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Atrial Fibrillation
Research Review
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In this issue:
>>Biomarker-based ABC stroke risk
score for AF
>>Anticoagulation with apixaban
during AF catheter ablation
>>Cryoballoon vs. RF ablation for
persistent AF
>>Silent cerebral events after RF
ablation: impact of anticoagulation
strategy
>>Effectiveness and safety of NOACs
vs. warfarin in AF
>>Polypharmacy and effects of
apixaban vs. warfarin in AF
>>Obesity and AF after cardiac
surgery
>>Lone AF: prevalence, incidence and
prognosis
>>Intracerebral haematoma during
warfarin vs. NOACs
>>Use of aspirin in AF patients at risk
for stroke
Abbreviations used in this issue:
AF = atrial fibrillation; CV = cardiovascular; HR = hazard ratio;
INR = international normalised ratio; LMWH = low-molecular-weight heparin;
MRI = magnetic resonance imaging; NOAC = nonvitamin K oral anticoagulant;
RF = radiofrequency; TIA = transient ischaemic attack;
VKA = vitamin K antagonist.
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Issue 31 - 2016
Welcome to issue 31 of Atrial Fibrillation Research Review.
A paper reporting the success of a novel biomarker-based stroke prediction score, ABC, for use in patients
with AF begins this issue. NOACS feature in a number of the other papers selected. German researchers have
reported that continuing NOACs and VKAs during RF catheter ablation of AF seems to be safe and significantly
reduces the occurrence of postablation silent cerebral events, and research out of Denmark has compared the
safety and effectiveness of NOACs versus warfarin in AF. A post hoc analysis of ARISTOTLE data has compared
the impact polypharmacy has on the treatment effects of apixaban and warfarin, and Japanese researchers
found that intracerebral haemorrhages occurring during NOAC therapy were of smaller volume, had a slower
expansion rate and resulted in less mortality than when they occurred during warfarin therapy.
I hope you find the papers in this issue useful in your practice and I welcome your comments and feedback.
Kind Regards,
Dr Andrei Catanchin
[email protected]
The ABC (age, biomarkers, clinical history) stroke risk score: a
biomarker-based risk score for predicting stroke in atrial fibrillation
Authors: Hijazi Z et al., on behalf of the ARISTOTLE and STABILITY Investigators
Summary: These researchers developed and validated a new ABC (Age, Biomarkers, Clinical history) stroke
risk score to assist in stroke risk prediction in patients with AF. Biomarker levels were measured at baseline
and during median follow-up of 1.9 years in 14,701 patients with AF. Biomarkers and clinical variables that
significantly contributed to predicting stroke or systemic embolism were assessed by Cox regression, and each
variable was given a weight proportional to the model coefficients. External validation was undertaken in 1400
patients with AF who were followed for a median 3.4 years. Prior stroke/TIA, N-terminal pro-B-type natriuretic
peptide level, cardiac troponin high-sensitivity level and age emerged as the most important predictors and were
included in the ABC stroke risk score. In both the derivation and validation cohorts, the c-indices of the ABC
stroke risk score were significantly higher than for CHA 2DS2VASc (0.68 vs. 0.62 and 0.66 vs. 0.58, respectively).
Comment: To try to keep risk scoring systems user-friendly, and because of lack of consensus and
standardisation with respect to biomarkers, only clinical factors feature in guidelines and scoring systems
(CHA 2DS2VASc, and CHADS2 before it). Elevated biomarkers refine our evaluation and identify those patients
with equal CHA 2DS2VASc scores but at significantly higher risk of thromboembolism. Note that age >75 years
and prior stroke/TIA are critical components.
Reference: Eur Heart J 2016;37(20):1582–90
Abstract
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Apixaban for periprocedural anticoagulation during catheter
ablation of atrial fibrillation
Authors: Blandino A et al.
Summary: This was a systematic review and meta-analysis of one randomised and five nonrandomised
trials reporting on the use of apixaban in the context of AF ablation. The trials included 668 apixaban
recipients and 1023 warfarin recipients. No heterogeneity in any of the outcome comparisons was
evident. There were no deaths reported. Compared with warfarin, apixaban was not associated with
an increased risk of thromboembolic events (odds ratio 1.10 [95% CI 0.24–5.16]), major bleeding
(1.56 [0.59–4.13]), cardiac tamponade (1.69 [0.52–5.54]), minor bleeding (0.96 [0.58–1.59]) or
the composite of death, thromboembolic events or bleeding (1.03 [0.65–1.64]).
