Renal function status had no effect on the superiority of apixaban in efficacy and safety compared with warfarin in patients with atrial fibrillation, according to data published in JAMA Cardiology.
In the ARISTOTLE trial, apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was associated with reduced risk for stroke, mortality and major bleeding compared with warfarin. The current analysis investigated whether the safety and efficacy of apixaban was affected by worsening renal function.
Patients with AF (n = 18,201) were randomly assigned warfarin (n = 9,081) or apixaban (n = 9,120). The primary efficacy endpoint was stroke or systemic embolism, and the primary safety endpoint was major bleeding.
Ziad Hijazi, MD, PhD, from the department of medical sciences, cardiology at Uppsala University in Sweden, and colleagues analyzed whether the results varied by renal function.
The median estimated glomerular filtration rate (eGFR) decline was 1.02 mL/min (25th-75th percentile, –6.72 mL/min to 4.52 mL/min). At 12-month follow-up, 4,374 patients had good renal function (eGFR > 80 mL/min). However, if a higher cutoff (eGFR > 95 mL/min) was used, then only 1,038 patients had good renal function. Worsening of eGFR by at least 20% occurred in 2,294 patients (13.6%).
Outcomes by renal function
In patients with stable renal function, the annual stroke rate was 0.9% in patients with eGFR at least 80 mL/min at randomization (n = 97), 1.31% in patients with eGFR 50 mL/min to 80 mL/min (n = 126), and 2.03% in patients with eGFR up to 50 mL/min (n = 70). In addition, all-cause mortality was three times higher in patients with stable eGFR up to 50 mL/min compared with patients with stable eGFR greater than 80 mL/min (6.64% vs. 2.14%). A similar pattern was observed with incidence of major bleeding (3.81% vs. 1.34%).
Although the risk for stroke/systemic embolism (HR = 1.53; 95% CI, 1.17-2.01), major bleeding (HR = 1.56; 95% CI, 1.27-1.93) or mortality (HR = 2.31; 95% CI, 1.98-2.68) remained higher in patients with a worsening eGFR of at least 20%, the RRs for stroke or major bleeding with apixaban remained lower than the risks with warfarin. In this population, compared with warfarin, apixaban had an HR of 0.8 (95% CI, 0.51-1.24) for stroke or systemic embolism, an HR of 0.88 (95% CI, 0.52-1.48) for ischemic or unspecified stroke and an HR of 0.76 (95% CI, 0.54-1.07) for major bleeding, according to the researchers.
The benefit of apixaban over warfarin for prevention of stroke or systemic embolism and major bleeding also was consistent regardless of level of renal function over time, Hijazi and colleagues wrote.
“The results from this study verified a mean slow gradual reduction of renal function over time in patients with AF treated with oral anticoagulants,” Hijazi and colleagues wrote.
However, when compared with warfarin, apixaban “was associated with lower risk of stroke, death and major bleeding in patients, regardless of baseline and changes of renal function.” – by Tracey Romero
ARISTOTLE was funded by Bristol-Myers Squibb and Pfizer. Hijazi reports receiving lecture fees from Boehringer Ingelheim, consultant fees from Bristol-Myers Squibb and Pfizer, and institutional research grants from Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.