Share this Article
Copyright: © Singapore Medical Association
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. In 2008, Yap et al estimated that the overall AF prevalence in Singapore was 1.5%, and this would have increased over the years with our ageing population.(1) AF results in a twofold rise in mortality and a fivefold increase in the risk of stroke. The overall annual incidence of AF-associated ischaemic stroke in Asia ranged from 1.3% in Japan to 15.4% in the Far East and Southeast Asia.(2,3) Ischaemic stroke in AF patients typically causes a greater degree of disability and higher mortality. Consequently, AF is increasingly recognised as a significant public health concern, given its negative impact on morbidity and mortality.
The cornerstone of stroke prevention in AF is anticoagulation. The Asia Pacific Heart Rhythm Society (APHRS) consensus guideline recommends the CHA2DS2-VASc score for the prediction of stroke risk in Asians with non-valvular AF.(4) Oral anticoagulation is recommended for males with a CHA2DS2-VASc score ≥ 1 and females with a score ≥ 2, with non-vitamin K antagonist oral anticoagulants (NOACs) being preferred over warfarin.
In this issue of the Singapore Medical Journal, Krittayaphong et al highlighted the problem of suboptimal anticoagulation therapy with warfarin for stroke prevention in AF patients in Thailand.(5) Due to the higher costs of NOACs, warfarin remains a widely prescribed oral anticoagulant in Asia, including Singapore. The efficacy and safety of warfarin is dependent on the quality of international normalised ratio (INR) control, as measured by the time in therapeutic range (TTR). A TTR < 60% reflects poor quality of warfarin treatment and is linked to increased patient mortality and adverse outcomes. Bernaitis et al reported an overall mean TTR of 58% in AF patients receiving warfarin in a tertiary cardiac centre in Singapore, with a TTR in Chinese, Malays and Indians of 58.7%, 55.2% and 49.7%, respectively.(6) Kew et al showed that up to 61.3% of AF patients at high risk of cardioembolic stroke were not prescribed warfarin upon discharge from a tertiary cardiology unit in Singapore.(7) The most common reasons for withholding anticoagulation were physicians’ decisions, patients’ turning it down and history of bleeding. Aribou et al debunked some fears that physicians in Singapore faced during anticoagulation prescribing, such as advanced age, fall and bleeding risks, providing evidence that these concerns were largely unfounded.(8)
The issue of having poor-quality anticoagulation with warfarin is not unique to Singapore and Thailand. The Global Anticoagulant Registry in the Field-Atrial Fibrillation revealed that patients from Eastern and Southeastern Asian countries recorded significantly lower TTR (31.1% vs. 54.1%) compared to the rest of the world.(9) To help identify Asian patients who are likely to have suboptimal TTR, the APHRS consensus guideline recommends the use of the SAMe-TT2R2 score (i.e. sex, age, medical history, treatment, tobacco use, race).(4) In Singapore, Bernaitis et al validated the SAMe-TT2R2 score in a retrospective study, reporting that a score ≥ 3 predicted a TTR < 60%.(6) Such patients were less likely to achieve good quality anticoagulation with warfarin, and alternative anticoagulants such as NOACs should be considered.
The use of NOACs in Singapore has increased steadily since their introduction in 2011. Compared to warfarin, the main advantages of NOACs are fewer interactions with other drugs and foods, reduced risk of intracranial bleeding, quick onset and offset of action that obviates the need for bridging therapy during anticoagulation interruption, and no requirement for regular INR monitoring. Reversal agents have also become available: andexanet alfa for Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and idarucizumab for the direct thrombin inhibitor dabigatran. In a meta-analysis comparing Asians and non-Asians, Wang et al reported that standard-dose NOACs were more effective in reducing stroke or systemic embolism and resulted in significantly less major bleeding in Asians.(10) The efficacy and safety of NOACs in AF patients in Singapore have been described in two local studies.(11,12)
In line with international guidelines, NOACs should therefore be the anticoagulant of choice in Singapore for stroke prevention in patients with non-valvular AF.(4,13,14) The main impediment to NOAC use is higher prices when compared with warfarin. However, the introduction of government subsidies has helped to offset the drug costs, which may decrease with the possible introduction of generic versions in 4–5 years. Warfarin still has a role in special AF patient populations, namely those with Stage 4 and 5 chronic kidney disease, moderate to severe mitral stenosis and patients with mechanical heart valves.(4,13,14) A SAMe-TT2R2 score ≥ 3 can help to identify patients who will require more frequent clinic reviews, INR monitoring, education and counselling to ensure optimal TTR.
1. Yap KB, Ng TP, Ong HY. Low prevalence of atrial fibrillation in community-dwelling Chinese aged 55 years or older in Singapore: a population-based study. J Electrocardiol 2008; 41:94-8.
2. Suzuki S, Yamashita T, Okumura K, et al. Incidence of ischemic stroke in Japanese patients with atrial fibrillation not receiving anticoagulation therapy--pooled analysis of the Shinken Database, J-RHYTHM Registry, and Fushimi AF Registry. Circ J 2015; 79:432-8.
3. Guo Y, Lip GY, Apostolakis S. The unmet need of stroke prevention in atrial fibrillation in the far East and South East Asia. Malays J Med Sci 2012; 19:1-7.
4. Chiang CE, Okumura K, Zhang S, et al. 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation. J Arrhythm 2017; 33:345-67.
5. Krittayaphong R, Winijkul A, Pirapatdit A, et al; COOL-AF Investigators.SAMe-TT2R2 score for prediction of suboptimal time in therapeutic range in a Thai population with atrial fibrillation. Singapore Med J 2020; 61:641-6.
6. Bernaitis N, Ching CK, Chen L, et al. The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) score predicts warfarin control in a Singaporean population. J Stroke Cerebrovasc Dis 2017; 26:64-9.
7. Kew GS, Tan M, Lim TW. Poor adherence to anticoagulation guidelines in patients with non-valvular atrial fibrillation treated in a tertiary cardiology unit. Heart Asia 2015; 7:18-22.
8. Aribou ZM, Mondry A. Anticoagulation needs in Asians with atrial fibrillation: a mythbuster. Ann Acad Med Singapore 2014; 43:275-8.
9. Oh S, Goto S, Accetta G, et al; GARFIELD-AF Investigators. Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: real-world data from the GARFIELD-AF registry. Int J Cardiol 2016; 223:543-7.
10. Wang KL, Lip G, Lin SJ, Chiang CE. Non-vitamin K antagonist oral anticoagulants for stroke prevention in Asian patients with nonvalvular atrial fibrillation: meta-analysis. Stroke 2015; 46:2555-61.
11. Chan LX, Wong YM, Chia PL, Kek ZL. A single institution's experience with using dabigatran, rivaroxaban and warfarin for prevention of thromboembolism in atrial fibrillation. Proc Singapore Healthc 2017; 27:20-5.
12. Wee XT, Ho LM, Ho HK, et al. Incidence of thromboembolic and bleeding events in patients with newly diagnosed nonvalvular atrial fibrillation: an Asian multicenter retrospective cohort study in Singapore. Clin Cardiol 2017; 40:1218-26.
13. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:104-32.
14. Kirchhof P, Benussi S, Kotecha D, et al; ESC Scientific Document Group. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37:2893-962.