Novel Oral Anticoagulants in Chronic Kidney Disease: Ready for Prime Time?

Justin Ashley; Manish M. Sood


Curr Opin Nephrol Hypertens. 2018;27(3):201-208. 

In This Article

Results From Recent Network Meta-analyses

A recent meta-analysis assessed the efficacy of NOACs against warfarin in regards to efficacy in CKD[51] (Table 3). Investigators found[51] a 21% reduction in the odds of stroke or systemic VTE for high-dose NOACs compared with warfarin (0.79, 95% CI 0.67–0.94). A 29% reduction was found between high-dose NOACs and low-dose groups (0.71, 95% CI 0.57–0.89). The investigators then conducted a network analysis to assess the[51] comparative effectiveness of dose anticoagulants in patients with atrial fibrillation and CKD (CrCl 25–30 ≤50 ml/min; Table 3). Only dabigatran 150 mg was statistically superior to warfarin in reducing the efficacy outcome (OR 0.56, 95% CI 0.36–0.86). Other NOACs were comparable with VKA for stroke and VTE reduction.

Three recent meta-analyses assessed NOACs relative safety against warfarin. Two meta-analyses demonstrated NOACs to have a superior safety profile than warfarin in the CKD population[33,51] (Table 3). One study[51] found the incidence of major bleeding was lower with NOACs than with warfarin in a dose-dependent fashion (OR 0.61, 95% CI 0.50–0.74 for low-dose NOACs and OR 0.74, 95% CI 0.65–0.86 for full/single-dose NOACs, both as compared with warfarin). Other investigators[33] (Table 3) found that the composite risk of major bleeding was reduced by 19% in patients with reduced eGFRs taking NOACs compared with VKAs (RR 0.81; 95% CI 0.71–0.93). This effect held for patients with mild (RR 0.81, 95% CI 0.73–0.90) and moderate kidney disease (RR 0.82, 95% CI 0.72–0.94).

One study[52] (Table 3) did not demonstrate a statistically significant difference between patients on NOACs against VKAs in both minor kidney disease (CrCl 50–80 ml/min; RR 0.87 [95% CI 0.81–0.93]) and moderate kidney disease (CrCl <25–49 ml/min; RR 0.83 [95% CI 0.68–1.02]) in regards to safety. However, whenever individual NOACs were analysed in subgroup analysis, apixaban and edoxaban were associated with a decreased risk for major bleeding in patients with a CrCl less than 50 ml/min (apixaban – RR 0.52; CI 0.40–0.68; edoxaban – RR 0.77; CI 0.40–0.68).[52] Whenever the atrial fibrillation population was analysed separately, NOACs were associated with lower risk of major bleeding as compared with VKAs for CrCl 50–80 ml/min (RR 0.89, 95% CI 0.81–0.97). In VTE sub-group, patients on NOACs experienced a significantly lower risk of major bleeding for CrCl 50–80 ml/min (RR 0.84, 95% CI 0.74–0.94).

Two studies conducted subsequent network analyses to determine a safety profile between NOACs.[51,52] The first study found[51] NOACs were associated with lower incidence of major bleeding in a dose-dependent fashion. However, only apixaban and high-dose edoxaban were associated with less major bleeding amongst high-dose regimens (apixaban – OR 0.49, 95% CI 0.37–0.66; edoxaban high dose – OR 0.72, 95% CI 0.55–0.96) compared with warfarin. Amongst full-dose NOACs, only apixaban and high-dose edoxaban reduced major bleeding (versus dabigatran 150 mg: OR 0.49, 95% CI 0.33–0.72; versus rivaroxaban: OR 0.60, 95% CI 0.38–0.93).

Similar results were seen in another recent meta-analysis by[52] (Table 3). Investigators found that in patients in whom atrial fibrillation or VTE and a CrCl less than 50 ml/min, apixaban as the only NOAC superior to VKA in terms of reducing bleeding (OR 0.49; 95% CI 0.37–0.65). However, low-dose edoxaban regimens were not included in the analysis.

Cumulatively, these studies continue to affirm that NOACs, as a class of drugs, offer either an equivalent[11,52] or superior safety[33,51] and efficacy profile than VKAs in patients with impaired kidney function. Further, network meta-analyses support NOACs as equivalent or superior to VKAs in preventing stroke and systemic embolism.[51] In particular, dabigatran 150 mg daily and apixaban seem to be the most efficacious in patients with atrial fibrillation and a CrCl of 25–30 to 50 ml/min and apixaban has been identified as a particularly well tolerated medication in the CKD population for both atrial fibrillation and VTE.