Why prefer Vitamin K Antagonists (VKA) to Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) in atrial fibrillation?

From the Guidelines

Vitamin K antagonists (VKAs) may be preferred over non-vitamin K oral anticoagulants (NOACs) in certain atrial fibrillation patients, such as those with mechanical heart valves or moderate-to-severe mitral stenosis, due to their established efficacy and safety profile in these populations. According to the 2024 ESC guidelines for the management of atrial fibrillation 1, VKAs are recommended for patients with mechanical heart valves or moderate-to-severe mitral stenosis, as they are the only treatment option for these patients. Additionally, VKAs may be preferred for patients who are clinically stable with good time in therapeutic range (TTR) and have no bleeding complications, as they can be effective for thromboembolic protection with an acceptable safety profile 1.

Key Considerations

• VKAs have a higher rate of intracranial bleeding compared to NOACs, but they can be effective for thromboembolic protection with an acceptable safety profile if TTR is maintained above 70% 1.
• The use of VKAs requires frequent monitoring and dose adjustment according to the prothrombin time expressed as the international normalized ratio (INR) 1.
• Switching from VKAs to a NOAC is justified where there are concerns about intracranial bleeding or for patient-choice reasons, and a switch is recommended where patients have failed to maintain an adequate TTR (<70%) 1.
• For patients aged ≥75 years on clinically stable therapeutic VKA with polypharmacy, maintaining VKA treatment rather than switching to a DOAC may be considered to prevent excess bleeding risk 1.

Patient-Specific Factors

• Patients with mechanical heart valves or moderate-to-severe mitral stenosis should be treated with VKAs, as NOACs are contraindicated in these populations 1.
• Patients with poor medication adherence may benefit from VKAs, as INR monitoring provides a way to verify compliance 1.
• Patients who are already well-controlled on warfarin (time in therapeutic range >70%) with stable INRs and no bleeding complications may continue VKA therapy rather than switching to a NOAC 1.

From the FDA Drug Label

The trials in non-valvular atrial fibrillation support the American College of Chest Physicians’ (7th ACCP) recommendation that an INR of 2.0-3.0 be used for warfarin therapy in appropriate AF patients. There is no direct information in the provided drug labels that supports preferring VKA to NOAC in atrial fibrillation. Key points:

• The labels provide information on the use of warfarin and rivaroxaban in non-valvular atrial fibrillation, but do not directly compare the two or provide a preference for one over the other.
• The ROCKET AF study compared rivaroxaban to warfarin, but the results showed that rivaroxaban was non-inferior to warfarin, not superior 2. Therefore, no conclusion can be drawn about preferring VKA to NOAC in atrial fibrillation based on the provided drug labels.

From the Research

Preference for VKA over NOAC in Atrial Fibrillation

There are specific scenarios where Vitamin K antagonists (VKAs) might be preferred over non-vitamin K antagonist oral anticoagulants (NOACs) in the management of atrial fibrillation. The decision to use VKAs or NOACs depends on various factors, including patient characteristics, comorbidities, and the presence of specific conditions.

Patient Characteristics and Conditions

• Patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis may require VKAs due to the lack of evidence supporting the use of NOACs in these populations 3.
• Individuals with significant drug-drug interactions or those who cannot afford NOACs due to their higher costs may also be candidates for VKA therapy 3.
• Patients with advanced chronic kidney disease (CKD) or those on dialysis may benefit from NOACs, which have been shown to have a favorable safety profile compared to VKAs in these populations 4, 5, 6.
• The choice between VKAs and NOACs should also consider patient preference, as well as the potential for food and drug interactions, and concerns about bleeding complications 7.

Clinical Evidence

• A study published in 2023 found that NOACs are preferable over VKAs in the large majority of eligible patients with atrial fibrillation and thromboembolic risk factors, except in cases with mechanical heart valves or moderate/severe rheumatic mitral stenosis 3.
• Another study from 2020 demonstrated that apixaban caused less major bleeding compared to warfarin in patients with atrial fibrillation and advanced CKD 4.
• A nationwide cohort study from 2019 showed that NOACs were associated with a lower risk of major bleeding compared to VKAs in patients with atrial fibrillation and CKD not receiving dialysis 5.
• A meta-analysis from 2021 found that rivaroxaban or apixaban were safe and at least as effective as warfarin in patients with atrial fibrillation and stage 4-5 CKD or on dialysis 6.