Apixaban Cuts Recurrent Venous Thromboembolism Risk in CKD Better Than Warfarin

Risk of recurrent venous thromboembolism (VTE) in patients with chronic kidney disease (CKD) and VTE was significantly reduced in those who were treated with apixaban vs warfarin, investigators concluded.

Apixaban (Eliquis) was found to be associated with a significantly lower risk of recurrent venous thromboembolism (VTE) and major bleeding compared with warfarin (Jantoven; Coumadin) among patients with chronic kidney disease (CKD) and VTE, according to a recent study.

The retrospective cohort analysis, published in Thrombosis and Haemostasis, compared the effectiveness and safety outcomes of apixaban vs warfarin among patients with VTE and CKD, including those with end-stage renal disease (ESRD), a subgroup of the CKD population that has largely been left out of studies regarding the effects of direct oral anticoagulants (DOACs) on VTE.

Data has shown that patients with CKD are at a greater risk of developing VTE. Additionally, decreased renal function increased risk of bleeding, particularly those in advanced disease stages, suggesting that treatment with anticoagulants in VTE patients with CKD must create a balance between preventing thrombosis and limiting hemorrhage.

Although there are real world studies evaluating the effects of DOACs among patients with VTE and CKD, they are often limited to a single center or a single data provider. The investigators of the present analysis utilized data from the CMS fee-for-service Medicare database and 4 US commercial claims databases to evaluate real world data.

For inclusion, patients with CKD has to have at least 1 medical claim for VTE in any position in the inpatient or outpatient setting between September 1, 2014 and the end of the study period depending on the database (MarketScan: September 2018; Optum and Humana: December 2018; PharMetrics: March 2019; CMS Medicare: December 2016). The patients had to be aged 18 years or older for the commercial databases and aged 65 or older for the Medicare database. They also had to have at least 1 pharmacy claim for apixaban or warfarin during the first 30 days following the index VTE event. The patients were stratified by CKD stage: stage 1 or 2, stage 3, stage 4, stage 5 or ESRD, or unspecified.

The investigators identified 29,790 patients with CKD and VTE, of whom 10,669 (35.8%) were treated with apixaban and 19,121 (64.2%) were treated with warfarin. The average (SD) age of the cohort was 75.1 (12.2) years and 75.2 (12.2) years for the apixaban and warfarin groups, respectively and 43.2% and 45.0% of the patients were male, respectively.

Among the patients, 49.4% has CKD stage 3, 17.6% had an unspecified CKD stage, 12.8% had stage 4, 12.0% had stage 5 or ESRD, and 8.2% had stage 1 or 2 CKD.

The patients treated with apixaban were found to have a significantly lower risk of recurrent VTE (HR, 0.78; 95% CI, 0.66-0.92), major bleeding (HR, 0.76; 0.65-0.88), and clinically relevant nonmajor bleeding (CRNMB; HR, 0.86; 95% CI, 0.80-0.93) compared with those treated with warfarin.

During the follow-up period, the patients with stage 5 or ESRD had the highest incidence rate of recurrent VTE, major bleeding, and CRNMB. Across all CKD stages, the patients treated with apixaban had a lower incidence of recurrent VTE compared with the patients treated with warfarin (stage 5/ESRD, 7.7 vs 11.6; stage 4, 5.8 vs 7.8; stage 3, 6.2 vs 6.9; stage 1/2, 5.2 vs 7.6). A similar trend was also seen between the patients treated with apixaban vs warfarin regarding major bleeding (stage 5/ESRD, 16.9 vs 18.0; stage 4, 12.6 vs 12.8; stage 3, 7.3 vs 9.6; and stage 1/2, 2.9 vs 6.6).

The study had several limitations, including that causal relationships can’t be inferred from the results, CKD was determined without any laboratory data for renal function, patients with stage 1 or 2 CKD may be underreported, and that the patient population did not include uninsured patients, limiting the generalizability of the results.

“While this study provides additional evidence to support the use of apixaban by VTE patients with CKD, more studies are needed to confirm our findings,” wrote the investigators.


Cohen AT, Sah J, Dhamane AD, et al. Effectiveness and safety of apixaban versus warfarin in venous thromboembolism patients with chronic kidney disease. Tromb Haemost. Published online December 28, 2021. doi: 10.1055/s-0041-1740254.