Actualización en Fibrilación Auricular: de la evidencia a la práctica clínica. 10 de Junio de 2014, 16:30h http://www.secardiologia.es/directos/actualizacionFA.html Introducción: de la investigación a la práctica. ¿Qué cambia en la vida real? Dr. José Ramón González-Juanatey Complejo Hospitalario Universitario de Santiago de Compostela. Presidente SEC Twitter: @JoseJuanatey

2. Translating Evidence into Clinical Practice in CV Medicine
Jones DW et al. Circulation 2008;118:687‒696.
Improving evidence-based medicine
Scientific discovery
Clinical
Investigation
Study Dissemination &
Guideline Formation
Performance
Indicators
Measurement &
Improvement
Patient
Outcomes
“Integrating Quality into the Cycle of
Therapeutic Development”

3. Translating Evidence into Clinical Practice in CV Medicine
Guidelines and Statements
1)Associations and Working Groups.
2)Clinical Practice Guidelines.

4. Translating Evidence into Clinical Practice in CV Medicine
Patients Outcomes
Health National Services
and Hospitals
Guidelines and Statements
Quality of Care Indicators in
Cardiovascular Medicine
Clinical
Conditions and Comobidities
INCARDIO
Benchmarking

5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
CIBAR. Determinantes de Mortalidad
Cardiovascular
GPC: Cumplimiento recomendaciones Guías de Práctica Clínica; DM: diabetes; ICC: insuficiencia cardíaca; IR: insuficiencia renal; EF:
ejercicio físico
1 100,1 3 5 70,70,3 0,5
GPC
ICC
DM
IR
EF
4,4 (2,4-8,1)
1,9 (1,1-3,5)
2,4 (1,3-4,5)
0,43 (0,2-0,8)
HR (IC-95%)
0,47 (0,2-0,9)
Variables

6. Clinical studies vs. real-life data
• Evidence from clinical trials is used to inform guidelines and for regulatory approval
• Real-life data informs on the drug performance and is applicable to a larger proportion of the
population than clinical trial data
Lee S, et al. BMJ Open 2012;2:e001768
Efficacy
Clinical trial
Effectiveness
Real-world data
Objective Does it work under ideal circumstances Does it work under usual
circumstances
Setting/design Control clinical trial Real-world clinical practice
Purpose Regulatory approval Drug performance
Intervention/treatment Fixed regimen Flexible regimen
Comparator Active comparator Active comparator/usual care
Subject Homogeneous/highly selective Heterogeneous/any subjects
Compliance High Low to high
Internal validity High Low
External validity (generalise
to other populations)
Low to medium Medium to high
Pros Well-defined study population
Highly controlled and randomised
Accurate information gathered
Selected, broader subpopulation
from the general population
Can study off-label use
Shorter follow-up time

7. Rationale for real-life studies
Study design
Trial protocol forces uncommon clinical scenarios
Comparison group does not represent current standard of care
Outcomes include less meaningful end points
Patient selection
Biases in the patients who are eligible for a therapy
Biases in patients who are ultimately selected for (or agree to) a therapy
Therapeutic implementation
Complex and multifaceted therapies are challenging to implement
Procedural experience of providers influences outcomes
Environment of the healthcare delivery system
Limited availability of providers or resources
Inadequate levels of reimbursement
Nallamothu B, et al. Circulation 2008;118:1294–1303.

8. Patient population can affect real-life study outcomes
The appropriate patient cohort must be considered:
• Stage of AF is important (as shown by the ATHENA and PALLAS dronedarone
trials)
– ATHENA: patients with paroxysmal or persistent AF
– PALLAS: patients with permanent AF
• Patient characteristics
– Often, younger and healthier patients are chosen for the dronedarone group compared to
the control group, in real-world studies this may be due to appropriate selection based on
labelling
– Dronedarone has shown the best risk/benefit in non-permanent AF patients who are
younger, more active with no or low heart disease
• Patient outcomes
• Study characteristics
Hohnloser SH. J Am Coll Cardiol 2014 [epub ahead of print].
The enrolled AF population in the ATHENA study is broader than the indicated population for dronedarone.
Dronedarone is contraindicated in permanent AF patients.

