Predicting stroke in heart failure and reduced ejection fraction without atrial fibrillation

Area of Science:

• Cardiology
• Neurology
• Pharmacology

Background:

• Patients with heart failure with reduced ejection fraction (HFrEF) have a significantly elevated risk of stroke.
• Anticoagulant therapy can mitigate stroke risk in HFrEF patients, but its overall risk-benefit profile is unfavorable in those without atrial fibrillation (AF).

Purpose of the Study:

• To validate a simple risk model for identifying HFrEF patients without AF who are at the highest risk of stroke.
• To determine if a subset of HFrEF patients without AF exhibits a stroke risk comparable to AF patients not receiving anticoagulation.

Main Methods:

• A pooled patient-level analysis of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials was conducted.
• A previously derived risk model using prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide levels was validated in 20,159 patients, including 12,751 without baseline AF.
• Stroke events were analyzed in relation to the validated risk score.

Main Results:

• Among HFrEF patients without AF, 346 (2.7%) experienced a stroke over a median of 2.0 years (11.7 per 1000 patient-years).
• Stroke risk significantly increased with higher risk scores, with the highest quintile showing a hazard ratio of 3.73 compared to the lowest.
• Patients in the top risk quintile had a stroke rate of 21.2 per 1000 patient-years, similar to AF patients not on anticoagulation (20.1 per 1000 patient-years).
• The risk model demonstrated good discrimination (C-index 0.84).

Conclusions:

• A significant subset of HFrEF patients without AF can be identified as having a stroke risk equivalent to that of AF patients not receiving anticoagulation.
• For these high-risk individuals, the risk-benefit assessment may favor prophylactic anticoagulation, warranting prospective investigation.