Initiation of Apixaban Versus Warfarin in Patients With Kidney Failure on Hemodialysis With Newly Diagnosed Atrial Fibrillation: A Target Trial Emulation.

RATIONALE &

OBJECTIVE

Patients with kidney failure on hemodialysis (KFHD) and atrial fibrillation (AF) are at high risk of ischemic stroke. Oral anticoagulation (OAC) may reduce this risk but at the expense of excess bleeding. We emulated a randomized comparative effectiveness trial of apixaban versus warfarin initiation in patients with KFHD and newly diagnosed AF.

STUDY

DESIGN

Trial emulation embedded in the US Renal Data System.

SETTING &

PARTICIPANTS

Medicare-insured patients with KFHD and newly diagnosed AF without recent OAC use (2014-2019).

EXPOSURES: Initiation of apixaban versus warfarin within 30 days from AF diagnosis.

OUTCOMES: Ischemic stroke, clinically important bleeding (co-primary outcomes). Other thromboembolic and bleeding events, death (secondary).

ANALYTICAL APPROACH: We compared propensity-matched new users of apixaban and warfarin using Cox proportional hazards models.

RESULTS

Among previously OAC-naïve patients with KFHD and newly diagnosed with AF, 3985 initiated apixaban and 6426 initiated warfarin. Propensity matching 3978 apixaban users with 3978 warfarin users balanced all measured characteristics. Median CHA2DS2-VASc score was 4 (IQR: 3-5). Apixaban was initiated a median 6 (IQR: 3-12) days after AF and used for a median 58 (IQR:37-135) days; warfarin was initiated a median 5 (IQR: 2-12) days after AF and used for a median 93 (IQR:38-238) days. In intention-to-treat analyses, rates of ischemic stroke were 34% lower (HRITT=0.66; 95%CI, 0.47-0.94; p=0.02) and rates of clinically important bleeding were 28% lower (HRITT=0.72; 95%CI, 0.63-0.83; p<0.001) in patients who initiated apixaban. All-cause mortality did not differ between groups; neither did negative control outcomes of hip fracture and pneumonia. Results were robust when restricting analyses to patients with CHA2DS2-VASc score of ≥2.

LIMITATIONS: Potential for residual confounding.

CONCLUSIONS

Initiating apixaban soon after newly diagnosed AF was associated with lower risks of ischemic stroke and clinically important bleeding compared with initiating warfarin.