Download Rate control versus rhythm control in NSTEMI.

Rate Control versus Rhythm
Control in NSTEMI
Gulmira Kudaiberdieva, MD, FESC
Adana, Turkey
Conflict of interest: None to declare
Istanbul - 2012
OUTLINE

Significance of AF in ACS

Prognostic value of AF in NSTEMI

Rate vs rhythm control in AF

Rate vs rhythm control in ACS/NSTEMI

ESC AF 2010 guideline`s recommendations
Significance of AF in ACS
 AF is a frequently encountered arrhythmia in the setting of ACS
 Population-based studies demonstrated that the incidence of AF in the
setting of AMI and ACS tended to increase up to 13.3% during last
decade
 Incidence of AF in the setting of NSTE-ACS varies between 6.2 and
7.9% and it has a worse impact on the clinical course and prognosis of
the disease
 Appropriate treatment strategies of AF in the setting of ACS might
modify its unfavorable impact on prognosis
Atrial Fibrillation in NSTEMI
RCT/META-ANALYSIS
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PURSUIT
•
Gusto IIB
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IMPACT II
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REGISTRY/SURVEY
•
GRACE registry
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•
PRAXIS
•
ACACIA
PARAGON
Meta-analysis
(Lopes et al. Heart 2008)
RICO
•
•
•
FAST-MI
PROGNOSTIC SIGNIFICANCE OF AF IN NSTEMI
Study
Study type/
Population
AF
End-point
Outcome
GRACE
Registry
21785 ACS pts
New -6.2%
Prior-7.9%
In-hospital
Death
OR 1.65 (1.3-2.09)
-
RCT
9432 pts, NSTEMI
New – 6.4%
Death
30-d
6-m
HR 7.01 (5.36-9.16)
HR 4.46 (3.57-5.52)
Lopez et al
(Heart 2008)
Meta-analysis
(PURSUIT, PARAGON, Gusto
II B, SYNERGY)
36405 NSTE-ACS pts
Any AF
6.4%
<7-d
1-year
HR 1.67 (1.41-1.99)
ACACIA
Lau et al.
Registry
STEMI - 755
HR NSTE ACS – 1942
IR NSTE-ACS -696
New AF
6.5%
4.6%
1.6%
1-year
Comp: death,
MI, stroke
Survey, prospective
NSTEMI 504 pts
AF<24h
In hospital
Death/VA
(Am J Cardiol 2003;92:1031–1036)
PURSUIT (Am J Cardiol 2001; 88: 76-9.)
(Am J Cardiol 2009;104:1317–23)
RICO
(Heart 2005;91:369-70)
PRAXIS
(Am J Cardiol 2012;110:217–221)
ACS 2335 pts
Prev known AF:
Perm
pers- parox
New-onset:
Admission
In-hospital
HR 1.1 (0.67-2.83)
HR 2.0 (1.15-3.48)
HR 3.9 (1.21-12.7)
OR 2.2, p<0.001
10-year
Mortality
6.4%
2.3%
78%
69%
2.3%
7.88%
68%
53.2
Adj ORs for in-hospital events in ACS pts with
new onset and prior AF GRACE Registry
(Am J Cardiol 2003;92:1031–1036)
Survival of patients with NSTEMI and AF
PURSUIT – RCT
(Am J Cardiol 2001; 88: 76-9)
Type of ACS and 1-year outcome of
patients with new onset AF
(Am J Cardiol 2009;104:1317–23)
Multivariate predictors of new-onset AF in
ACS
GRACE registry
(Am J Cardiol 2003;92:1031–6)
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- Older age (per 10-year increase, OR 1.58 (1.49 to 1.67)
- Female gender OR 1.24 (1.07 to 1.45)
