Clinical InvestigationEffect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study
Section snippets
AVERROES trial
The study design and the main study methods and results have been previously reported.8,9 Patients were eligible if they had atrial fibrillation and at least 1 additional risk factor for stroke. Patients were required to be unsuitable for VKA therapy based on prior exposure (~50%), expectation of high bleeding risk or poor anticoagulant control, or patients’ preference. Patients were randomized to receive in blinded fashion apixaban 5 mg bid (2.5 mg bid in patients meeting 2 of the following 3
Sample size
Our original sample size was calculated based on the following considerations: (1) a proposed minimal risk reduction of approximately 50% for all “embolic” strokes (clinical stroke and embolic pattern on MRI) with apixaban compared with aspirin; (2) control event rate of symptomatic ischemic stroke of 4.2% per year in the aspirin group (based on recruitment of participants with CHADS2 score of ≥2) and a covert infarction rate of 11.7% per year, of which we anticipated that one-third would have
Results
In total, 1,185 participants were included in the MRI assessment study, and baseline MRI scans were received for 1,180 (99.6%), 601 participants in the apixaban group and 579 participants in the aspirin group. During follow-up, 29 participants died. Follow-up MRI scans were received for 931 (80.9%), and interpretable for analysis in 925 (80.4%) participants with baseline MRI scans and alive at time of final follow-up. In the entire cohort, follow-up MRI scans were completed in 79.8% in the
Discussion
Compared with aspirin, apixaban was associated with a trend toward a reduced risk of the composite of clinical stroke and covert “embolic” ischemic stroke. Although apixaban did not reduce the risk of any new infarction detected on routine MRI of brain, the size of infarcts was significantly smaller in the apixaban group compared with the aspirin group. Compared with aspirin, apixaban did not increase the burden of microbleeds on follow-up MRI. However, the event rate for new MRI-detected
References (24)
- et al.
Silent brain infarcts: a systematic review
Lancet Neurol
(2007) - et al.
Silent cerebral infarcts and cerebral white matter lesions in patients with nonvalvular atrial fibrillation
J Stroke Cerebrovasc Dis
(2012) - et al.
Cerebral microbleeds: a guide to detection and interpretation
Lancet Neurol
(2009) - et al.
Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study
Lancet Neurol
(2006) - et al.
Patients at high risk with atrial fibrillation: a prospective and serial follow-up during 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging
J Am Soc Echocardiogr
(2005) - et al.
Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients
J Am Coll Cardiol
(2013) - et al.
Cerebral microinfarcts: the invisible lesions
Lancet Neurol
(2012) - et al.
Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study
Stroke
(2002) - et al.
Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study
Stroke
(2008) Cardioembolic stroke: topography and pathogenesis
Cerebrovasc Brain Metab Rev
(1992)
Differential effect of aspirin versus warfarin on clinical stroke types in patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators
Neurology
Apixaban in patients with atrial fibrillation
N Engl J Med
Cited by (50)
Neuroimaging standards for research into small vessel disease—advances since 2013
2023, The Lancet NeurologyMechanisms and Clinical Manifestations of Cognitive Decline in Atrial Fibrillation Patients: Potential Implications for Preventing Dementia
2023, Canadian Journal of CardiologyCitation Excerpt :In the Rotterdam Study, patients treated with coumarin had a higher burden of CMB (OR, 1.70; 95% CI, 1.24-2.34) but no statistically significant greater risk for development of new CMB during follow-up (OR, 1.44; 95% CI, 0.89-2.32).78 In a randomized trial, there was no difference in the proportion of new CMB in patients who received apixaban compared with aspirin after a mean follow-up of 1 year (HR, 0.92; 95% CI, 0.53-1.60),79 and among patient with embolic strokes of undetermined source the HR of intracerebral hemorrhage of those who received rivaroxaban was similar in persons with and without CMB (P for interaction = 0.97).80 In a systematic review and meta-analysis of stroke patients there was an excess of CMB among those treated with warfarin in patients with hemorrhagic strokes, but not among those with ischemic strokes or transient ischemic attacks.81
Preceding direct oral anticoagulant administration reduces the severity of stroke in patients with atrial fibrillation – K-PLUS registry
2021, Journal of Clinical NeuroscienceAspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial
2021, The Lancet NeurologyCitation Excerpt :For this approach, the MRI substudy16 of the International Carotid Stenting Study served as a role model, because the comparative analysis of MRI outcomes in both treatment groups (ie, stenting versus carotid endarterectomy) resulted in nearly identical results to those in the main study based on purely clinical outcomes, with less than 10% of the patients from the main study. More recently, the MRI substudies of the AVERROES17 and the COMPASS18 randomised trials found that clinical and MRI outcomes were concordant and thus their combined use has been advocated. In line with this recommendation, the REDUCE trial19 implemented clinical and MRI outcomes as a co-primary outcome and showed the usefulness of this combination in a stroke-prevention randomised trial testing patent foramen ovale closure.
Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation
2019, Journal of the American College of CardiologyCitation Excerpt :Anticoagulation use was not associated with a higher microbleed count, and microbleed count was not associated with cognitive function. This finding is in agreement with data showing that aspirin and apixaban had a similar impact on the incidence of microbleeds (27). Currently available data therefore suggest that anticoagulation is safe in most patients with microbleeds, although it remains controversial whether there is a subgroup of patients with a high microbleed burden who should not be started on anticoagulation despite their high stroke risk (28,29).