NOACs outperform warfarin in renal protection in Chinese patients with nonvalvular AF

A recent study led by researchers from the Chinese University of Hong Kong (CUHK) shows that non–vitamin K oral anticoagulants (NOACs) may be associated with a significantly lower risk of decline in renal function in Chinese patients with nonvalvular atrial fibrillation (NVAF) compared with warfarin.

“Our study’s findings showed that NOACs may be associated with a significantly reduced risk of long-term decline in renal function compared with warfarin in Chinese patients, suggesting that patients receiving oral anticoagulant therapy, particularly warfarin, should undergo close renal function monitoring during treatment,” said the authors. [Hong Kong Med J 2021;doi:10.12809/hkmj209201]

“The efficacy in stroke/systemic embolism [SE] prevention with NOACs vs warfarin was generally consistent with that previously reported, especially for dabigatran. Greater attention should be paid to the inconsistencies between NOAC  drug labelling and prescribing patterns in routine clinical practice, particularly with apixaban. Former studies had demonstrated that NOAC dose reduction in the absence of a renal indication was associated with reduced effectiveness and absence of safety benefit in apixaban-treated patients with normal or mildly impaired renal function,” they highlighted.

In the retrospective cohort study, data of 600 Chinese patients (median age, 75.8–77.8 years; CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, age 65–74 years, stroke/transient ischaemic attack/thromboembolism, vascular disease, diabetes mellitus, sex (female)] score, 4.1–4.2; estimated glomerular filtration rate [eGFR], 63.7–64.7 mL/min/1.73 m²) with NVAF receiving oral anticoagulant therapy (warfarin, n=200; rivaroxaban, n=200; dabigatran, n=100; apixaban, n=100) were retrieved from electronic medical records in the Prince of Wales Hospital of Hong Kong. The mean follow-up period was 1,000 days. 

Baseline characteristics between warfarin and each NOAC group were well balanced after weighting. The mean time in therapeutic range (TTR) of the warfarin cohort was 44.3 percent. A significantly lower frequency of dose reduction without a renal indication were found for dabigatran vs apixaban and rivaroxaban (2.0 percent vs 46.9 percent and 35.7 percent; p<0.001).

Results of pooled analysis showed a 66.1 percent risk reduction for ≥30 percent decline in eGFR (hazard ratio [HR], 0.339; 95 percent confidence interval [CI], 0.276 to 0.417; p<0.001) and a 45.0 percent risk reduction for doubling of serum creatinine (HR,0.550; 95 percent Cl, 0.387 to 0.782; p<0.001) with NOACs vs warfarin, particularly with dabigatran and rivaroxaban (≥30 percent decline in eGFR, both p<0.001; reduction of doubling of serum creatinine, both p<0.05)

A numerical reduction in risk of kidney failure was also seen with dabigatran and rivaroxaban vs warfarin (both p>0.05).

A significant risk reduction for all stroke (ischaemic or haemorrhagic)/SE vs warfarin was, however, found only with dabigatran (HR, 0.151; 95 percent Cl, 0.054 to 0.423; p<0.001).

Subgroup analysis showed consistent benefit in terms of risk reduction for ≥30 percent decline in eGFR with dabigatran and rivaroxaban vs warfarin across all subgroups. However, apixaban was not associated with a renal benefit in male patients (p=0.057), patients with heart failure (HF; p=0.835), and patients without diabetes mellitus (DM; p=0.090).

“Further studies are needed to improve the understanding of the impact on renal function with NOACs vs warfarin in Chinese populations. Head-to-head NOAC studies would allow direct comparison between individual NOACs to inform treatment selection. Further research is also required to enhance our understanding of the impact of pre-existing comorbidities [eg, DM, HF] on renal risk reduction in relation to the use of NOACs vs warfarin. Large-scale studies are also needed to investigate the impact of dosage patterns on renal outcomes,” said Lee.