350Six-month treatment with novel oral anticoagulants ameliorates cerebral blood flow, as evaluated with brain perfusion SPECT

Abstract

Background: Dementia is a serious clinical problem. Cerebral blood flow is decreased even in patients with mild cognitive impairment, and the dysregulation of cerebral blood flow contributes to the pathogenesis of Alzheimer disease. Decreases in regional cerebral blood flow have been reported, as detected by brain perfusion positron-emission single-photon emission tomography (SPECT). Novel oral anticoagulants (NOACs) are used to treat patients with non-rheumatic atrial fibrillation (AF). However, the effects of NOACs on cerebral blood flow remain unknown. Purpose: The purpose of this study was to determine whether six-month treatment with NOACs in patients with cardiovascular diseases such as hypertension, dyslipidemia, and angina pectoris ameliorates cerebral blood flow using brain perfusion SPECT. Methods: We performed technetium-99m ethyl cysteinate dimer SPECT on 50 consecutive Japanese patients (30 men and 20 women, aged 74.9±9.9 years) with hypertension (31), dyslipidemia (8), angina pectoris (8), diabetes mellitus (6), or AF (5), but without thoracic surgery or catheter ablation, before and after six-month treatment with NOACs. Results: The results of brain perfusion SPECT before and after six months of treatment with NOACs were respectively 1.26±0.36 and 1.17±0.43 for severity (p<0.01), 13.3±11.9% and 12.0±12.9% for extent (p<0.05), and 1.44±1.06 and 1.24±1.05 for the ratio (p=0.097). Significant differences (p<0.05) were obtained in the patients before and after six-month treatment with NOACs, as assessed based on severity and extent according to the eZIS system. Improvement of cerebral blood flow, which was assessed based on severity, was found in 36 (72%) patients (22 men and 14 women, aged 75.4±9.5 years). Among the patients with improved cerebral blood flow, 18 (50%) patients were treated with edoxaban; 8 (22%), with apixaban; 6 (16%), with rivaroxaban; and 4 (11%), with dabigatran. Among 22 patients treated with edoxaban, cerebral blood flow was increased in 18 (82%) patients, and among 11 patients treated with rivaroxaban, cerebral blood flow was increased in 6 (55%) patients. There was no statistically significant difference between edoxaban and rivaroxaban. Among 5 AF patients, 4 (80%) patients had improved cerebral blood flow. Additionally, the results of brain perfusion SPECT before and after six-months of treatment with edoxaban were 1.18±0.26 and 1.02±0.34 for severity (p<0.01), 10.1±6.2% and 6.7±6.6% for extent (p<0.01), and 3.72±6.96 and 0.88±0.74 for ratio (p=0.052), respectively. NOACs can possibly prevent dementia by increasing cerebral blood flow. Conclusion: Six-month treatment with NOACs improved cerebral blood flow in patients with cardiovascular diseases such as hypertension, dyslipidemia, angina pectoris, diabetes mellitus, and AF, as evaluated with brain perfusion SPECT.