Treatment with oral anticoagulation is associated with a significantly lower incidence of stroke in patients with heart failure with reduced ejection fraction (HFrEF) or atrial fibrillation (AF), according to research findings published in Stroke.

Although current guidelines recommend oral anticoagulation to reduce the risk of stroke in patients with AF, this form of therapy has not consistently demonstrated superiority over antiplatelet therapy for preventing cardiovascular events in patients with HFrEF.

In a meta-analysis, researchers sought to further clarify the role of oral anticoagulation for preventing ischemic stroke in patients with AF and HFrEF. The analysis included 21 randomized clinical trials that compared patients using oral anticoagulation with a control group. A total of 19,332 patients had AF (mean follow-up, 23.1 months) and 9866 patients had HFrEF (mean follow-up, 23.9 months).


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The incidence of stroke was the study’s primary outcome, whereas secondary outcome measures included the incidence of ischemic stroke, hemorrhagic stroke, mortality, myocardial infarction (MI), and major hemorrhage.

In all 21 trials, a total of 1113 stroke events occurred during follow up, including 339 in the pooled oral anticoagulation arm and 774 in the control group. Compared with control, oral anticoagulation was associated with a significant reduction in all stroke over a mean study follow-up period of 1.92 years (2.8% vs 5.8%; odds ratio [OR], 0.54; 95% CI, 0.46-0.63; absolute risk reduction [ARR], 2.1%; 95% CI, 2% to 2.5%).

In the 18 studies that reported 846 ischemic stroke events, the use of oral anticoagulation was associated with a significant reduction in ischemic stroke compared with control group outcomes (1.9% vs 5.2%, respectively; OR, 0.46; 95% CI, 0.38-0.54; ARR, 2.1%; 95% CI, 2% to 2.5%).

In 16 studies that reported 79 hemorrhagic strokes, oral anticoagulation was not associated with an increase in hemorrhagic stroke compared with control group outcomes (0.29% vs 0.19%; OR, 1.23; 95% CI, 0.76-1.99; absolute risk increase [ARI], 0.068%; 95% CI, 0.067% to -0.2%).

In contrast, the use of oral anticoagulation was not associated with reduced all-cause mortality compared with control group outcomes in the pooled analysis (11% vs 12%, respectively; OR, 0.95; 95% CI, 0.88-1.02; ARR, 0.57%; 95% CI, -0.2% to 1.3%).

In terms of MI, use of oral anticoagulation showed superiority over the control group for reducing MI rates (2.2% vs 2.9%; OR, 0.83; 95% CI, 0.71-0.98; ARR, 0.42%; 95% CI, 0.06% to 0.78%).

The use of oral anticoagulation across 17 studies was associated with an increase in major hemorrhage (3.4% vs 2.1%; OR, 1.53; 95% CI, 1.08-2.16; ARI, 0.85%; 95% CI, 0.45% to 1%). Despite this increase, oral anticoagulation was not associated with an increased risk of fatal hemorrhage in patients with either AF or HFrEF.

A limitation of this analysis was the inclusion of studies that varied in regard to their international normalized ratio (INR) targets. The studies also varied in their definitions of major hemorrhage.

The researchers added that the “differences in the primary outcomes employed by trials in HFrEF, compared with AF, may have contributed to differing conclusions of the relative efficacy of oral anticoagulation, particularly the inclusion of all-cause mortality in most HFrEF trials.”

Reference

Reddin C, Judge C, Loughlin E, et al. Association of oral anticoagulation with stroke in atrial fibrillation or heart failure: a comparative meta-analysis. Stroke. Published online July 20, 2021. doi:10.1161/STROKEAHA.120.033910