AMSTERDAM – The presence of three or more ischemic stroke risk factors in patients with no history of atrial fibrillation or stroke spells high stroke risk, comparable with that seen in patients who do have atrial fibrillation, according to a Danish national study.
Moreover, individuals with five or more stroke risk factors have essentially the same high stroke risk – roughly 8% per year – regardless of whether they have a history of atrial fibrillation (AF) or not, Dr. Christine Benn Christiansen reported at the annual congress of the European Society of Cardiology.
"The stroke risk increases with the number of risk factors. This has not been shown before in patients without prior stroke or atrial fibrillation," said Dr. Christiansen of Gentofte Hospital, Hellerup, Denmark.
"The main message here is there’s a great potential for reducing stroke risk in patients without atrial fibrillation," she added.
The impetus for the Danish national study lies in the fact that 80% of ischemic strokes occur in individuals without AF. The majority of these are first-time strokes. Yet the well-known guideline-recommended stroke-risk scores CHADS2 and CHA2DS2-VASc apply only to patients with AF.
"In patients without prior stroke, without AF, there is no systematic risk approach to deciding whether such people should receive any kind of antithrombotic medication to prevent ischemic strokes," Dr. Christiansen observed.
She and her coinvestigators analyzed comprehensive Danish national health care registries and identified 4.2 million adult Danes with no history of stroke. The investigators then followed these subjects, including 31,716 with a baseline diagnosis of AF, through the registries for 11 years, during which 130,336 patients were diagnosed with new-onset AF. The main goal was to compare 11-year stroke rates between patients with and without baseline AF based upon the number of stroke risk factors present.
The investigators cast a wide net in terms of stroke risk factors. They included epilepsy, heart failure, chronic systemic inflammatory conditions, hypertension, chronic renal disease, prior MI, diabetes, and peripheral artery disease. They also took into account venous thromboembolism, migraine, arterial embolism, carotid stenosis, and retinal vascular occlusion.
The stroke rate in subjects without baseline AF maxed out at 7.27 cases per 100 patient-years, or 7.27% annually, with five or more stroke risk factors present. Notably, the stroke rate was similar at 8.0% per year in patients with five or more baseline stroke risk factors plus AF (see graph).
ESC spokesperson Dr. Güenter Breithardt, emeritus professor of medicine at the University of Münster (Germany), said that he suspects the mechanism underlying the high stroke rate seen in patients with large numbers of stroke risk factors but no AF is that many of these individuals actually had silent AF that went unrecognized. Many of these stroke risk factors are also risk factors for development of AF, he observed.
Arguing against that hypothesis, Dr. Christiansen replied, is that each of the stroke risk factors as well as the development of AF were analyzed as time-dependent variables adjusted for age, gender, and the remaining stroke risk factors. Thus, patients with silent and unrecognized AF at baseline whose arrhythmia became symptomatic and got diagnosed during 11 years of follow-up were removed from the no-baseline-AF group for the data analysis, she said.
Dr. Harry Crijns, session cochair, summarized the central study findings as follows: "For patients who do not have a lot of accumulated risk factors, the additional presence of atrial fibrillation has a significant impact. On the other hand, in patients who have a lot of risk factors, atrial fibrillation doesn’t seem to have an impact. However, I would say searching for atrial fibrillation in such patients might differentiate a subgroup with even higher risk, although that wasn’t looked at in this study. That would be a good topic for future research."
In an interview, he said he doesn’t consider the Danish results practice changing. Patients with a large accumulation of the stroke risk factors used in the study, especially patients with established vascular disease, should already be on daily aspirin, yet at this point the Danish investigators aren’t able to say how many such patients were. However, he granted that in everyday practice today many such patients aren’t on aspirin, which is how the organizers of the ongoing, 5-year ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) trial were able to enroll roughly 12,000 high-risk patients who weren’t on aspirin to randomize them to daily aspirin or placebo.
No expert would recommend oral anticoagulant therapy for stroke prevention in patients without AF or prior stroke at this time, no matter how many stroke risk factors they have, because there are as yet no randomized trial data to support such a step. There will need to be evidence that the preventive benefit outstrips the increased bleeding risk.