Yan Hou, MD, PhD
Paciaroni
M, Agnelli G, Caso V, Silvestrelli G, Seiffge DJ, Engelter S, et al. Causes and
Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation
Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention:
The RENo Study. Stroke. 2019;50:2168–2174
Non–vitamin K antagonist
oral anticoagulants (NOACs) are currently recommended as the stroke prevention
for patients with nonvalvular atrial fibrillation (AF). Despite compliance with
NOAC, patients with nonvalvular AF may still experience ischemic
cerebrovascular events. The RENO study is a multicenter case-control study to
identify the etiology and risk factors for ischemic events occurring during
NOACs (dabigatran, apixaban, rivaroxaban, or edoxaban) therapy in patients with nonvalvular
AF.
The study included 713
cases (641 ischemic strokes and 72 TIA) and 700 controls (patients did not
experience cerebrovascular events). Cases who did not guarantee compliance or who had suspended
NOAC at least 24 hours before the cerebrovascular event were excluded. Most
strokes (64%) occurring during NOACs therapy were caused by cardioembolism, but
about 30% of strokes were found due to non-cardioembolic etiology. Among the
risk factors (age, sex, hypertension, diabetes mellitus, current cigarette
smoking, hyperlipidemia, ischemic heart disease, peripheral artery disease,
alcohol abuse, obesity, previous stroke/transient ischemic attack, creatinine
clearance, duration of NOAC treatment, doses of NOACs, AF classification, CHA2DS2-VASc score, left atrial
enlargement on echo), off-label low doses of NOACs (OR, 3.18), atrial
enlargement (OR, 6.64), hyperlipidemia (OR, 2.40), and high CHA2DS2-VASc score (OR, 1.72 for
each point increase) were associated with ischemic events. The reasons for
prescribing low doses of NOAC included fear of bleeding, history of bleeding,
concomitant antiplatelet therapy, recurrent falls, amyloid angiopathy, anemia,
history of cancer, age, gastrointestinal discomfort, and hypertension or other
causes. Low clearance of creatinine (OR, 0.98 for 1 mL/min increase) and high
CHA2DS2-VASc score (OR, 1.35 for
each point increase) were also found associated with prescription of low-dose
NOACs.