Comment: As with other recent reports, this paper (specific to apixaban) shows that ablation
on an uninterrupted NOAC appears safe when compared to ablation on uninterrupted warfarin
(which is currently standard of care in many centres).
Reference: J Interv Card Electrophysiol; Published online May 23, 2016
Abstract
Outcomes after cryoballoon or radiofrequency ablation for
persistent atrial fibrillation
Authors: Boveda S et al.
Summary: This prospective propensity-score matched study included 59 consecutive patients with
persistent AF who had undergone cryoballoon ablation, each matched to a patient treated with RF;
mean follow-up was 15.6 months. The proportions of patients presenting with atrial arrhythmia
relapse after a blanking period of 3 months were similar between the cryoballoon and RF groups
(40.7% vs. 45.8 % [p=0.15]), despite 52.5% of the RF group adding additional complex fractionated
atrial electrogram ablation, as well as left atrial linear ablation in over two-thirds (roof line and
mitral isthmus in 67.8% and 32.2%, respectively). The only predictor of relapse on multivariate Cox
regression was AF duration in years (HR 1.10 [95% CI 1.01–1.10]). RF ablation was associated with
a numerically, but nonsignificantly, lower complication rate than ablation (6.8% vs. 10.2% [p=0.51]).
Impact of periprocedural anticoagulation
strategy on the incidence of new-onset
silent cerebral events after radiofrequency
catheter ablation of atrial fibrillation
Authors: Müller P et al.
Summary: This research sought to establish whether periprocedural
oral anticoagulation management affects the incidence of new-onset
silent cerebral events post-RF catheter ablation in 192 prospectively
enrolled consecutive patients with symptomatic paroxysmal (n=80) or
persistent AF. The periprocedural anticoagulation strategies assessed
were: i) uninterrupted use of an NOAC (n=64); ii) interrupted use of
an NOAC (n=42); iii) continuation of a VKA with INR 2.0–3.0 (n=43);
and iv) VKA discontinuation bridged with LMWH (n=43). New silent
cerebral events were detected by cerebral MRI, performed 1–2 days
after RF catheter ablation, in 21.4% of the patients overall, with rates
of 12.5%, 35.7%, 18.6% and 23.3% in the respective aforementioned
anticoagulation groups. A multivariable logistic regression analysis
revealed that persistent AF and periprocedural oral anticoagulation
discontinuation (i.e. interrupted NOAC, and VKA discontinuation bridged
with LMWH) independently predicted silent cerebral events.
Comment: Asymptomatic cerebral emboli/new MRI lesions
are well known after all interventional procedures in the central
arterial circulation and are not generally related to stroke/TIA
risk. Nevertheless, some techniques or procedures carry a higher
risk of adverse cardiac events than others, and uninterrupted
anticoagulation clearly reduced events in this (small) study.
Reference: J Interv Card Electrophysiol; Published online
Mar 28, 2016
Abstract
Comment: Along with FIRE and ICE in the previous issue of Atrial Fibrillation Research Review, this
much smaller report specific to persistent AF patients showed similar efficacy and complications
between RF and cryoablation approaches. As expected, RF ablation took longer and cryoablation
carried a higher risk of phrenic nerve injury.
Reference: J Interv Card Electrophysiol; Published online May 18, 2016
Abstract
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References: 1. PRADAXA Product Information. 2. PRAXBIND Product Information. 3. Therapeutic Goods Administration. Reasons for scheduling delegate’s final decisions NCEs (Medicines) - April 2016. 1.6 Idarucizumab. Available at: https://www.tga.gov.au/book-page/16-idarucizumab. Accessed 3 May 2016. Further
information is available on request from Boehringer Ingelheim. Pradaxa® and Praxbind® are registered trademarks of Boehringer Ingelheim Pty
Limited, ABN 52 000 452 308, 78 Waterloo Road, North Ryde NSW 2113. AUS/PRA-161236 S&H BOIPX0058-AFRR-HP. June 2016.
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BOIPX0058_AFRR_HP_[f].indd 1
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Comparative effectiveness and safety
of non-vitamin K antagonist oral
anticoagulants and warfarin in patients
with atrial fibrillation
Authors: Larsen TB et al.
Summary: The effectiveness and safety of NOACs versus warfarin
were explored in anticoagulant-naïve patients with nonvalvular AF,
identified from three Danish databases, in this propensity-weighted
observational cohort study; there were 35,436 warfarin recipients,
12,701 dabigatran 150mg recipients, 7192 rivaroxaban 20mg
recipients and 6349 apixaban 5mg recipients. Compared with
warfarin, there was no significant difference for ischaemic
stroke/systemic embolism risk for dabigatran or apixaban, but
rivaroxaban was associated with a lower annual rate (3.0% vs.
