Introduction
Atrial
fibrillation (AF) is an age-related cardiac arrhythmia, and the elderly
aged between 65-85 have occupied nearly 70% of AF patients[1, 2].
Elderly AF patients are often accompanied by a huge comorbidity burden
and polypharmacy use. Polypharmacy refers to the situation in which an
individual uses multiple drugs at the same time, but there is no
international consensus on the threshold and measurement methods of drug
use[3].
In patients with AF, oral anticoagulation is necessary to prevent
thrombotic events. Current evidence has indicated that the non–vitamin
K antagonist oral anticoagulants (NOACs) served as a safer and more
effective alternative to warfarin for nonvalvular AF patients, featured
fewer drug-food interactions, and rapid onset of action[4-7].
However, when encountering polypharmacy, a critical treatment issue is
presented. In this setting, anticoagulated patients with polypharmacy
frequently exhibit an unexpected dose-response relationship to
oral anticoagulant (OAC) therapy,
in which polypharmacy has been demonstrated to be a risk factor for both
anticoagulation-related events such as bleeding and
thromboembolism[8-10].
Despite guideline recommendations [ESC, APHRS][11, 12], only
approximately 50% of elderly AF patients received OAC therapy[1].
On
the one hand, owing to the multiple comorbidities and polypharmacy,
these patients take the risks of pill burden, drug-drug interaction,
non-adherence, and adverse drug events[13]. On the other hand, the
bleeding risk associated with advanced age makes the use of
anticoagulants more cautious[14]. In this context, the exploration
of safe and effective OAC treatments for AF patients with polypharmacy
is necessary.
Several post-hoc analyses of randomized controlled trials (RCTs) in
patients with AF polypharmacy have been conducted. For example, Focks et
al. conducted a post-hoc analysis of the ARISTOTLE trial and showed that
apixaban was more effective than warfarin and was at least just as
safe[9]. Numerous real-world studies, such as the ARISTOPHANES study
have demonstrated that the effectiveness and safety profiles are more
favorable for NOACs vs warfarin[15].
We therefore performed this comprehensive systematic review and
meta-analysis via high-quality studies to determine the effectiveness
and safety of NOACs versus Vitamin K antagonists (VKAs) in AF patients
with polypharmacy. The aims of this meta-analysis were as follows: (1)
comparing the risks of stroke, death, and bleeding in AF patients with
and without polypharmacy; (2) assessing the efficacy and safety outcomes
of NOACs versus VKAs in patients with AF and polypharmacy; (3) assessing
the effects of NOACs versus VKAs in AF patients with and without
polypharmacy.