Risk Model May Predict Stroke in Patients With HFpEF Without AF

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 investigators 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.

A total of 3798 patients (42.6%) with AF and 5126 patients without AF were included in the pooled dataset. The patients without AF were a mean (SD) 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 S₂I₂N_0-3 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 for 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.

“… [W]e 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 investigators. “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.

This article originally appeared on The Cardiology Advisor