3.3%; HR 0.83 [95% CI 0.69–0.99]), whereas for the annual risk
of death, apixaban and dabigatran were associated with lower
risks (5.2% and 2.7% vs. 8.5%; 0.65 [0.56–0.75] and 0.63
[0.48–0.82], respectively), but rivaroxaban was not. Similarly,
apixaban and dabigatran (but not rivaroxaban) were associated
with lower annual rates of any bleeding than warfarin (3.3% and
2.4% vs. 5.0%).
Comment: We are seeing more and more real-world data
emerging examining NOAC use and outcomes. As expected,
the NOACs compared favourably with warfarin. Rivaroxabantreated patients had significantly less ischaemic stroke/systemic
embolism, while apixaban/dabigatran-treated patients had
lower mortality and less bleeding.
Reference: BMJ 2016;353:i3189
Abstract
Polypharmacy and effects of apixaban
versus warfarin in patients with atrial
fibrillation
Authors: Focks JJ et al.
Summary: This post hoc analysis of ARISTOTLE trial participants,
who had been randomised to apixaban 5mg twice daily (n=9120)
or warfarin (target INR 2.0–3.0; n=9081), looked at outcomes
according to concomitant drug use at baseline. The median
number of drugs used per participant was six, with 76.5%
receiving ≥5 drugs. Older patients, women and participants from
the US had greater numbers of concomitant drugs. The number
of concomitant drugs increased as comorbidities increased
across groups, as did the proportions of participants receiving
agents that interact with warfarin or apixaban. Higher numbers
of concomitant medications were also associated with greater
mortality, stroke/systemic embolism rates and major bleeding.
Apixaban and warfarin were associated with consistent reductions
in the relative risk of stroke/systemic embolism regardless of the
number of concomitant drugs (p=0.82 for interaction), whereas
apixaban was associated with a smaller reduction in major
bleeding risk than warfarin as the number of concomitant drugs
increased (p=0.017 for interaction). Outcomes and consistent
treatment effects were similar for apixaban versus warfarin in
participants receiving interacting (potentiating) drugs.
Comment: Perhaps not surprisingly, the number of concurrent
medications is related to age and number of comorbidities (as
well as female sex and living in the US), and carries higher
mortality, stroke rate and major bleeding. The safety/efficacy
profile of apixaban versus warfarin was preserved, although
the reduction in major bleeding was less pronounced in the
highest risk groups.
Obesity and postoperative atrial fibrillation in patients undergoing
cardiac surgery
Authors: Phan K et al.
Summary: This was a systematic review and meta-analysis of studies reporting data on the association
between obesity and AF following cardiac surgery. Compared with nonobese individuals, those who
were obese were significantly more likely to experience postoperative AF (p=0.006). However,
significant heterogeneity was detected among the included studies. Compared with no postoperative
AF, the occurrence of postoperative AF significantly increased the risks of stroke (p<0.0001), death
within 30 days (p=0.005) and respiratory complications (p<0.00001), but no significant association
was seen between postoperative AF and myocardial infarction (p=0.79).
Comment: We know obesity is generally associated with higher incident/prevalent AF, more
symptomatic AF, more persistent AF, more challenging rhythm control including reduced efficacy
of AF ablation and higher arrhythmia recurrence. This review clearly associates obesity with AF
postcardiac surgery and reminds us of the further link to stroke and mortality. We may have
another reason to encourage weight loss before elective surgery in the obese.
Reference: Int J Cardiol 2016;217:49–57
Abstract
Atrial fibrillation without comorbidities: prevalence, incidence and
prognosis (from the Framingham Heart Study)
Authors: Kim E-J et al.
Summary: These authors compared participants from the Framingham Heart Study with AF without
comorbidities (‘lone’ AF) with participants with typical AF and matched individuals without AF. Of 10,311
participants, 1961 had incident AF, of whom 173 had ‘lone’ AF, giving a cohort prevalence of 1.7%
and an annual incidence of 0.5 per 1000 person-years. During a median 9.7 years of follow-up,
the mortality rate for the participants with AF without comorbidities was 79.2% and their CV event
rate was 81.5%. Compared with participants with typical AF, those with AF without comorbidities
has significantly lower risks of death (HR 0.67 [95% CI 0.55–0.81]) and total CV events (0.66
[0.55–0.80]), but their risks were still greater than those of individuals without AF (1.43 [1.18–1.75]
and 1.73 [1.39–2.16], respectively).
