Atrial fibrillation and stroke prevention: brief observations on the last decade

Abstract

Atrial fibrillation (AF) results in a substantial risk of mortality and morbidity from stroke and thromboembolism, and thus, a cornerstone of AF management requires appropriate and effective stroke prevention, which is oral anticoagulation. In the last decade, substantial changes in the landscape of stroke prevention in AF are evident. New knowledge has led to improved treatment options and guidelines have evolved. For example, stroke and bleeding risk assessment has now focused on use of the validated CHA₂DS₂-VASc and HAS-BLED scores, respectively to make clinical decisions. An important clinical practice shift is the initial identification of ‘low-risk’ patients, that is, CHA₂DS₂-VASc score = 0 (male) or 1 (females), who do not need any antithrombotic therapy. Subsequent to this step OAC can be offered to patients with ≥1 stroke risk factors. More recently, the SAMe-TT₂R₂ score has been proposed to aid decision-making, by using simple clinical variables by identifying those AF patients likely to do well on warfarin (SAMe-TT₂R₂ score 0-1) or those more likely to have poor anticoagulation control (SAMe-TT₂R₂ score >2), where a non-vitamin K antagonist oral anticoagulant may be a better option.

Keywords::

• atrial fibrillation
• bleeding
• risk assessment
• stroke

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Erratum

Some facts do not really change much with time. It has long been recognized (and accepted) that atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder, and AF results in a substantial risk of mortality and morbidity from stroke and thromboembolism. A cornerstone of AF management requires appropriate stroke prevention.

Time (and age) increases the risk of developing AF, and with an increasingly ageing population, AF is likely to be more common, especially if we look hard enough (e.g., by a screening program) [1,2]. Age is also a powerful driver of stroke risk, and the risk rises from age 65 upward [3]. Despite these facts being well-recognized, we see that effective stroke prevention (which is oral anticoagulation [OAC]) is suboptimal especially in the elderly and in particularly those at high stroke risk [4,5]. Instead aspirin is prescribed.

Why the paradox? Until a few years ago, if we prescribed OAC, the only drugs available were the vitamin K antagonist (VKA) class of drugs, for example, warfarin [6]. Nonetheless, VKAs required anticoagulation monitoring, and there was considerable variability of the quality of anticoagulation control [7]. Also, VKAs had various food, drug and alcohol restrictions, which led to these drugs being ‘inconvenient’ and considered potentially harmful, due to the risk of bleeding, especially intracranial hemorrhage.

How did clinicians approach VKA use? As the stroke risk associated with AF was not homogeneous, various stroke risk factors derived from nonwarfarin arms of trial cohorts and epidemiological studies have been used to derive stroke risk stratification tools [8,9]. Older schemes ‘artificially’ categorized AF patients into low-, moderate- and high-risk stroke strata, despite stroke risk being a continuum of risk, so that the patients at highest risk of stroke can be identified by these tools to be targeted for warfarin therapy [10]. However, the high-risk patients were consistently undertreated, and as mentioned, stroke risk is a risk continuum rather than ‘neat’ defined categories of ‘low’ or ‘high’ risk [9].

We are now getting better at managing VKAs, recognizing that anticoagulation quality as reflected by the average time in therapeutic range (TTR) matters at lot [11,12]. High mean TTRs are associated with low stroke and bleeding risks when on VKAs. Also, the availability of non-VKA oral anticoagulants (NOACs) that are alternatives to the VKA have revolutionized the landscape of stroke prevention in AF [13–15]. The NOACs offer relative efficacy, safety and convenience compared to VKAs [16,17].

The NOACs were initially called ‘novel’, then ‘new’ OACs, but as these drugs are now available for a few years, they are probably not new nor novel. Despite older publications using the NOAC acronym, more recent confusing terminology has emerged, for example, direct OACs especially Europe and target-specific OACs especially in North America. More recently, there has been an appeal for consensus, to retain the NOAC acronym, to signify ‘non-VKA OACs’, thus allowing consistency with older literature. The possible impact of NOACs on stroke reduction is potentially great, with major implications for healthcare systems [18,19].

