Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials

Azmil H Abdul-Rahim, Ana-Cristina Perez, Rachael L MacIsaac, Pardeep S Jhund, Brian L Claggett, Peter E Carson, Michel Komajda, Robert S McKelvie, Michael R Zile, Karl Swedberg, Salim Yusuf, Marc A Pfeffer, Scott D Solomon, Gregory Y H Lip, Kennedy R Lees, John J V McMurray, Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity-Preserved (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function (I-Preserve) Steering Committees, Azmil H Abdul-Rahim, Ana-Cristina Perez, Rachael L MacIsaac, Pardeep S Jhund, Brian L Claggett, Peter E Carson, Michel Komajda, Robert S McKelvie, Michael R Zile, Karl Swedberg, Salim Yusuf, Marc A Pfeffer, Scott D Solomon, Gregory Y H Lip, Kennedy R Lees, John J V McMurray, Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity-Preserved (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function (I-Preserve) Steering Committees

Abstract

Aims: The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF.

Methods and results: We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively).

Conclusions: A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.

Keywords: Heart failure with preserved ejection fraction; Risk-factors; Stroke.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Kaplan–Meier plot stroke for chronic heart failure patients with preserved ejection fraction according to atrial fibrillation status at baseline. AF, atrial fibrillation.
Figure 2
Figure 2
The relationship between baseline variables and risk of stroke in patients with heart failure and preserved ejection fraction without atrial fibrillation. Variables are divided by quintiles. BMI, body mass index; BP, blood pressure; LV, left ventricular; NT-proBNP, N-terminal pro-B-type natrieretic peptide.
Figure 3
Figure 3
Distribution of risk score for stroke and its relation to predicted risk of stroke within the follow-up period.
Figure 4
Figure 4
Kaplan–Meier plot for stroke according to tertile of risk score in patients without atrial fibrillation.
Figure 5
Figure 5
Comparison of observed and expected stroke rates after 3 years for patients categorized by tertile of risk-score derived from the heart failure with reduced ejection fraction stroke model. Observed shows the 3 year Kaplan–Meier rate for each tertile; expected shows estimate from the Cox model for each tertile.

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