Limitation
Our meta-analysis has several limitations. First, the thresholds for
defining polypharmacy status differed in each study, and subjects with
different baseline characteristics may have significant bias despite
statistical adjustments. Second, the included studies only assessed the
extent of patients’ polypharmacy at baseline and were unable to adjust
drug use for subsequent prescription changes. Fortunately, the burden of
co-morbidity in polypharmacy populations is often chronic, and the
number of drugs rarely changes significantly. In addition, the study did
not take into account non-prescription drugs and health products that
patients were taking, which could lead to a potential influence on the
results. Third, drug compliance largely determines how patients actually
take their medication. Unfortunately, the frequent dose changes of
warfarin prevented the study from further evaluating the compliance of
the two classes of oral anticoagulants. Finally, due to the limited
amount of data, we were unable to perform head-to-head comparisons among
NOACs, and more studies in the future may reveal which NOACs would be
more suitable for this population.