Prognostic Value of INR Fluctuations during Anticoagulant Therapy in Patients with Atrial Fibrillation and a High Thromboembolic Risk

Background: Anticoagulation therapy with vitamin K agents needs regular monitoring to maintain the International Normalized Ratio (INR) within the recommended target range (2–3) for an appropriate benefit to risk ratio in patients with atrial fibrillation. Still, INR fluctuates greatly with time, even with the same dose for a given patient. Objective: The purpose of our analysis was to try to identify the possible factors participating in INR fluctuations and to study whether INR instability affects the occurrence of thromboembolic and hemorrhagic events in clinical practice. Methods: We studied INR data of 157 patients participating in a prospective anticoagulant (fluindione) and aspirin association in patients with high-risk atrial fibrillation trial [Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontane (FFAACS) study]. During the first year of follow-up, INR variability was assessed by four different parameters. Logistic regression models were performed to assess the predictive power of INR variability recorded during the first year and its relationship with the occurrence of thromboem bolic and bleeding events during the 5 years of follow- up. Results: No clinical or biological parameter studied was significantly associated with INR variability in this population. No INR variability parameter was significantly predictive of thromboembolic events. In contrast, patients with greater difference between the maximal and the minimal registered INR values and INR variability over time had a significantly higher incidence of any hemorrhagic complication (odds ratios of 2.6 and 1.9, respectively) during follow-up. Conclusions: Large fluctuations of the INR are an important factor to take into account for the bleeding risk in patients with atrial fibrillation with a high thromboembolic risk receiving oral anticoagulation therapy.