Role of Biological Markers for Cerebral Bleeding Risk STRATification in Patients with Atrial Fibrillation on Oral Anticoagulants for Primary or Secondary Prevention of Ischemic Stroke (Strat-AF Study): Study Design and Methodology

Abstract

Background and Objectives: In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. Cerebral small vessel disease (SVD) represents the pathologic substrate for primary intracerebral hemorrhage and ischemic stroke. We hypothesize that biological markers—both circulating and imaging-based—and their possible interaction, might improve the prediction of bleeding risk in AF patients under treatment with any type of oral anticoagulant. Materials and Methods: The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with AF, aged 65 years or older, and with no contraindications to magnetic resonance imaging (MRI), referring to Center of Thrombosis outpatient clinic of our University Hospital for the management of oral anticoagulation therapy. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral MRI, and circulating biomarkers assessment at baseline and after 18 months. The main outcome is SVD progression—particularly microbleeds—as a selective surrogate marker of hemorrhagic complication. Stroke occurrence (ischemic or hemorrhagic) and the progression of functional, cognitive, and motor status will be evaluated as secondary outcomes. Circulating biomarkers may further improve predictive potentials. Results: Starting from September 2017, 194 patients (mean age 78.1 ± 6.7, range 65–97; 61% males) were enrolled. The type of AF was paroxysmal in 93 patients (48%), and persistent or permanent in the remaining patients. Concerning the type of oral anticoagulant, 57 patients (29%) were on vitamin K antagonists, and 137 (71%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI are ongoing. Conclusions: The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in AF, and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.

Can CHA2DS2-VASc and HAS–BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat–AF Study

“…Stratification of cerebral bleeding risk in AF, http://www.strataf.it (Strat-AF) is an observational, prospective, single-center hospital-based study enrolling elderly patients with AF, referred from the outpatient clinic Center of Thrombosis of Careggi University Hospital in Florence where they are followed for the management of oral anticoagulation therapy in primary or secondary prevention of thromboembolic events. Strat-AF study design and methodology have been previously described (16). In brief, the main aim of Strat-AF study is to evaluate the added value of circulating and brain MRI biomarkers on the prediction of cerebral bleeding risk.…”

“…The MRI protocol included the following sequences: Sagittal T1-weighted spinecho, coronal T2-weighted Turbo spin-echo; axial fluidattenuated inversion recovery (FLAIR); axial gradient-echo T2 * (FFE); axial diffusion weighted imaging (DWI); sagittal magnetization prepared rapid acquisition gradient-echo 3D T1weighted (T1 TFE 3D) followed by MultiPlanar reconstruction (MPR) in axial, coronal, and sagittal planes. Further details are reported in the methodology study (16).…”

Association Between Motor and Cognitive Performances in Elderly With Atrial Fibrillation: Strat-AF Study

“…Clinico-radiological follow-up is still in progress. Study design and methodology have been previously described (21). At enrollment, data on demographic characteristics (age, sex, years of education), previous stroke events, and vascular risk factors and comorbidities (hypertension, diabetes, dyslipidemia, physical activity, smoking habits, alcohol consumption, peripheral arterial disease, ischemic heart disease, myocardial infarction, heart failure) were collected.…”

“…The neuropsychological battery included the Montreal cognitive assessment test (MoCA) as a global cognitive functioning test and 6-s level tests for the evaluation of the following domains: verbal memory (Rey Auditory-Verbal Learning Test, short-story test), attention and executive functions (visual search test, Color Word Stroop), and language (semantic verbal fluency test, sentence construction test) (21). Neuropsychological tests' raw scores were corrected for demographics according to the Italian population normative data, and then used in the statistical analyses as continuous variables.…”

Stroke, Dementia, and Atrial Fibrillation: From Pathophysiologic Association to Pharmacological Implications

“…Poggesi et al present the design, methodology, and preliminary results of the Strat-AF study [20]. This prospective observational study is primarily aimed at investigating how circulating biomarkers might help to further stratify the cerebral bleeding risk of AF patients on oral anticoagulation therapy.…”