- STEMI OR 2.08 (1.74 to 2.49)
- NSTEMI OR 1.85 (1.55 to 2.22)
- HT OR 1.34 (1.17 to 1.53)
- HR per 30 beats/min increase, OR 1.65 (1.53 to 1.79)
- BP per 20 mm Hg decrease OR 1.16 (1.12 to 1.21)
- Cardiac arrest on presentation OR 1.65 (1.17 to 2.34)
- Killip class II or higher OR 1.36 (CI 1.17 to 1.57)
-Initial serum creatinine OR 1.07 (1.01 to 1.15)
RCTs – rate vs. rhythm control in AF
Study
Patients
Rate
Rhythm
End-points/
follow-up
Outcome
RACE
(NEJM 2002: 347;
1834-40)
522pts
Persistent AF <1 y
History AF
recurrence after of
at least 1 ECV
256 pts
Digitalis,
BBl, CCB,
comb, AVN
abl.+pace
+anticoag.
266 pts
ECV+sotalol/
flecainide/propafeno
ne/amiodarone
+ anticoagulation
(b.a. 4 weeks, aspirin)
CEP
CV death
HF
Thromboemb. events
Bleeding
Pacemaker
Adverse effects
24 mo
17.22% vs 22.6%
-5.4 (-11.0 to 0.4)
Women
10.5% vs 32%
-21.5 (-30.8 to -12.1)
HT – 17.3% vs 30.8%
-13.5 (-22.2 to -4.9)
SRm - 39% RhythmC
AFFIRM
(NEJM 2002: 347;
1825-33.)
4060 pts
With 1RF for
stroke or death
Recurrent AF
2027
Bbl, CCB,
digoxin,
comb
2033
ECV ,
amiodarone,
disopyramide,
flecainide,
moricizine,
procainamide,
propafenone,
quinidine, sotalol,
comb.
Primary – mortality
CEP- death, stroke,
bleeding, cardiac
arrest
5y
Death – adj HR 1.18
(0.99 to 1.41, p=0.07).
CHF. CAD, >65y ↑ risk
death with RhythmC
Adv.E: Pulm, Qtprol,
Tdp, brady ↑with
RhythmC
Hosp. 73% vs 80.1%,
p<0.001
STAF
(JACC 2003;
41:1690–6)
200 pts
High-risk AF
recurrence: AF>4
weeks and <2 years,
LAD>45mm,
LVEF<45%,
NYHA>II, >1 ECV
and AF recurrence
100
BBl,
digitalis,
CCB, AVN
abl/mod
with or w/o
PM
100
Primary - CEP: death,
stroke/ TIA, CPR,
syst.embolism
Sec. – bleeding, QoL,
echo, HR, SRm
3y
CEP- 5.54%/y vs 6.09%/y,
p=0.99
Hosp: 54 vs 24, p<0.001
SRm 23% vs 0%
No CAD, no LVD – ECV
+class 1 AAD/ sotalol
CAD or LVD –
ECV+amiodarone
Study
Pts
Rate
Rhythm
End-points/
follow-up
Outcome
PIAF
(Lancet 2000; 356:
1789–94)
252 pts
125
Diltiazem
127
ECV amiodarone
Primary: symptom impr
Secondary: HR, Srm, Ex.toler,
QoL, Hosp.
Follow-up: 1y
Symtpoms impr- NS
SRm -56% vs 10%,
p<0.001
Ex.toler. ↑ with
RhythmC
Hosp. 69%vs
24%,p=0.001
Adv. E 14%vs 25%,
p<0.05
Symptomatic,
persistent AF>7d
and <360d
HOT CAFE
(Chest 2004;
126:476–86)
205 pts
1st persistent AF
episode, required
ECV, duration >7 d
and <2 y
101 pts
24-h Holter
ECG BBl,
CCB, digoxin
or comb, ECV
and AVN abl.
with PM
104 pts
ECV stepwise AADs disopyramide,
propafenone, sotalol,
and amiodarone
Primary: CEP – death,
Thromboembolic ev. (ischemic
stroke) and major bleeding
Sec. EP: HRm, SRm, Ex. toler,
Hosp., proarrhythmia, CHF,
hemorrhage
Mean follow-up 1.7y
CEP: 1.98 (0.28 to
22.3).
Secondary: SRm –
63.5%
Hospit. 8 vs 32, p<0.05
Ex. toler., FS ↑ in
RhythmC
CAFÉ II
(Heart 2009: 95;
924-9
61 pts
HF and persistent
AF (mean 14m)
31pts
guidelines
30 pts
Guidelines
