Real-world Evidence From GARFIELD-AF Shows Superior Reduction in Mortality With Non-vitamin K Antagonists Oral Anticoagulants (NOACs) vs. Vitamin K Antagonists (VKAs) in Newly Diagnosed Atrial Fibrill

Munich (ots/PRNewswire) -

- High-risk patients on anticoagulants (AC) for stroke prevention
also have 17% fewer deaths over 2 years of follow-up than
patients who are not treated with AC
- Patients who receive AC plus add-on antiplatelet therapy (AP)
for stroke prevention have a significantly worse prognosis than
patients on AC alone
- More than 70% of patients on NOACs receive the recommended dose,
but prescription of non-recommended doses is associated with a
51% increased risk of death
- A new GARFIELD-AF web-based risk tool was showcased at the
European Society of Cardiology (ESC) Congress 2018 for risk
assessment of patients with AF

A new analysis from the Global Anticoagulant Registry in the
FIELD-Atrial Fibrillation (GARFIELD-AF), the largest multinational
prospective registry in AF, presented today at ESC Congress 2018,
confirms that NOACs are superior to VKAs in reducing 2-year mortality
in higher risk patients (CHA2DS2-VASc score >=2). In this study of
19,134 patients, there were 19% fewer deaths in patients initiated on
NOACs than VKAs at the time of diagnosis of AF (adjusted Hazard Ratio
[HR] 0.81 [95% confidence interval (CI) 0.71, 0.92]; p<0.001). During
a Late-Breaking Science "Registry 2" session,[1] Professor A. John
Camm, St George's, University of London, observed that these data
show the results from randomised controlled trials with NOACs can be
translated to the broader cross-section of patients treated in the
real world. "These real-world data may reflect the impact of poor
VKA control, which was found to be associated with a high risk of
events according our previous research,[2]" he said.

Professor Camm also revealed that there were 17% fewer deaths
(adjusted HR 0.83 [95% CI: 0.75, 0.93; p<0.001]) and 27% fewer
strokes/systemic emboli (adjusted HR 0.73 [95% CI: 0.59, 0.90];
p=0.003) with ACs compared with no AC therapy in higher risk patients
with a CHA2DS2-VASc score >=2[1]: "This new evidence of 26,742
GARFIELD-AF patients analysed over 2 years suggests that AC therapy
has a beneficial effect beyond stroke prevention."

Worse prognosis with AC+AP versus AC alone

In another Late-Breaking Science "Registry 2" presentation from
GARFIELD-AF, Professor Keith Fox, University of Edinburgh, challenged
the use of AC plus add-on antiplatelet (AP) therapy among those
without a clear indication for AP therapy. "In this analysis of
25,815 patients with new onset AF and no prior AP or AC, those who
receive AC and AP therapy at the time of diagnosis of AF have a worse
prognosis than those on AC alone,[3]" said Professor Fox. Overall,
treatment with AC+AP compared to AC alone was associated with
increased risks of major bleeding (adjusted HR 1.45 [95% CI: 0.94,
2.23]) and all-cause mortality (adjusted HR 1.31 [95% CI: 1.05,
1.62]) without a reduction in stroke (adjusted HR 1.60 [95% CI: 1.08,
2.35]).

The detrimental effects on non-recommended NOAC dosing

The global scope of the GARFIELD-AF registry in patients with
newly diagnosed AF also provides an opportunity to evaluate whether
the actual dosing of NOACs in real-life conforms to the approved
dosing regimen (based on country-specific guidelines for each NOAC
for stroke prevention). In a Rapid Fire session at ESC Congress 2018,
Professor John Camm reported that more than 70% of the 10,417
patients received the correct dose of NOAC.[4] Dosing above the
recommended dose was relatively rare (3.6%, overall), and largely
confined to cases where dose-modification was not heeded for
moderate-to-severe chronic kidney disease. For those patients who
received non-recommended low-dose NOAC, all-cause mortality increased
by 51% over the first year of follow-up (adjusted HR: 1.51% [95% CI
1.16-1.96]), compared with patients who received the recommended dose
of NOAC for stroke prevention.

New GARFIELD-AF web-based risk calculator showcased

Now available as a web-based resource, the GARFIELD-AF risk
calculator was showcased at the GARFIELD-AF Satellite Symposium at
ESC.

"We are delighted to announce the availability of the GARFIELD-AF
risk calculator which we believe has the potential to be incorporated
into routine electronic systems," commented Rt Hon Professor the Lord
Kakkar, Director of the Thrombosis Research Institute. The risk
calculator is now available to the GARFIELD-AF research community and
will be made generally available early next year.

