Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.

Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.

Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1).

Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88.

Conflict of interest statement

MP: speaker honoraria from Sanofi‐Aventis, Boehringer‐Ingelheim, Bayer, BMS, Daiichi‐Sankyo, Pfizer (all manufacturers of anticoagulants). MK: speaker honoraria from Bayer, Nippon Boehringer‐Ingelheim, Daiichi‐Sankyo. MC: consulting fees from Boehringer‐Ingelheim, Pfizer/BMS; advisory board Daiichi‐Sankyo. GMDM: consultant/speaker honoraria from Bayer, travel honoraria from Pfizer. ST: travel grants from BMS/Pfizer. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer‐Ingelheim and Daiichi‐Sankyo; no fees are received personally. LHB: consultancy or advisory board fees or speaker's honoraria from Bayer and BMS. PAL: research grants from Bayer, travel grants from Bayer, Pfizer, advisory board compensation from Bayer, Pfizer, Daiichi‐Sankyo, BMS. KT: lecture honoraria (modest) from Daiichi‐Sankyo, Bayer Yakuhin, Nippon Boehringer‐Ingelheim, BMS. DJW: personal fees from Bayer, Portola (manufacturer of the anticoagulant reversal agent andexanet alfa). STE: research support from Pfizer, Daiichi‐Sankyo; compensation from Stago (manufacturer of coagulation testing systems) for educational material; travel/speaker honoraria from Bayer, Boehringer‐Ingelheim, BMS, Daiichi‐Sankyo; advisory board Bayer, Boehringer‐Ingelheim, BMS. The remaining authors declare no relevant conflicts.

© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Figures

FIGURE 1

Study Flowchart

FIGURE 2

Weighted Kaplan–Meier curves for the composite outcome stratified to anticoagulant type (DOAC / VKA) and age group (≥85 /

FIGURE 3

Hazard ratio estimates for the effect of DOAC vs. VKA on the primary composite outcome and all its individual components (accounting for competing risks) stratified to patients aged ≥85 versus

FIGURE 4

Net clinical benefit of DOAC over VKA with 95% confidence intervals stratified to age group (≥85 /

FIGURE 5

Rate of the composite outcome by age as a continuous variable stratified to type of anticoagulant (DOAC / VKA). The solid lines represent the estimates for each year of age from the weighted model without interaction term and the shaded areas the 95%‐CI.