Comment: This report reminds us that although lone AF is ‘safer’ than non-lone AF, it is by
no means benign, and is associated with adverse CV outcomes and mortality compared with
non-AF individuals.
Reference: Am Heart J 2016;177:138–44
Abstract
Atrial Fibrillation
Research Review
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Independent commentary by Dr Andrei Catanchin, a cardiologist/electrophysiologist
specialising in the management of AF and other arrhythmias in private practice in Melbourne.
Dr Catanchin has a particular expertise in the management of AF and other rhythm disorders.
He performs catheter ablation for AF and other arrhythmias, implants pacemakers and ICDs
(defibrillators) and his research interests include alternatives to warfarin in AF management.
This publication is endorsed by ACN according to our Continuing
Professional Development Endorsed Course Standards. It has been
allocated 1 CPD hour(s) according to the Nursing and Midwifery
Board of Australia – Continuing Professional Development Standard.
For more information click here
Reference: BMJ 2016;353:i2868
Abstract
www.researchreview.com.au
a RESEARCH REVIEW publication
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Intracerebral hematoma occurring during
warfarin versus non-vitamin K antagonist
oral anticoagulant therapy
Authors: Takahashi H et al.
Summary: These authors compared cases of nonvalvular AF on
dabigatran (n=4), rivaroxaban (n=2) or apixaban (n=7) therapy
admitted for intracerebral haemorrhage over a 3-year period with
65 comparable patients who experienced intracerebral haemorrhage
while on warfarin therapy. Clinical features were similar between the
NOAC versus warfarin recipients, including CHADS2 and HAS-BLED
scores (2.62 vs. 2.62 and 1.09 vs. 1.00, respectively). Compared
with warfarin recipients, a greater proportion of NOAC recipients
had an intracerebral haemorrhage volume of <30mL (84.6% vs.
53.8% [p=0.0106]), and they also had a lower hospital mortality
rate (7.7% vs. 41.5% [p=0.0105]) and better modified Rankin Scale
score (3.2 vs. 4.5 [p=0.0057]). Haematoma expansion was seen in
seven warfarin recipients.
Comment: We know from each of the major NOAC trials that
patients taking NOACs have significantly less intracerebral
haemorrhage than those taking warfarin and the overall incidence
is very low. Bearing in mind that the Japanese have substantially
higher rates of intracerebral haemorrhage than other populations
(regardless of anticoagulant regimen used), this real-world analysis
shows intracerebral haemorrhages in NOAC recipients were
smaller, progressed less and carried lower mortality than those
on warfarin.
Aspirin instead of oral anticoagulant prescription in atrial
fibrillation patients at risk for stroke
Authors: Hsu JC et al.
Summary: Factors associated with prescription of aspirin alone versus oral anticoagulation in
‘real-world’ US registry outpatients with AF at intermediate-to-high risk of thromboembolism
were identified in this paper. Among two cohorts of patients with CHADS2 ≥2 (n=210,380) and
CHA 2DS2VASc ≥2 (n=294,642), 38.2% and 40.2%, respectively, were treated with aspirin alone,
while 61.8% and 59.8% received warfarin or an NOAC. A multivariable analysis revealed that
factors associated with prescription of aspirin alone were hypertension, dyslipidaemia, coronary
artery disease, prior myocardial infarction, unstable and stable angina, recent coronary artery
bypass graft and peripheral arterial disease, and factors associated with prescription of oral
anticoagulation were male sex, higher body mass index, prior stroke/TIA, prior systemic embolism
and congestive heart failure.
Comment: Although aspirin has no role in AF management, we know it remains frequently
used as an alternative to anticoagulation (40% of these 300,000 patients). Presumably due to
persisting misconceptions, or trying to avoid combination therapy (aspirin plus anticoagulation),
aspirin was more likely the chosen therapy in patients with significant vascular disease or
other strong indication for its use.
Reference: J Am Coll Cardiol 2016;67(25):2913–23
Abstract
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Reference: Am J Cardiol 2016;118(2):222–5
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STREAMLINED AUTHORITY CODE 4269 for stroke prevention in non‑valvular atrial fibrillation
PBS Information: PRADAXA: Authority required (STREAMLINED) for the prevention of stroke or systemic embolism in patients
with non‑valvular atrial fibrillation and one or more risk factors for developing stroke or systemic embolism. Authority required
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This product is not listed on the PBS for treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE), or for the prevention of
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ABN 52 000 452 308, 78 Waterloo Road, North Ryde NSW 2113. AUS/PRA‑161236 S&H BOIPX0058‑AFRR‑HP‑P. June 2016.
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