In 2012, a major clinical practice shift was introduced – rather than focus on identifying ‘high-risk’ patients, the focused update to the European Society for Cardiology (ESC) guidelines strongly recommends the initial decision step should be the identification of ‘truly low-risk’ patients with AF, that is, those patients who fulfill the criteria of ‘age <65 and lone AF (irrespective of gender)’ – essentially a CHA₂DS₂-VASc score = 0 (males) or 1 (females), and such ‘low-risk’ patients do not need any antithrombotic therapy. Subsequent to that step, patients with AF and ≥1 stroke risk factors can then be offered effective stroke prevention, which essentially is OAC. Depending on healthcare systems, OAC can be given as well managed VKA (as reflected by average TTR ≥70%, as defined in a recent ESC position paper [7]) or one of the NOACs.

New guidelines also recommend bleeding risk assessment using the HAS-BLED score [20]. The latter is well-validated and is the only score to predict intracranial bleeding and outperforms other bleeding risk scores. A high HAS-BLED score (≥3) should not be used as an excuse for stopping OAC, but ‘regular review and follow-up’ is recommended, with attention to potentially reversible bleeding risk factors, for example, concurrent use of antiplatelet drugs in a patient taking OAC [21–23]. Of note, those with a high HAS-BLED score derive a higher net clinical benefit when balancing ischaemic stroke and intracranial bleeding [24,25]. Whilst stroke and bleeding risk track each other, HAS-BLED outperforms the CHA₂DS₂-VASc and CHADS₂ scores for predicting major bleeding [26,27]. Hence, the practice of using the CHA₂DS₂-VASc and CHADS₂ scores as a measure of bleeding risk should be stopped.

Given that well-controlled VKA (TTR ≥70%) or NOACs offer good stroke prevention, a clinical dilemma issue is how to predict those newly diagnosed non-anticoagulated AF patients who would do well on VKA with high TTR, given the costs of the new drugs in some healthcare systems, and avoiding a ‘trial of VKA’ (or a so-called ‘warfarin stress test’). The latter may be putting patients at risk of fatal and devastating strokes, as the stroke rate following the initial introduction of VKA is higher (>70%) in the initial, period reflecting the fact that VKA protection is suboptimal during the period of stabilizing TTR [28].

A recent ESC position paper [7] recommends that the use of the new SAMe-TT₂R₂ score (Table 2) [29] should be considered to aid decision-making, by using simple clinical variables by identifying those AF patients likely to do well on warfarin (SAMe-TT₂R₂ score 0–1) or those more likely to have poor anticoagulation control (SAMe-TT₂R₂ score >2). Those patients with a SAMe-TT₂R₂ score >2 could be better off being started on NOACs as initial therapy, or be ‘flagged up’ for careful review and more aggressive efforts to improve anticoagulation control.

Table 1. Stroke and bleeding risk stratification with the CHA₂DS₂-VASc and HAS-BLED scores.

CHA2DS2-VASc	Score	HAS-BLED	Score
Congestive heart failure/LV dysfunction	1	Hypertension, that is, uncontrolled blood pressure	1
Hypertension	1	Abnormal renal/liver function	1 or 2
Aged ≥75 years	2	Stroke	1
Diabetes mellitus	1	Bleeding tendency or predisposition	1
Stroke/transient ischemic attack/thromboembolism	2	Labile International Normalized Ratio	1
Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque)	1	Age (e.g., >65 years, frail condition)	1
Aged 65–74 years	1	Drugs (e.g., concomitant aspirin or NSAIDs) or alcohol excess/abuse	1
Sex category (i.e., female gender)	1
Maximum score	9		9

Table 2. Definition of the SAMe-TT₂R₂ score.

Acronym	Definitions	Points
S	Sex (female)	1
A	Age (less than 60 years)	1
M	Medical history^†	1
e
T	Treatment (interacting Rx, e.g., amiodarone for rhythm control)	1
T	Tobacco use (within 2 years)	2
R	Race (non-caucasian)	2
	Maximum points	8

^†Two of the following: hypertension, diabetes mellitus, coronary artery disease/myocardial infarction, peripheral artery disease, congestive heart failure, previous stroke, pulmonary disease, hepatic or renal disease.

The last decade has seen lots of changes in our approach to stroke prevention in AF. We look forward to the next decades of personalized management of AF and improving outcomes for our many patients with this common arrhythmia.

Financial & competing interests disclosure

GYH Lip has served as a consultant for Bayer, Astellas, Merck, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Medtronic, Portola and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic and Sanofi Aventis. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.