Association Between Direct Oral Anticoagulant Score and Bleeding Events in Patients With Atrial Fibrillation Following Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Cohort Study

Abstract

Background: The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement.

Methods and results: This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate- (≤7 points), high- (8-9 points), and very high-risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate-, high-, and very high-risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3-year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P<0.01). Multivariable Cox regression analysis revealed that significant increments in the DOAC Score were associated with a risk of all bleeding events at 3 years in the overall cohort (hazard ratio [HR], 1.22 [95% CI, 1.08-1.38]; P<0.01), in the DOAC cohort (HR, 1.20 [95% CI, 1.01-1.42]; P=0.04), and in the vitamin K antagonist cohort (HR, 1.25 [95% CI, 1.04-1.50]; P=0.02).

Conclusions: The DOAC Score was significantly associated with bleeding events in patients with atrial fibrillation after transcatheter aortic valve replacement, aiding in clinical decision-making for anticoagulant management.

Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023585; Unique identifier: UMIN000020423.

Keywords: DOAC Score; atrial fibrillation; bleeding; transcatheter aortic valve replacement.

Figure 1. Kaplan‐Meier curves showing the cumulative incidence of all bleeding events in the 3 populations.

The overall population (A), DOAC cohort (B), and VKA cohort (C) demonstrate a significant difference in the incidence of all bleeding events at 3 years among the 3 DOAC Score risk groups (P<0.01, P=0.02, P=0.04, respectively). DOAC indicates direct oral anticoagulant; TAVR, transcatheter aortic valve replacement; and VKA, vitamin K antagonist.

Figure 2. Kaplan‐Meier curves showing the cumulative composite end point of all bleeding events and all‐cause death in the 3 cohorts.

Cumulative composite end point of all bleeding events and death at 3 years is significantly different among the 3 DOAC Score risk groups in the overall population (P<0.01) (A) and VKA cohort (P<0.01) (C), but not in DOAC cohort (P=0.09) (B). DOAC indicates direct oral anticoagulant; TAVR, transcatheter aortic valve replacement; and VKA, vitamin K antagonist.

Figure 3. Comparison of discriminating ability between the DOAC Score and HAS‐BLED Score.

Time‐dependent ROC curves for bleeding events at 3 years of the DOAC Score and HAS‐BLED Score were demonstrated. In comparison to the AUC using the IPCW method, the DOAC Score showed a significantly higher concordance statistic than that of the HAS‐BLED Score in the overall population (AUC 0.592 vs 0.509, adjusted P value=0.04, but not in the DOAC cohort (AUC 0.581 vs 0.533, adjusted P=0.74) or the VKA cohort (0.602 vs 0.551, adjusted P=0.57). AUC indicates area under the curve; DOAC Score, Direct Oral Anticoagulant Score; HAS‐BLED, Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly; IPCW, inverse probability of censoring weights; ROC, receiver operating characteristic; and VKA, vitamin K antagonist.