A risk model can identify patients with heart failure and preserved ejection fraction (HFpEF) without atrial fibrillation (AF) who have an increased risk for stroke, according to a study in Circulation: Heart Failure.

Investigators sought to determine the rate of stroke in patients with HFpEF and to validate a stroke prediction model in patients with HFpEF without AF using pooled data from the I-Preserve (ClinicalTrials.gov Identifier: NCT00095238) and PARAGON-HF (ClinicalTrials.gov Identifier: NCT01920711) trials.

The researchers applied a previously validated risk model for stroke that included history of a previous stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide measurement at baseline.

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A total of 3798 patients (42.6%) with AF and 5126 patients without AF were included in the pooled dataset. The patients without AF had a mean age of 70.9±7.8 years, and 58.4% were women. Among the patients with AF, the median follow-up was 3.1 years and 5.4% had a stroke (17.2 per 1000 patient-years).

For patients without AF, the median follow-up was 3.6 years and 3.7% had a stroke (10.5 per 1000 patient-years). The 1-, 2-, and 3-year cumulative incidence function (CIF) stroke rates were 1.1% (95% CI, 0.8%-1.4%), 2.0% (95% CI, 1.7%-2.5%), and 2.9% (95% CI, 2.5%-3.5%), respectively.

In the highest tertile, the 1-, 2- and 3-year CIF rates of stroke were 1.8% (95% CI, 1.3%-2.6%), 3.4% (95% CI, 2.6%-4.5%), and 4.6% (95% CI, 3.7%-5.8%), respectively. In risk tertile 3, patients had a stroke rate of 17.7 per 1000 patient-years.

According to Cox proportional hazard models, stroke risk increased as the risk score increased: tertile 2 (hazard ratio [HR], 1.78; 95% CI, 1.17-2.71); tertile 3 (HR, 3.03; 95% CI, 2.06-4.47), with tertile 1 as a reference.

The observed and predicted stroke probabilities at 1, 2, and 3 years were compared among patients divided by tertiles and were acceptable. Model discrimination was good, with an overall C index of 0.81 (95% CI, 0.68-0.91). The S2I2N0-3 score discrimination for stroke also was good, with an overall C index of 0.86 (95% CI, 0.73-0.95).

Among the patients without AF who had stroke, compared with those who had no stroke, the risk of death increased markedly. The all-cause mortality rate was 4.0 (95% CI, 3.7-4.3) per 100 patient-years in patients with no stroke compared with 27.8 (95% CI, 22.1-35.0) per 100 patient-years in patients after a stroke, for an HR of 6.90 (95% CI, 5.32-8.95).

Among several limitations, the 2 large clinical trials used in the analyses had specific inclusion/exclusion criteria and likely included patients with a lower risk than occurs in the real world. Also, the investigators do not distinguish between type 1 and type 2 diabetes, although most patients with HFpEF have type 2 diabetes. In addition, ischemic and hemorrhagic stroke are not differentiated.

“…we confirmed that patients with HFpEF can have a substantial risk of stroke even in the absence of AF and validated a risk model for stroke in patients with HFpEF without AF,” wrote the researchers. “The balance of risk-to-benefit in these individuals may justify the use of prophylactic anticoagulation. This hypothesis needs to be evaluated in a prospective randomized controlled trial.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Kondo T, Jering KS, Jhund PS, et al. Predicting stroke in heart failure and preserved ejection fraction without atrial fibrillation. Circ Heart Fail. Published online June 23, 2023. doi: 10.1161/CIRCHEARTFAILURE.122.010377

This article originally appeared on The Cardiology Advisor