Peggy Nguyen, MD

Adelborg K, Szépligeti S, Sundbøll J, Horváth-Puhó E, Henderson VW, Ording A, et al. Risk of Stroke in Patients With Heart Failure: A Population-Based 30-Year Cohort Study. Stroke. 2017

Heart failure has previously been identified in association with ischemic stroke, with previous literature citing thrombus formation, hypercoagulable state, endothelial dysfunction and impaired cerebral autoregulation as possible mechanisms underlying ischemia. Additionally, heart failure and stroke share several common etiological conditions, including hypertension and dyslipidemia (Stroke. 2011;42:2977-2982). However, the association between heart failure and hemorrhagic stroke, and the long-term implications of heart failure on all-stroke risk, remained to be clearly elucidated. Here, patients with heart failure (n = 289,353) were compared to an age and gender matched control group (n = 1,446,765), for the outcomes of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) evaluated at 30 days, 1 year, and 30 years, providing a far more extensive follow up than previous studies.

At baseline, patients with heart failure had a higher prevalence of cardiac and noncardiac comorbidities than their matched controls, including hypertension, dyslipidemia, obesity, diabetes, and chronic kidney disease. Compared to their matched cohort, patients with heart failure had a higher absolute risk of ischemic stroke in the first 5 years, and a similar absolute risk of hemorrhagic stroke (both ICH and SAH). After 5 years, the absolute risk of all strokes, ischemic and hemorrhagic, were increased in the control group due to competing mortality.  However, the adjusted stroke rate ratios (aSRR) for ischemic and hemorrhagic stroke were elevated for the heart failure group at all follow up points. For ischemic stroke, the 30-day aSRR was 5.08, at 31–365 days was 2.08, and at 10–30 years was 1.54. For hemorrhagic stroke, the 30-day aSRR was 2.13 and 3.52 for ICH and SAH, respectively, and remained increased at 1.1 to 1.8-fold at 31 to 30 years follow up.

This study highlights the long-term association of heart failure with all stroke types, even up to 30 years from the index diagnosis of heart failure. Although the ischemic stroke risk does decrease with time, it remains elevated up to 3 decades out. Of course, this begs the question: If heart failure is an established strong risk factor for stroke, both ischemic and hemorrhagic, what might be the best therapy for primary stroke prevention? Even following sensitivity analyses adjusting for the use of anti-thrombotics, angiotensin-converting enzyme inhibitors, and beta blockers, the stroke risk remained persistently high in patients with heart failure.

Further studies evaluating primary stroke prevention therapies are needed for this cohort of high-risk patients. Previously published studies on anticoagulation for these patients have yielded mixed results. The WARCEF trial did not find a difference between aspirin and warfarin for the primary outcome of a composite end-point of ischemic stroke, ICH, or death from any cause; although the rate of ischemic stroke alone was significantly reduced in the warfarin group, the rate of hemorrhage was significantly higher in the anticoagulation group (N Engl J Med 2012; 366:1859-1869). Utilizing one of the novel oral anticoagulants (NOACs), some of which have a more favorable side effect profile, would seem to be an attractive alternative candidate therapy.