Perspective:

In the pivotal phase 3 trials comparing NOAC to VKA therapy in AF, NOAC therapy was consistently associated with lower rates of bleeding, especially intracranial hemorrhage. Therefore, many clinicians assume that patients who are using VKA therapy could reduce their risk of bleeding by switching to NOAC therapy. The FRAIL-AF study suggests that among older, frail patients who were tolerating VKA therapy, switching to NOACs actually leads to higher rates of bleeding. This likely reflects two important concepts. First, NOACs target a very specific spot in the coagulation cascade, and therefore, may have different risks of bleeding in different patients. Thus, a patient who is tolerating a VKA (which indirectly inhibits factors II, VII, IX, X) may actually experience bleeding with switching to a medication that directly inhibits factor Xa. Second, older, frail patients often are using several medications that may interact with NOACs. While these medications also interact with VKA, the use of frequent INR testing can quickly adjust for these interactions. Without laboratory monitoring, these drug-drug interactions may lead to elevated blood levels of the different DOAC medications.

Clinicians should be cautious about automatically switching older, frail patients with AF from VKA therapy to NOAC therapy if the patient is tolerating VKA therapy. For any patient being started on NOAC therapy, careful assessment for potential drug-drug interactions is critical.