In 2016, Professor Keith Fox and colleagues on behalf of the
GARFIELD-AF investigators published results on the GARFIELD-AF risk
calculator for assessing the risk of death, stroke/systemic embolism
and major bleeding in patients over the first year after the
diagnosis of AF.[5] This tool had superior predictive value compared
to CHA2DS2-VASc for predicting stroke and death. It was also at least
as good as HAS-BLED for predicting major bleeding in patients who
received AC for stroke prevention. The value of the GARFIELD-AF risk
calculator was validated using contemporary data from the ORBIT II
registry from the USA.

To view the eight GARFIELD-AF data presentations at the ESC
Congress 2018 and a video recording of the TRI Satellite Symposium,
please visit: http://www.garfieldregistry.org

About the GARFIELD-AF registry

GARFIELD-AF is a worldwide observational programme that aims to
enhance the breadth and depth of understanding of stroke prevention
in atrial fibrillation (AF), ultimately informing strategies to
improve patient outcomes, safety and utilisation of healthcare
resources.

It offers a unique opportunity to obtain a comprehensive and
contemporary description of the spectrum of patients with AF and
their management worldwide as they evolve over time. The registry is
important in bridging the gap between research and clinical practice,
serving to increase awareness of the importance of thrombosis and its
treatment.

GARFIELD-AF recruited patients with newly diagnosed nonvalvular AF
and at least one risk factor for stroke. A total of 57,262 patients
were recruited from 1352 centres in 35 countries worldwide, including
the Americas, Europe, Africa and Asia-Pacific, over five sequential
cohorts. Follow-up is over a minimum of 2 years and up to 8 years
after diagnosis, to create a comprehensive database of treatment
decisions and outcomes in everyday clinical practice.

GARFIELD-AF is a pioneering, independent academic research
initiative led by an international steering committee under the
auspices of the Thrombosis Research Institute (TRI), London, UK.

Contemporary understanding of AF is based on data gathered in
controlled clinical trials. Whilst essential for evaluating the
efficacy and safety of new treatments, these trials are not
representative of everyday clinical practice and, hence, uncertainty
persists about the real-life burden and management of this disease.
GARFIELD-AF seeks to provide insights into the impact of
anticoagulant therapy on thromboembolic and bleeding complications
seen in this patient population. It will provide a better
understanding of the potential opportunities for improving care and
clinical outcomes amongst a representative and diverse group of
patients and across distinctive populations. This should help
physicians and healthcare systems to appropriately adopt innovation
to ensure the best outcomes for patients and populations.

The registry started in December 2009. Four key design features of
the GARFIELD-AF protocol ensure a comprehensive and representative
description of AF; these are:

- Five sequential cohorts of prospective, newly diagnosed patients,
facilitating comparisons of discrete time periods and describing
the evolution of treatments and outcomes;
- Investigator sites that are selected randomly within carefully
assigned national AF care setting distributions, ensuring that the
enrolled patient population is representative;
- Enrolment of consecutive eligible patients regardless of therapy to
eliminate potential selection bias;
- Follow-up data captured for a minimum of 2 and up to 8 years after
diagnosis, to create a comprehensive database of treatment
decisions and outcomes in everyday clinical practice.

Included patients must have been diagnosed with nonvalvular AF
within the previous 6 weeks and have at least one risk factor for
stroke; as such, they are potential candidates for anticoagulant
therapy to prevent blood clots leading to stroke. It is left to the
investigator to identify a patient's stroke risk factor(s), which
need not be restricted to those included in established risk scores.
Patients are included whether or not they receive anticoagulant
therapy, so that the merit of current and future treatment strategies
can be properly understood in relation to patients' individual risk
profiles.

The GARFIELD-AF registry is funded by an unrestricted research
grant from Bayer AG, Berlin, Germany.

For more information, visit our website:
http://www.garfieldregistry.org.

