When making practical decision on using non-vitamin K antagonist oral anticoagulants (NOACs), several factors should be considered such as age, renal function, and risk of bleeding, according to a presentation at the APSC Congress 2018.

The Asia Pacific Heart Rhythm Society (APHRS) 2017 consensus paper states that “for Asian patients with nonvalvular atrial fibrillation (AF), standard-dose NOACs are the default doses of choice for stroke prevention unless label guidance recommends low-dose regimens.” [J Arrhythm 2017;33:345-367]

“Aspirin is not recommended solely for stroke prevention in AF,” said Dr Chan Yi-Hsin of Chang Gung Memorial Hospital, Linkou, Taiwan.

The recommendations from APHRS are generally aligned with the ACC* and ESC** guidelines, he noted, which indicate that low-risk patients (defined by a CHAD₂DS₂-VASc=0 for male and =1 for female) do not require antithrombotics. On the other hand, higher-risk patients (CHAD₂DS₂-VASc ≥2 for all or =1 for male) were recommended to be further assessed with the SAMeTT₂R₂ score to guide the choice of anticoagulants — NOACs are preferred if the final score is ≥3. [J Arrhythm 2017;33:345-367]

How and what to select?

In selecting which NOAC to use, clinicians need to consider the CHAD₂DS₂-VASc score, age, renal and liver function, risk of bleeding, and concurrent medications a patient is receiving, Chan pointed out. [APSC 2018, session S047-04]

If CHAD₂DS₂-VASc=0/1, dabigatran or apixaban can be considered, based on findings from the RELY and ARISTOTLE trials which involved 30–34 percent of lower-risk patients in the overall study population. [N Engl J Med 2009;361:1139-1151; N Engl J Med 2010;363:1875-1876; N Engl J Med 2011;365:981-992] In higher-risk patients, the ENGAGE AF-TIMI 48 trial involving 77.4 percent of patients with CHAD₂DS₂-VASc=2 suggests the use of edoxaban in such patients, while the ROCKET AF study comprising 87 percent of patients with CHAD₂DS₂-VASc ≥3 indicates that rivaroxaban be used in these patients. [N Engl J Med 2011;365:883-891; N Engl J Med 2013;369:2093-2104]

Nonetheless, Chan was quick to point out that there are no head-to-head trials comparing the different NOACs so far, and the above suggestions are based on review of the various randomized controlled trials comparing each NOAC with warfarin.

When selecting NOAC in elderly patients (aged ≥75 years), a review study on phase III randomized clinical trials (RCTs) suggests that the risk of bleeding was reduced with apixaban 5 mg BID vs warfarin but the converse was seen (ie, warfarin was favoured) when compared with rivaroxaban 20 mg QD or dabigatran 110/150 mg BID in elderly patients. [Best Pract Res Clin Haematol 2013;26:215-224]

As different NOAC has different renal excretion rate, AF patients with impaired renal function (eGFR*** <50 mL) can consider dabigatran up to 150 mg with regards to efficacy (in terms of reduction in stroke rates), said Chan. [N Engl J Med 2009;361:1139-1151] However, in terms of safety outcome, apixaban can be considered in these patients as previous finding has shown a greater extent of reduction in major bleeding risk with apixaban vs warfarin. [N Engl J Med 2011;365:981-992]

“NOACs can [also] be used in patients with mild or moderate liver impairment (Child-Pugh categories A and B), with no dose reduction required for any of the NOAC in AF patients with Child-Pugh category A impairment,” said Chan. “NOACs are not recommended for those in Child-Pugh category C.” [Eur Heart J 2018;39:1330-1393]

One should also consider drug-drug interactions of NOACs with other medications a patient is taking, advised Chan. For example, in AF patients who are also taking HIV protease inhibitor or anti-epileptic drugs (such as carbamazepine, phenobarbital, phenytoin), all NOACs are contraindicated. [J Formos Med Assoc 2016;115:893-952; J Arrhythm 2017;33:345-367]

When to stop and restart?

“Renal function and surgical factors [ie, bleeding risk for surgery] help to determine when to discontinue and restart a NOAC for elective surgery,” said Chan.

According to the APHRS, TSOC, and THRS^# guidelines, AF patients with normal renal function can stop any of the NOAC ≥24 hours before an elective surgical intervention classified to be of low bleeding risk and ≥48 hours for high bleeding risk. However, in AF patients with renal impairment, a longer duration of NOAC discontinuation before an elective surgery needs to be considered for those on dabigatran. [J Formos Med Assoc 2016;115:893-952; J Arrhythm 2017;33:345-367]

“Heparin/LMWH^## bridging is generally not necessary for NOACs. NOAC is uninterrupted when performing AF catheter ablation,” said Chan.

“Generally, NOACs can be restarted 24 hours post-procedure with low-bleeding risk, and 48–72 hours post-procedure with high-bleeding risk. For procedure in which immediate and complete haemostasis can be achieved (eg, pacemaker implantations and skin surgery), NOACs can be resumed 6–8 hours after the interventions,” he added, citing recommendations from the ESC, APHRS, TSOC, and THRS guidelines. [Eur Heart J 2018;39:1330-1393; J Formos Med Assoc 2016;115:893-952; J Arrhythm 2017;33:345-367]

Bleeding management

“For non-life-threatening major bleeding, reversal agent is generally not necessary … these can be managed with supporting care,” said Chan. [Eur Heart J 2018;39:1330-1393]

For life-threatening major bleeding, idarucizumab is the specific reversal agent for dabigatran while andexanet alpha can be used to reverse factor Xa inhibitors such as apixaban, rivaroxaban, and edoxaban, he stated.