Outcomes associated with apixaban vs warfarin in patients with renal dysfunction

Abstract

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

“…There remains a paucity of data evaluating anticoagulation therapy for treatment of acute VTE in the setting of advanced CKD stage IV or greater. In one retrospective cohort of patients with a creatinine clearance of less than 25 mL/min, similar rates of bleeding and thromboembolic events were observed when comparing apixaban to warfarin [ 29 ]. As apixaban has limited renal clearance at 27%, there remains interest in evaluating this treatment strategy for acute VTE in the setting of advanced CKD [ 13 ].…”

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

“…There have been several observational/real-world studies evaluating the efficacy and safety of DOACs in the setting of renal dysfunction (►Table 3). [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Observational studies are prone to bias, with studies that are small, have inconsistent or short follow-up, single-center, or have unmatched patients being more susceptible. Unfortunately, data specifically in patients with VTE are extremely limited, with most studies evaluating patients with NVAF.…”

“…Six retrospective observational studies included patients with VTE and NVAF. [43][44][45][46][47][48] In four of the studies, patients with VTE comprised approximately 20 to 25% of the population, while the other two studies had approximately 50% VTE patients. All of these studies compared apixaban to warfarin in patients with stage 4 or 5 CKD or dialysis.…”

“…44,46,48 In five of the six studies, less than half of the patients received full-dose apixaban. [44][45][46][47][48] Interestingly, in the two studies that evaluated the results based on dose, the rate of major bleeding was higher in patients receiving apixaban 2.5 mg twice daily compared with 5 mg twice daily. 45,47 The use of apixaban in NVAF patients on dialysis was also evaluated in a larger study using the U.S. Renal Data System, which collects data on all patients undergoing chronic dialysis.…”

“…[44][45][46][47][48] Interestingly, in the two studies that evaluated the results based on dose, the rate of major bleeding was higher in patients receiving apixaban 2.5 mg twice daily compared with 5 mg twice daily. 45,47 The use of apixaban in NVAF patients on dialysis was also evaluated in a larger study using the U.S. Renal Data System, which collects data on all patients undergoing chronic dialysis. 49 Similar to the results demonstrated in the single-center studies, patients receiving apixaban had similar efficacy compared with patients receiving warfarin, with a significant reduction in major bleeding (►Table 3).…”