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

Recent Trials

The landmark trials assessing the efficacy and safety NOAC have led to a paradigm shift of the management of atrial fibrillation and VTE from VKAs to NOACs. The American Heart Association (AHA) and the Canadian Cardiovascular Society recognize NOACs as preferable or equivalent therapies to warfarin for the management of nonvalvular atrial fibrillation.[46,47] The American College of Chest Physicians (CHEST) identifies NOACs as preferable long-term anticoagulants in noncancer-related DVT and pulmonary embolism.[48] Recent studies have re-analysed data from these landmark trials focusing on reduced eGFRs and its effects on the efficacy and safety of NOACs.[34,49,50]

A recent study[34] conducted a post hoc analysis of The Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation (ROCKET-AF)[27] trial (Table 2). The investigators reanalyzed the patients with at least four creatinine measurements at set intervals. Worsening renal function was defined as a deterioration of more than 20% of CrCl from screening measurement at any time during the study period. Participants with worsening renal function on rivaroxaban had a reduction in stroke or systemic embolism compared with worsening renal function on warfarin (hazard ratio 0.50, 95% CI 0.27–0.93; P = 0.05). This was not observed in the stable renal function population. No significant difference between participants with worsening renal function on rivaroxaban or warfarin in regard to safety was appreciated.

A similar study[49] re-analysed the data of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial[25] (Table 2). The investigators[49] divided participants into three groups based on renal function (eGFR >80 ml/min, eGFR 50–80 ml/min, eGFR <49 ml/min) and a fourth group for patients with worsening renal function (eGFR deterioration >20%). Patients randomized to apixaban had improved outcomes independent of renal function. Worsening renal function was associated with overall worse outcomes irrespective of baseline renal function. However, the relative risk of stroke or systemic embolism (hazard ratio 0.80, 95% CI 0.51–1.24; P = 0.86), ischemic or unspecified stroke (hazard ratio 0.88, 95% CI 0.52–1.48, P = 0.94) and major bleeding (hazard ratio 0.76, 95% CI 0.54–1.07, P = 0.73) was lower in participants randomized to apixaban compared with warfarin.

The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis in Myocardial Infarction Study 48) trial[41] assessed the efficacy and safety of edoxaban against warfarin (Table 2). Investigators[50] conducted a subgroup analysis based on high-dose edoxaban (HDER) or low-dose edoxaban (LDER) regimens versus dose-adjusted warfarin [target international normalized ratio (INR) 2.0–3.0] and kidney function (CrCl 30–50 ml/min; CrCl 51–95 ml/min; CrCl >95 ml/min). The primary efficacy outcomes, for both HDER and LDER compared with warfarin for CrCl 30–50 ml/min and CrCl 50–95 ml/min were not statistically significant. Major bleeding was significantly reduced for both HDER and LDER whenever compared with warfarin for both the reduced renal function groups. Further, HDER and LDER versus warfarin was statistically significant in reducing composite outcomes of stroke, systemic embolism, major bleeding, or death at CrCl 30–50 ml/min and CrCl 51–95 ml/min.

These post hoc analyses continue to demonstrate the efficacy and safety of NOACs in patients with CKD or worsening kidney function. However, the relatively small numbers of the subgroup analyses and focus on only one NOAC per study makes inferences about which NOAC is preferable in CKD a difficult task.