Vitamin K Antagonist Cessation and Stroke/TIA Risk in Newly Diagnosed AF

Discontinuation of vitamin K antagonist (VKA) oral anticoagulant therapy was associated with an elevated risk for stroke or transient ischemic attack (TIA) in patients newly diagnosed with nonvalvular atrial fibrillation (AF), according to study results published in the Journal of the American Heart Association.

Although thromboprophylaxis with a VKA is effective at preventing ischemic stroke/TIA in individuals with AF, therapy noncompliance may result in cerebrovascular accidents. Little is known about the risk for stroke or TIA or its temporal course following cessation of VKA therapy.

In this nested case-control analysis, the data from the 2001-2013 United Kingdom Clinical Practice Research Datalink database of 16,696 patients (age 45-89 years; mean age, 72.7 years; 57.5% men) with incident AF were examined. Study participants initiated VKA treatment within 60 days of diagnosis. The study’s primary outcome was a composite of community-acquired ischemic stroke or TIA (stroke/TIA). Participants with incident stroke/TIA were matched with control individuals without stroke/TIA.

Of a total of 514 patients with AF who had stroke/TIA, 489 were matched with 2137 control individuals. The mean CHA₂DS₂-VASc score was 4.3±1.7 in patients with AF and comparable in control individuals. The VKA cessation rates were 38.2% and 20.7% in patients with stroke/TIA and control individuals, respectively (relative risk [RR], 2.57; 95% CI, 2.01-3.28; adjusted excess incidence rate [IR], 1.75; 95% CI, 1.13-2.37 of additional strokes/TIAs per 100 person-years).

Of the 489 patients with AF who had stroke/AF, 223 participants (45.6%) and 266 (54.4%) had strokes/TIAs within and after 1 year of AF diagnosis, respectively. In the year following incident AF, patients who discontinued VKA treatment within 1 year had an adjusted RR for stroke/TIA of 2.45 (95% CI, 1.56-3.86), and an adjusted excess IR of stroke/TIA of 2.29 (95% CI, 0.98-3.90) per 100 person-years (ie, 1 stroke/TIA per 43 patients per year of VKA cessation).

Study strengths include a large sample size and closely matched controls. Study limitations include possible unmeasured confounding or hidden biases and possible underestimation of the association between stroke and VKA cessation.

“Increasing oral anticoagulant persistence, especially in the year after AF diagnosis, should be a therapeutic target to reduce stroke/TIA in AF,” noted the authors. They recommended that future research focus on maximizing VKA oral anticoagulant therapy compliance.

Disclosures: Dr Martinez, Dr Wallenhorst, and Dr Rietbrock report grants to the institution from Bayer, CSL Behring, Merz Pharma, and Bristol-Myers Squibb (significant), outside the submitted work. Dr Friedman reports grants to the institution, personal fees and nonfinancial support from Bayer, grants to the institution (significant), personal fees and nonfinancial support from Bristol-Myers Squibb–Pfizer (significant), personal fees and nonfinancial support from Daiichi Sankyo (modest), and nonfinancial support from Alivecor (modest), outside the submitted work.

Reference

Martinez C, Wallenhorst C, Rietbrock S, Freedman B. Ischemic stroke and transient ischemic attack risk following vitamin K antagonist cessation in newly diagnosed atrial fibrillation: a cohort study. J Am Heart Assoc. 2020;9(2):1-9. doi:10.1161/jaha.119.014376