Ayush Agarwal, DM
@drayushagarwal

Meya L, Polymeris AA, Schaedelin S, Schaub F, Altersberger VL, Traenka C, Thilemann S, Wagner B, Fladt J, Hert L, et al. Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others. Stroke. 2021.

Cardio-embolic strokes comprise one third of all acute ischemic strokes.1 Trials have proven direct oral anticoagulants (DOACs) to be as effective as vitamin K antagonists (VKAs) with lesser intracranial bleeding risk.2 The added absence of dietary interactions and routine blood level monitoring makes DOACs the preferred alternative over VKAs.3

However, all major DOAC trials recruited patients with only minor strokes and transient ischemic attacks, and patients with disabling strokes were excluded.4-7 This excluded population forms a significant proportion of stroke burden as approximately 40% of strokes attributable to atrial fibrillation (AF) are dependent on caregivers for their daily living.8

Meya et al. studied the safety and efficacy of DOACs compared to VKAs in strokes attributable to AF who were dependent on the daily help of others at discharge [modified Rankin Scale score (mRS): 3-5]. Their primary outcome was the composite of stroke recurrence, major bleeding and death from any cause. They recruited 801 cases, of which 391 were dependent (319- DOACs, 72-VKAs). They found that overall (801 patients), DOAC treated patients had a lower hazard for the composite outcome (HR=0.58; 95% CI: 0.42-0.81), and independent patients fared better than dependent ones (HR=0.54; 95% CI: 0.40-0.71). Kaplan-Meier curve for composite outcome showed that independent patients on DOACs did the best followed by independent patients on VKAs and dependent ones on DOACs; dependent ones on VKAs fared the worst. However, there was no evidence of any statistically significant difference in the effect of anticoagulant type (DOAC versus VKA) on the composite outcome between dependent patients in simple, adjusted and weighted models.

This study provides evidence that DOACs can be safely and effectively administered in cardio-embolic strokes with a discharge mRS 3-5. These findings can also provide the base for a future randomized controlled trial, the findings of which will conclusively prove this point.

References:

  1. Perera KS, Vanassche T, Bosch J, et al. ESUS Global Registry Investigators. Global survey of the frequency of atrial fibrillation-associated stroke: embolic stroke of undetermined source global registry. Stroke. 2016; 47:2197-2202
  2. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet. 2014;383:955-962.
  3. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardiothoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2021; 42:373-498.
  4. Diener HC, Connolly SJ, Ezekowitz MD, et al; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010;9:1157-1163.
  5. Easton JD, Lopes RD, Bahit MC, et al; ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: a sub-group analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11:503-511.
  6. Hankey GJ, Patel MR, Stevens SR, et al; ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012; 11:315-322.
  7. Rost NS, Giugliano RP, Ruff CT, et al; ENGAGE AF-TIMI 48 Investigators. Outcomes with edoxaban versus warfarin in patients with previous cerebrovascular events: findings from ENGAGE AF-TIMI 48. Stroke. 2016; 47:2075-2082.
  8. Yoshimura S, Koga M, Sato S, et al; SAMURAI Study Investigators. Two-year outcomes of anticoagulation for acute ischemic stroke with nonvalvular atrial fibrillation- SAMURAI-NVAF study. Circ J. 2018; 82:1935-1942.