The burden of AF

Up to 2% of the global population has AF,[6] including around 8.8
million people in Europe[7] and 5-6.1 million in the United
States.[8] It is estimated that its prevalence will at least double
by 2050 as the global population ages.[8] AF is associated with a
five-fold increase in stroke risk, and one out of five strokes is
attributed to this arrhythmia.[6] Ischaemic strokes related to AF are
often fatal, and those patients who survive are left more frequently
and more severely disabled and have a greater risk of recurrence than
patients with other causes of stroke.[6] Hence, the risk of mortality
from AF-associated stroke is doubled and the cost of care is 50%
higher.[6]

AF occurs when parts of the atria emit uncoordinated electrical
signals. This causes the chambers to pump too quickly and
irregularly, not allowing blood to be pumped out completely.[9] As a
result, blood may pool, clot and lead to thrombosis, which is the
number one cardiovascular killer in the world.[10] If a blood clot
leaves the left atrium, it could potentially lodge in an artery in
other parts of the body, including the brain. A blood clot in an
artery in the brain leads to a stroke; 92% of fatal strokes are
caused by thrombosis.[10] Stroke is a major cause of death and
long-term disability worldwide - each year, 6.5 million people
die[11] and 5 million are left permanently disabled.[12] People with
AF also are at high risk for heart failure, chronic fatigue and other
heart rhythm problems.[13]

About the TRI

The TRI is dedicated to bringing new solutions to patients for the
detection, prevention and treatment of blood clots. The TRI's goal is
to advance the science of real-world enquiry so that the value of
real-world data is realised and becomes a critical link in the chain
of evidence. Our pioneering research programme, across medical
disciplines and across the world, continues to provide breakthrough
solutions in thrombosis.

For more information, visit: http://www.tri-london.ac.uk/.

Camm AJ, et al. Comparative effectiveness of oral anticoagulants
in everyday practice. Late Breaking Registry Results 2 ESC Congress
2018. Nr 5876

1. Haas S, et al. Quality of vitamin K antagonist control and 1-year
outcomes in patients with atrial fibrillation: a global
perspective from the GARFIELD-AF registry. PLoS One 2016; 11:
e0164076
2. Fox KAA, et al. Adverse one-year outcome for patients newly
treated with oral anticoagulants plus antiplatelet therapy after
a diagnosis of atrial fibrillation. Results from the GARFIELD-AF
prospective registry. Late Breaking Registry Results 2 ESC
Congress 2018. Nr 5878.
3. Camm AJ, et al. The effect of non-recommended dosing of
non-vitamin K antagonist oral anticoagulants (NOACs) on 1-year
mortality in patients with newly diagnosed AF. Results from the
GARFIELD-AF registry. Rapid Fire Session Atrial Fibrillation -
detection, treatment, outcomes. ESC Congress 2018 Nr 1354.
4. Fox KAA et al. Improved risk stratification of patients with
atrial fibrillation: an integrated GARFIELD-AF tool for the
prediction of mortality, stroke and bleed in patients with and
without anticoagulation. BMJ Open. 2017;7: e017157.
5. Camm AJ, et al. Guidelines for the management of atrial
fibrillation: The Task Force for the Management of Atrial
Fibrillation of the European Society of Cardiology (ESC). Eur
Heart J 2010; 31(19):2369-429.
6. Krijthe B P, Kunst A, et al. Projections on the number of
individuals with atrial fibrillation in the European Union, from
2000 to 2060. Eur Heart J 2013; 34:2746-51.
7. Colilla S, Crow A, Petkun W, et al. Estimates of current and
future incidence and prevalence of atrial fibrillation in the
U.S. adult population. Am J Cardiol 2013; 112(8):1142-7.
8. National Heart, Lung, and Blood Institute. What is Atrial
Fibrillation? Available at:
http://www.nhlbi.nih.gov/health/health-topics/topics/af/. [Last
accessed: August 9 2018].
9. World Thrombosis Day. Know Thrombosis. Available at:
http://www.worldthrombosisday.org/issue/thrombosis/. [Last
accessed: 9 August 2018].
10. World Stroke Organization. World Stroke Campaign. Available at:
http://www.worldstrokecampaign.org/. [Last accessed: 9 August
2018].
11. Stroke Centre. Stroke Statistics. Available at: http://www.stroke
center.org/patients/about-stroke/stroke-statistics/. [Last
accessed: 9 August 2018].
12. American Heart Association. Why Atrial Fibrillation (AF or AFib)
Matters. Available at: http://www.heart.org/HEARTORG/Conditions/A
rrhythmia/AboutArrhythmia/Why-Atrial-Fibrillation-AF-or-AFib-Matt
ers_UCM_423776_Article.jsp. [Last accessed: 9 August 2018].

ots Originaltext: Thrombosis Research Institute
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Charlotte Shyllon
CShyllon@tri-london.ac.uk
+44(0)7415-858-411

Rae Hobbs
RHobbs@tri-london.ac.uk
+44(0)7753-825-217

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