Secondary outcomes
As shown in Supplementary Figure Ⅱ-Ⅵ , there was no significant difference in ischemic stroke (moderate polypharmacy: HR, 0.92 [95% CI, 0.80–1.08]; severe polypharmacy: HR, 0.90 [95% CI, 0.73–1.12]), all-cause death (moderate polypharmacy: HR, 1.02 [95% CI, 0.83–1.26]; severe polypharmacy: HR, 1.00 [95% CI, 0.75–1.33]), and gastrointestinal bleeding (moderate polypharmacy: HR, 1.09 [95% CI, 0.94–1.26]; severe polypharmacy: HR, 1.14 [95% CI, 0.94–1.39]) between the NOACs and VKAs users. The use of NOACs was associated with a reduced risk of any bleeding in AF patients with moderate polypharmacy (HR, 0.85 [95% CI, 0.72–1.00]) and severe polypharmacy (HR, 0.83 [95% CI, 0.72–0.95]). On the contrary, compared with VKAs, the risk of intracranial hemorrhage was reduced in patients with moderate polypharmacy (HR, 0.67 [95% CI, 0.46–0.98]) but not in patients with severe polypharmacy (HR, 0.68 [95% CI, 0.42–1.10]) in NOACs users.