Prothrombin Time-International Normalized Ratio Predicts the Outcome of Atrial Fibrillation Patients Taking Rivaroxaban

Figure 1. Enrollment of patients with non-valvular atrial fibrillation with baseline prothrombin time-international normalized ratio (PT-INR) available after taking direct oral anticoagulants (DOACs). From 1 June 2012 to 30 September 2018, a total of 5541 and 2274 patients diagnosed with non-valvular AF taking rivaroxaban or dabigatran were identified. The study finally identified a total of 3192 patients taking rivaroxaban and 958 patients taking dabigatran with PT-INR and aPTT available, respectively. aPTT = activated partial thromboplastin time; DOACs = direct oral anticoagulants; PT-INR = prothrombin time-international normalized ratio.

Figure 2. Factors associated with an INR ≥ 1.5 for patients treated with rivaroxaban. The multivariate analysis indicated that the “on-label” prescription following the ROCKET AF or J-ROCKET AF dose criteria and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban, while patients with a higher HAS-BLED score, the presence of underlying diabetes mellitus, higher hemoglobin and eGFR, and use of diltiazem were independent factors associated with an INR < 1.5 after taking rivaroxaban. CHA2DS2-VASc = congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 years, female; CI = confidence interval; eGFR = estimated glomerular filtration rate; HAS-BLED = hypertension, abnormal renal or liver function, stroke, bleeding history, labile INR, age 65 years or older, and antiplatelet drug or alcohol use; INR = international normalized ratio; NVAF = non-valvular atrial fibrillation; OR = odds ratio.

Figure 3. Cumulative incidence curves of IS/SE and major bleeding for AF patients treated with rivaroxan with different INR categories. Thromboembolic events appeared to be lower in patients with an INR ≥ 1.5 compared to other groups (p = 0.04), while the risk of major bleeding was not significantly different between four groups (p = 0.77). AF = atrial fibrillation; INR = international normalized ratio; IS/SE = ischemic stroke/systemic embolism.

Figure 4. Risks of IS/SE and major bleeding for 3192 AF patients treated with rivaroxaban with different INR. Among 3192 patients treated with rivaroxaban, there were 643 (20.1%) patients having an INR ≥ 1.5. Compared to patients with an INR < 1.1, patients with an INR ≥ 1.5 were associated with a lower risk of IS/SE and were not associated with a higher risk of major bleeding. aHR = adjusted hazard ratio; CI = confidential interval; INR = international normalized ratio; IS/SE = ischemic stroke/systemic embolism; PT = prothrombin time.

Figure 5. Risks of IS/SE and major bleeding for 3192 AF patients treated with on-label dosing of rivaroxaban with different INR levels. Among 2203 patients treated with rivaroxaban, compared to patients with an INR < 1.1, patients with an INR ≥ 1.5 were associated with a lower risk of IS/SE and were not associated with a higher risk of major bleeding. aHR = adjusted hazard ratio; CI = confidential interval; INR = international normalized ratio; IS/SE = ischemic stroke/systemic embolism; PT = prothrombin time.

Figure 6. Risks of IS/SE and major bleeding for 958 AF patients treated with dabigatran with different aPTT ratio levels. For patients treated with dabigatran, a higher aPTT ratio of 1.1–1.2 and 1.3–1.4 were associated with a lower risk of IS/SE than those with an aPTT ratio <1.1. A prolonged aPTT ratio was not associated with a higher risk of major bleeding. aPTT = activated partial thromboplastin time; CI = confidential interval; aHR = adjusted hazard ratio; IS/SE = ischemic stroke/systemic embolism; NVAF = non-valvular atrial fibrillation.