Direct oral anticoagulants for atrial fibrillation On comparing apples and oranges

Atrial fibrillation is the most common sustained cardiac arrhythmia. It increases the risk of thromboembolism, which oral anticoagulants reduce effectively. For decades, vitamin K antagonists were the only class of oral anticoagulants available, but their narrow therapeutic window and need for close monitoring limited their use. Direct oral anticoagulants (DOACs) offered safer, more convenient alternatives, backed by robust phase III trials. This thesis examines key concerns that arose after their approval and widespread use in clinical practice.
Part I reviews nonadherence and treatment patterns. Tracing the history of anticoagulant trials, we see how DOACs became the preferred agents. Large cohort studies reveal a clinician preference for factor Xa inhibitors, show that switching and serious nonadherence are relatively uncommon, and identify candidate predictors for both outcomes.
Part II focuses on higher-risk patients and off-label dosing. We found sex differences in how clinicians assess frailty using clinical judgment alone. Patients with atrial fibrillation and atherosclerotic disease in routine practice show better cardiovascular health and fewer events than those in original trials — likely due to patient selection, improved care, or tailored treatment. We critique flawed off-label dosing studies and recommend integrating clinical judgment into DOAC dosing decisions for higher-risk individuals. Finally, we show that higher event rates seen with apixaban in daily practice mainly reflect patients’ underlying risk, not off-label dosing.
Part III is on drug-level monitoring. We updated DOAC on-therapy ranges to aid interpretation of measured levels, and we found that a single apixaban measurement may help personalize dose selection.