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Asian AF patients with supranormal renal function fare better with NOACs vs warfarin

Jairia Dela Cruz
22 Jun 2019

Nonvitamin K antagonist oral anticoagulants (NOACs) perform better than warfarin for stroke prevention in Asian patients with nonvalvular atrial fibrillation (AF) and supranormal renal function, according to a study.

All four NOACs investigated in the study—rivaroxaban, dabigatran, apixaban and edoxaban—have shown similar trends toward lower risks of ischaemic stroke, intracranial haemorrhage (ICH), all-cause death, and their composite outcome in subgroups of patients with creatinine clearance (CrCl) >80 to 95 mL/min and >95 mL/min when compared with warfarin, the investigators said.

Using data from the Korean National Health Insurance Service database, the investigators looked at 24,974 patients, among whom 15,090 were treated with NOACs (rivaroxaban, n=6,297; dabigatran, n=4,241; apixaban, n=3,395; edoxaban, n=1,187) while 9,884 received warfarin for stroke prevention. The mean age of the entire cohort was 66 years, 63 percent of patients were men, and the mean CHA2DS2-VASc score was 3.0. The median follow-up duration was 1.2 years.

Cox regression analysis showed that compared with warfarin, pooled NOACs provided greater protection against the risks of ischaemic stroke (hazard ratio [HR], 0.51, 95 percent CI, 0.43–0.60), ICH (HR, 0.48, 0.37–0.63), major bleeding (HR, 0.67, 0.56–0.79), all-cause death (HR,0.71, 0.62–0.81) and the composite outcome (HR, 0.64, 0.58–0.70; p<0.01 for all). [Stroke 2019;50:1480-1489]

The superior protective benefits observed with NOACs were consistent in the subgroups of patients with CrCl >80 to 95 mL/min (n=13,745; HRs, 0.46 for ischaemic stroke, 0.58 for ICH, 0.68 for major bleeding, 0.65 for all-cause death, and 0.60 for the composite outcome; p<0.01 for all) and those with CrCl >95 mL/min (n=11,229; HRs, 0.56 for ischaemic stroke, 0.38 for ICH, 0.65 for major bleeding, 0.69 for all-cause death, and 0.79 for the composite outcome; p<0.01 for all except all-cause death [p=0.01]).

Furthermore, results for ischaemic stroke, ICH, all-cause death and the composite outcome tended to be more favourable with each NOAC vs warfarin in both CrCl >80 to 95 mL/min and >95 mL/min patient subgroups.

“The efficacy and safety of NOACs compared with warfarin for stroke prevention in patients with AF were consistently reported in pivotal randomized controlled trial,” the investigators noted. [N Engl J Med 2009;361:1139-1151; N Engl J Med 2011;365:981-992; N Engl J Med 2011;365:883-891; N Engl J Med 2013;369:2093-2104]

“Warfarin is metabolized by the liver. Thus, warfarin elimination is not governed by the kidney; in contrast, NOACs are eliminated via the kidney with different degrees of renal clearance,” they explained.

Despite the variability in renal elimination of different NOACs, apixaban was associated with the lowest risk for ischaemic stroke in both patients with CrCl >80 and >95 mL/min, having the lowest renal clearance proportion among the NOACs, as the investigators pointed out.

“Our findings are consistent with those of previous reports; furthermore, we provide novel evidence on the effectiveness and safety of apixaban for patients with CrCl >95 mL/min in the actual clinical setting,” the investigators said.

“Further investigation is required to evaluate the differential effect of NOAC compared with warfarin among various ranges of CrCl in the Asian population,” they added.

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