NOACs in AF: Differences in Asians vs non-Asians

Pearl Toh
25 May 2018
Prof Gregory Lip

Non-vitamin K antagonist oral anticoagulants (NOACs) offer better efficacy and safety, especially in terms of risk of stroke and major bleeding, respectively than warfarin for Asian patients with atrial fibrillation (AF), according to a presentation at APSC Congress 2018. The benefits were also greater for Asians compared with non-Asians.     

“It’s pretty clear that the Asian participants [on NOACs] did far better in relative and in absolute terms compared with non-Asians,” said Professor Gregory Lip of Institute of Cardiovascular Sciences, University of Birmingham, UK. [APSC 2018, session S047-03]

Being highlighted was a meta-analysis of phase III clinical trials comparing the efficacy and safety of vitamin K antagonists (VKAs) and NOACs in Asian and non-Asian patients with AF. Compared with VKAs, the risk of stroke or systemic embolism was lower with standard-dose NOACs, with a significantly greater reduction seen in Asians compared with non-Asians (odds ratios [ORs], 0.65 vs 0.85; p-interaction=0.045). [Stroke 2015;46:2555-2561]

In terms of safety endpoints, reductions in the risk of major bleeding (ORs, 0.57 vs 0.89 for Asian vs non-Asian patients, respectively; p-interaction=0.004) and haemorrhagic stroke (ORs, 0.32 vs 0.56; p-interaction=0.046) with NOACs were also significantly greater in Asian than non-Asian patients.  

The findings persist in another study reviewing four phase III trials comparing NOACs vs warfarin in Asian patients. The absolute risk reductions with NOACs vs warfarin were consistently greater in Asians than non-Asians in terms of efficacy endpoints such as stroke/systemic embolization, haemorrhagic stroke, and all-cause death, and safety endpoints including major bleeding, intracranial haemorrhage, and all major/minor bleeds. [Int J Cardiol 2015;180:246-254]   

These data suggest that NOACs should be preferentially indicated for preventing stroke in Asians with AF, according to Lip.

Despite the better efficacy and safety with NOACs over warfarin, underdosing of NOACs remains a problem in AF management, both in Asian and non-Asian population, he pointed out.

In the ORBIT-AF registry study, 5,738 patients receiving a NOAC were classified as underdosed or overdosed, taking the recommended dose from the US FDA labelling as reference. Underdosing was associated with significantly higher rates of cardiovascular events compared with recommended doses (adjusted hazard ratio [HR], 1.26; p=0.007). Also, overdosing was associated with an increased risk of all-cause mortality vs dosing as recommended (HR, 1.91; p=0.04). [J Am Coll Cardiol 2016;68:2597-2604]

“There is this misconception that by prescribing a low dose, you are going to win on safety — [but] you don’t. [In reality,] that translates to worse outcomes,” cautioned Lip, noting that there is no reduction in major bleeds but more strokes in those who were underdosed.  

Similarities in guidelines

With regards to identifying AF patients requiring antithrombotic therapy, Lip said the Asian guidelines are largely similar to the Western guidelines.

“Guidelines now focus on initial identification of ‘low risk’ patients who do not need any antithrombotic therapy. Subsequent to this step, effective stroke prevention (ie, OAC) can be offered to patients with 1 stroke risk factor,” he explained. For example, the 2017 consensus paper by the Asia Pacific Heart Rhythm Society states that low-risk patients (defined by a CHAD2DS2-VASc=0 for male and =1 for female) identified using the HAS-BLED scoring system do not require antithrombotics. [J Arrhythm 2017;33:345-367] Also, NOACs featured prominently in patients with CHADS2 ≥1 in another Asian guideline. [Circ J 2014;78:1997-2021]

Nonetheless, Lip also drew attention to a recent finding that “stroke risk as assessed by the CHAD2DS2-VASc score is dynamic and changes over time in AF patients.” [Thromb Haemost 2018;doi:10.1055/s-0038-1651482]

“Rates of ischaemic stroke increased when patients accumulated risk factors, and were reclassified into higher CHAD2DS2-VASc score categories,” he continued.  

“In practical terms, that means stroke risk assessment is needed at every patient contact, as accumulation of risk factors with increasing CHAD2DS2-VASc score translates to greater stroke risks over time.”



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