Smaller cerebral infarct size and no increase in microbleeds with NOAC vs. aspirin in AF
Effect of Apixaban on Brain Infarction and Microbleeds: AVERROES-MRI Assessment Study
O’Donnell M, Eikelboom J, Yusuf S, et al.
Am Heart J 2016; published online ahead of print
BackgroundIn dementia patients without a clinical history of acute stroke, neuroimaging often identifies the presence of cerebral infarction or hemorrhage, a situation called covert (subclinical) stroke [1,2]. Atrial fibrillation is a well-known risk factor for covert stroke, and in approximately 25% of AF patients covert brain infarction is discovered at routine MRI, often with an ‘embolic’ pattern [3-5]. Moreover, cerebral microbleeds on brain MRI are common in older adults and have been associated with an increased risk of intracerebral bleeding [6,7].
In the AVERROES trial in AF patients, NOAC apixaban reduced the risk of acute clinical ischemic stroke by 63% compared with aspirin, without increasing the risk of intracerebral hemorrhage . However, the effect of apixaban on covert stroke is not known.
In this substudy, brain MRIs in a subgroup of AVERROES participants were done to determine whether apixaban reduced the risk of the composite endpoint of symptomatic ischemic stroke and covert ‘embolic-pattern’ infarction and on microbleeds, as well as to explore the effect of apixaban on the progression of white matter hyperintensities. Mean interval from baseline to follow-up MRI scans was 1.0 year.
- Baseline MRI scans revealed brain infarct(s) in 26.2% (n=309/1180), microbleed(s) in 10.5% (n=99/940), covert ischaemic stroke in 20.5% (n=216/1054). Mean periventricular white matter intensity score was 3.0 (SD 2.4), mean subcortical ischaemic volume: 0.76ml (SD 1.9)
- The rate of the primary outcome was 2.0% in the apixaban group and 3.3% in the aspirin group (HR: 0.55; 95% CI: 0.27-1.14) from baseline to follow-up MRI scan.
- The rate of new infarction detected on MRI was 2.5% in the apixaban group and 2.2% in the aspirin group (HR: 1.09; 95% CI: 0.47-2.52), and the mean infarct diameter was 1.3cm in the apixaban group compared with 4.1cm in the aspirin group (P=0.03).
- On follow-up MRI there was no difference between treatment groups in proportion with new (or increase) in microbleeds (HR: 0.94; 95% CI: 0.50-1.76) and reduction in microbleeds (HR: 0.84; 95% CI: 0.56-2.03)(P=0.47 for net change in number of microbleeds between groups)
- Mean changes in periventricular white matter hyperintensity score were -0.06 (95% CI: 0.01-1.08), subcortical volume: +0.09ml (95% CI: 0.17-1.15ml) with no significant differences between treatment groups (P=0.64 and P=0.82 respectively).
ConclusionIn AF patients, apixaban, compared with aspirin, was associated with a non-significant trend toward reduction in the composite endpoint of clinical ischaemic stroke and covert embolic-pattern infarction. A reduction in the size of cerebral infarcts was seen with apixaban, and it did not increase the number of microbleeds. It should be noted that follow-up was short due to early termination of the AVERROES trial.
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