Large majority of AF patients who suffered from stroke were not adequately anticoagulated

Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation

Literature - Xian Y, O’Brien EC, Liang L et al., - JAMA. 2017;317(10):1057-1067. doi:10.1001/jama.2017.1371


Although the burden of atrial fibrillation (AF)-associated stroke risk is high, AF is a treatable risk factor for stroke. It is well documented that anticoagulants such as vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) reduce stroke risk in AF patients. Current guidelines therefore recommend adjusted-dose warfarin (a VKA) or NOACs for stroke prevention in high-risk patients with AF.

Oral anticoagulants are often underused in community practice [1,2]. Little is known about the prevalence of preceding antithrombotic treatment among AF patients who develop acute ischemic stroke and whether this therapy affects stroke severity and outcomes.

This study therefore examined preceding antithrombotic therapy in patients with AF who have experienced an acute ischemic stroke, and the association between treatment and initial stroke severity, in-hospital mortality and functional outcomes at discharge. This analysis was part of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study [2-6]. PROSPER builds on the American Heart Association (AHA)/American Stroke Association (ASA) Get With the Guidelines–Stroke (GWTG-Stroke) Registry program. This retrospective analysis included data of patients (n=94474, admitted to 1622 hospitals, mean age : 79.9 years, SD: 11.0) with a known history of AF or atrial flutter who experienced an acute ischemic stroke and were admitted from October 2012 through March 2015. The NIHSS score was used as a measure of stroke severity (range of 0-42, with a higher score indicating greater stroke severity).

Main results

  • 79008 (83.6%) of included patients were not receiving therapeutic anticoagulation prior to stroke, 7176 (7.6%) received therapeutic warfarin and 8290 (8.8%) were receiving NOACs.
  • Of patients not receiving adequate therapeutic anticoagulation, 12751 (13.5%) had a subtherapeutic warfarin with INR <2 at the time of stroke, 37674 (39.9%) were receiving antiplatelet therapy only, and 28583 (30.3%) were not receiving any antithrombotic treatment prior to stroke.
  • Median initial NIHSS score was higher in patients not receiving antithrombotic medication (7, IQR: 2-16), and those receiving antiplatelet therapy only (6, IQR: 2-15), or subtherapeutic warfarin (6, IQR: 2-16), as compared with those receiving therapeutic warfarin (4, IQR: 1-10) and NOACs (4, IQR: 1-11, P<0.001).
  • Therapeutic warfarin (adjOR: 0.56, 95%CI: 0.51-0.60), NOACs (adjOR: 0.65, 95%CI: 0.61-0.71) and antiplatelet therapy only (adjOR: 0.88, 95%CI: 0.84-0.92) reduced the odds of moderate or severe stroke, as compared with no antithrombotic treatment.
  • Adj odds of in-hospital mortality was lower in those on therapeutic warfarin (adOR: 0.75, 95%CI: 50.67-0.85), NOACs (AdjOR: 0.79, 95% CI: 0.72-0.88), and antiplatelet therapy only (AdjOR= 0.83, 95%CI: 0.78-0.88) as compared with no antithrombotic treatment.
  • Except for age and antiplatelet therapy, prior stroke and NOACs, and CHA2DS2-VASc score and subtherapeutic warfarin with respect to stroke severity, no significant interactions were seen for subgroups. Regarding mortality, significant interactions were seen for sex and subtherapeutic warfarin, prior stroke and therapeutic warfarin and CHA2DS2-VASc and antiplatelet were seen.
  • Patients who had received antithrombotic therapy had higher odds of having better functional outcomes at discharge than those without any preceding antithrombotic therapy (mRS score of 0-1 [excellent recovery] or 0-2 [functional independence]).


In this nationwide, contemporary registry of patients with a known history of AF who had experienced an acute ischemic stroke, 84% did not receive guideline-recommended anticoagulation or had subtherapeutic anticoagulation levels. This affects clinical outcomes, as preceding coagulation with NOACs or therapeutic warfarin was associated with less severe stroke and fewer deaths during the hospital stay.


1. Meschia JF, Bushnell C, Boden-Albala B, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Functional Genomics and Translational Biology; Council on Hypertension. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-3832.

2. Waldo AL, Becker RC, Tapson VF, Colgan KJ; NABOR Steering Committee. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J AmColl Cardiol. 2005;46(9):1729-1736.

3. Hannah D, Lindholm B, Maisch L. Certain uncertainty: life after stroke from the patient’s perspective. Circ Cardiovasc Qual Outcomes. 2014;7 (6):968-969.

4. Xian Y, O’Brien EC, Fonarow GC, et al. Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research: implementing the patient-driven research paradigm to aid decision making in stroke care. Am Heart J. 2015;170(1):36-45, e1-e45.

5. Xian Y,Wu J, O’Brien EC, et al. Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. BMJ. 2015;351:h3786.

6. O’Brien EC, Greiner MA, Xian Y, et al. Clinical effectiveness of statin therapy after ischemic stroke: primary results from the statin therapeutic area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. Circulation. 2015;132 (15):1404-1413.

Find this article online at JAMA

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free