COMPARATIVE OUTCOMES OF APIXABAN VERSUS WARFARIN INITIATION IN PATIENTS ON HEMODIALYSIS WITH NEWLY DIAGNOSED ATRIAL FIBRILLATION

An increasing number of patients with kidney failure on hemodialysis (HD), who are newly diagnosed with atrial fibrillation (AF), initiate oral anticoagulation, mostly using warfarin or apixaban. We sought to compare the outcomes of patients initiating the vitamin K antagonist, warfarin, to those initiating the factor Xa inhibitor, apixaban.

Using the US Renal Data System (2014-19), we conducted a retrospective, propensity-matched cohort study of Medicare-insured patients on HD with newly diagnosed AF who were previously OAC naïve and initiated warfarin or apixaban within 30 days of their first AF diagnosis. We ascertained an array of sociodemographic, comorbidities, and laboratory markers to fit a rich logistic regression model to calculate each person’s expected propensity to initiate apixaban versus warfarin. After propensity-matching each warfarin user to an apixaban user, we followed patients for up to one year for the incidence of thromboembolic events (ischemic stroke, myocardial infarction, or a composite endpoint additionally including pulmonary embolism, deep venous thrombosis, and cardiovascular death), bleeding events (hemorrhagic stroke, clinically significant bleeding), any stroke (ischemic or hemorrhagic), and all-cause mortality. In order to examine the potential for residual confounding from unobserved selection bias, we studied two ‘control’ outcomes which we hypothesized should not plausibly differ between the treatments: pneumonia and hip fracture. All outcomes were ascertained from principal diagnosis codes in inpatient medical claims. We used Cox proportional hazards models (with competing risk approach, where indicated) to estimate hazard ratios (HR) and 95% confidence intervals (CI) using both an intent-to-treat and an as-treated framework. The latter censored patients after their supplied medication ran out without any new prescription being filled.

Of 75,269 HD patients newly diagnosed with AF, 6,967 initiated warfarin and 4,283 apixaban. After excluding patients with missing clinical information, we matched 3,978 warfarin users to 3,978 apixaban users. All baseline characteristics were well balanced between the groups. Compared with warfarin users, apixaban users had lower rates of ischemic stroke (HR=0.65; 95% CI, 0.51-0.84), whereas there were no differences in myocardial infarction (HR=0.95; 95% CI, 0.80-1.11) or the composite endpoint (HR=0.99; 95% CI, 0.91-1.08). The rate of hemorrhagic stroke did not differ between the groups (HR=0.88; 95% CI, 0.62-1.25), but the rate of clinically important bleeding was lower in the apixaban group (HR=0.70; 95% CI, 0.63-0.78). There was a lower rate of any stroke in apixaban users (HR=0.74; 95% CI, 0.60-0.91). All-cause mortality did not differ between groups (HR=0.96; 95% CI, 0.88-1.05). Results from as-treated analyses were qualitatively similar, albeit with lower rates of myocardial infarction in apixaban users (HR=0.69; 95% CI, 0.52-0.93). The rates of the control outcomes, pneumonia and hip fracture, did not differ between groups.

Patients initiating apixaban within 30 days from a new AF diagnosis had reduced rates of ischemic stroke and less bleeding compared with otherwise similar patients who initiated warfarin. This study supports choosing apixaban over warfarin to orally anticoagulate patients on HD who are newly diagnosed with AF.