9. AHA/ACC Guidelines
2014
Rhythm Control in
Paroxy/Pers AF

10. Choice of Oral Antiarrhythmic Drug

11. Large databases on AAD therapy: methodology
Registry Years Study aim Patient characteristics
Number of
AF patients
Clinicalmanagementdatabases
AFFECTS1
(USA)
2005– 2007 Patterns in clinical management AF with stroke risk stroke 1461
ATRIUM2
(Germany)
2009 Management of AF in Germany All stages of AF 3667
CARAF I and II3
(Canada)
1991–2007 Use of AADs in Canada New-onset paroxysmal AF 1400
REALISE-AF4
(Global)
2009– 2010 Worldwide management ≥1 AF episode in 12 months 10523
RECORDAF5
(Global)
2007– 2008 Worldwide management Recent-onset AF 5604
RECORDAF-Asia
Pacific6
2009– 2010 Management across Asia-Pacific Recently diagnosed AF 2629
Outcomesstudies
Department of
Defense7 (US)
2009–2011
Effectiveness of dronedarone
versus other AADs
AAD users with
a history of AF
7404
Clinformatics
MartTM8 (US)
2009–2010
Relationship between outcomes
and AADs
AF/AFL and new users of
AADs
10,455
(AF and AFL)
Swedish AF
cohort9
2010–2012 Investigate risk factors in AF All stages of AF 174,995
1Reiffel JA, et al. Am J Cardiol 2010;105:1122–29; 2Meinertz T, et al. Clin Res Cardiol 2011;100:897–905; 3Andrade JG, et al. Heart Rhythm 2010;7: 1171–7; 4Alam
M, et al. Expert Rev Cardiovasc Ther 2012;10:283–91; 5Camm AJ, et al. J Am Coll Cardiol 2011;58:493–501; 6Amerena J, et al. Am J Cardiol 2012;109:378–82;
7Department of Defense abstract (Boston AF); 8Gao S, et al. JAFIB 2014;6(4):25-33; 9Friberg L, et al. JACC 2014: [epub ahead of print].
AAD, antiarrhythmic drugs; AF, atrial fibrillation; AFL, atrial flutter

12. Clinical management databases: key results
Database First line treatment used Main findings
AFFECTS1
(USA)
Rhythm control: 64%
Rate control: 36%
Rhythm control preference decreased with increased age.
First-line therapy mainly follows 2006 guidelines (86%)
ATRIUM2
(Germany)
Rhythm control: 33% (sometimes
combined with rate control)
Rate control: 75%
Primary care AF patient therapy often conforms to
guidelines but hospitalisation is still high (44%)
CARAF I and II3
(Canada)
Rate control: 52.5%
AF management has significantly changed since 1990:
AAD use has declined since 1994, rate control use peaked
in 2007
REALISE-AF4
(Global)
Rhythm control: 37.2%
Rate control: 57.5%
Significant difference between guidelines and real-life
data. AF is often poorly controlled
RECORDAF5
(Global)
Rhythm control: 54.9%
Rate control: 45.1%
Hospitalisation, not rate or rhythm therapy choice,
mainly drives clinical outcomes in AF
RECORDAF-
Asia Pacific6
Rhythm control: 37%
Rate control: 62%
Recently diagnosed and paroxysmal AF patients are more
frequently prescribed rhythm control. Rate control is
favoured in patients with a history of HF/heart disease
1Reiffel JA, et al. Am J Cardiol 2010;105:1122–29; 2Meinertz T, et al. Clin Res Cardiol 2011;100:897–905; 3Andrade JG, et al. Heart Rhythm
2010;7: 1171–7; 4Alam M, et al. Expert Rev Cardiovasc Ther 2012;10:283–91; 5Camm AJ, et al. J Am Coll Cardiol 2011;58:493–501; 6Amerena
J, et al. Am J Cardiol 2012;109:378–82.
AFL, atrial flutter; CV, cardiovascular; DR, dronedarone; HF, heart failure; TE, thromboembolism