J Stroke Cerebrovasc Dis. 2013 Jul;22(5):620-6.

Identifying a high stroke risk subgroup in individuals with heart failure.

Pullicino PM, McClure LA, Howard VJ, Wadley VG, Safford MM, Meschia JF, Anderson A, Howard G, Soliman EZ.

KentHealth, University of Kent, Canterbury, United Kingdom. P.Pullicino@kent.ac.uk



BACKGROUND: Heart failure (HF) is associated with an overall stroke rate that is too low to justify anticoagulation in all patients. This study was conducted to determine if vascular risk factors can identify a subgroup of individuals with heart failure with a stroke rate high enough to warrant anticoagulation.

METHODS: The REGARDS study is a population-based cohort of US adults aged ≥45 years. Participants are contacted every 6 months by telephone for self- or proxy-reported stroke and medical records are retrieved and adjudicated by physicians. Participants were characterized into 3 groups: HF without atrial fibrillation (AF), AF with or without HF, and neither HF nor AF. Cardiovascular risk factors at baseline were compared between participants with and without incident stroke in HF and AF. Stroke incidence was assessed in risk factor subgroups in HF participants.

RESULTS: Of the 30,239 participants, those with missing/anomalous data were excluded. Of the remaining 28,832, 1360 (5%) had HF without AF, 2528 (9%) had AF, and 24,944 (86%) had neither. Previous stroke/transient ischemic attack (TIA; P = .0004), diabetes mellitus (DM; P = .03), and higher systolic blood pressure (P = .046) were associated with increased stroke risk in participants with HF without AF. In participants with HF without AF, stroke incidence was highest in those with previous stroke/TIA and DM (2.4 [1.1, 4.0] per 100 person-years).

CONCLUSIONS: The combination of previous stroke/TIA and DM increases the incidence of stroke in participants with HF without AF. No analyzed subgroup had a stroke rate high enough to make it likely that the benefits of warfarin would outweigh the risks.

Published by Elsevier Inc.

PMID: 22142776



Like the dysfunctional left atrial appendage, the dilated left ventricle appears to be a site of thrombus formation. Cardioembolism is likely the main pathogenesis of stroke in heart failure (HF), as it is in atrial fibrillation (AF).  Warfarin is used widely to prevent stroke in both conditions, but clear scientific underpinning for this use is available only for AF. The role of warfarin in the prevention of stroke in AF is clearly defined. Multiple prospective randomized clinical studies have shown that warfarin reduces the risk of stroke in AF1 and have provided a clear understanding of the risk factors for stroke in AF. We also know the risk reduction that can be obtained when balancing warfarin’s effect on stroke reduction and central nervous system hemorrhage, which allows selection of a population at high risk for stroke, in whom warfarin’s benefits outweigh its risks.2 Current guidelines4 recommend anticoagulation in moderate to high risk patients with AF (CHADS2 score 2-3 who have thromboembolic rates of 5.27 [4.15-6.70] to 6.02 [3.90-9.29] patient years3) and also in all AF patients with stroke or TIA (with thromboembolic rates of 7.4 to 10.8 per 100 patient years).

The recent Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial5 has shown that warfarin has a similar risk reduction effect in HF in sinus rhythm as in AF, with a hazard ratio for stroke of 0.52 (0.33-0.82) with warfarin versus aspirin. AF guidelines do not apply to HF in sinus rhythm however, as the overall rate of stroke in HF (0.7 -1.5% per year) is about one-third of that in AF.  The current study was an attempt to look for high stroke risk subgroups in patients with HF in sinus rhythm. The highest stroke rates found were 1.3 (0.47-2.5) per hundred patient years in patients with HF and stroke or TIA and 2.4 (1.1-4.0) per hundred patient years in patients with HF, stoke or TIA and diabetes. These rates are too low to give a large enough clinical benefit to justify anticoagulation with warfarin in these subgroups.

There are still likely to be patients with HF in sinus rhythm who do have a high enough stroke risk to justify warfarin anticoagulation. This study did not use ejection fraction or other echocardiographic  risk factors that may be important for defining subgroups with higher stroke risk and these need to be studied. The stroke rate of 0.69 per hundred patient years found in this study may underestimate the stroke risk in clinical HF populations. Further studies are needed to confirm the recurrent stroke rate in HF patients with stroke or TIA.  Thrombin inhibitors such as dabigatran should be studied in HF in sinus rhythm since current guidelines4 recommend their use in AF with a single risk factor (thromboembolic rate 2.5 [1.98-3.15] per hundred patient years). This rate is similar to the rate of stroke in HF patients with stroke/TIA and diabetes in the current study and potentially gives a subgroup in which thrombin inhibitors might be clinically justified.

  1. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: Analysis of pooled data from five randomized controlled trials. Arch Int Med 1994;1449-1457.
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  3. Go AS, Hylek EM, Chang Y, et al.  Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA 2003;290:2685–2692.
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  5. Homma S, Thompson JLP, Pullicino PM et al. Warfarin and aspirin in patients with heart failure in sinus rhythm. NEJM 2012;366:1859-1869.
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