suggests that DOACs are associated with lower risk of intracranial bleeds in older adults who have a fall.
3. Recent data emphasize the benefits of OACs, particularly DOACs, for frail patients with AF.

There is need for improvement regarding the efficient and safe treatment of older patients with AF, particularly those considered at risk with respect to OAC use. One path to this may be a multidisciplinary approach involving patients, caregivers, primary care physicians, geriatricians, general cardiologists, electrophysiologists, pharmacists, and other associated persons.

A reassuring perspective is the development of a new class of anticoagulants, the factor Xia inhibitors, which are in phase 2 studies and may reduce risk of bleeding in comparison with factor Xa inhibitors.

For now, all that can be done is to follow the guidance recommendations and offer personalized treatment with caution but without missing out on anything.