Amiodarone 3m prior
ECV and after, BBL
or digoxin
Symtpoms, NYHA, 6MWT,
QoL, LVF, NT-proBNP,
Follow-up 1y
NYHA, 6MWT – NS
LVF and QoL ↑ and
NT-proBNP ↓ with
Rhythm C
SRm – 66%, HRm90%
AF-CHF
(NEJM 2008; 357;
2667-77)
1376 pts
LVEF<35%, or
NYHA II-IV CHF,
parox or persist AF
694 pts
Bbl, digoxin,
AVNabl PM
682 pts
ECV, amiodarone,
sotalol, dofetilide
Primary: CV death
Secondary: any death, stroke,
HF worsen
CEP: CV death, stroke, HF
worsen
Follow-up 12 mo (up 74mo)
CV death
Adj HR1.05 (0.851.29)
Secondary and CEP NS
J-RHYTHM
(Circ J 2009: )
823 pts
Paroxysmal AF
404
Bbl, CCB,
digoxin
423
Guideline treatment
Primary: CEP- mortality,
cerebral infarct, bleed, hosp,,
HF, syst. emb, disability
Sec: QoL, effic, safety AADs
Follow-up 578d
Event free survival
RhythmC
HR 0.664 (0.481-0.917)
Rhythm C better in
>65y, male, HT, no
history CHF, ↑QoL
METAANALYSIS
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5 RCTS
AFFIRM, RACE, STAF, PIAF,
HOT-CAFÉ
5239 pts with persistent AF
or at high-risk for AF
recurrence
End-points:
all-cause mortality
Stroke
Rate C with antic. is
equivalent to RhythmC in
terms of all-cause mortality
and
ischemic
stroke,
RhythmC may be favorable
in selected patients
(De Denus et al Arch Intern
Med. 2005)
A)
B)
Odds ratios for all-cause mortality
Odds ratios for ischemic stroke
METAANALYSIS
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5 RCTS
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AFFIRM, RACE, STAF, PIAF, HOT-CAFÉ
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5239 pts with persistent AF or at highrisk for AF recurrence
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Follow-up: 1-3.5 years
•
End-points:
-
CEP – all cause
thromboembolic stroke
-
Major bleeding - NS
-
Systemic emboli – NS
•
death
and
Rate C strategy is associated with
significant reduction of CEP (all-cause
death and thromboembolic events) as
compared with RhythmC strategy,
especially in older population with
persistent AF or at high risk for AF
reoccurrence and longer follow-up
(Testa et al. Eur Heart J, 2005)
A) Odds Ratios for CEP Rate C vs RhythmC groups
B) Odds ratios for CEP in subgroups of pts≥65y
C) Odds ratios for CEP in subgroups of pts≥65y and >20mo
follow-up
Rate vs Rhythm control in pts with HF and AF
•
Meta-analysis – AF in CHF
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2425 pts in 3 RCT AFFIRM, RACE, AF-CHF
•
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Hospitalizations: due to AF and
bradyarrhythmias 9% vs 14%, p=0.001 and 3% vs
6%, p=0.02
(Caldeira et al. Eur J Int Med 2011: 22; 448–55.)
Meta-analysis 2012 updated
 8 RCTs- STAF, PIAF, HOT-CAFÉ, AFFIRM, RACE,
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CAFÉ II, CHF-AF, J-RHYTHM
7499 pts
Follow-up: 1-3.5 y
End-points: all-cause mortality, CV mortality,
arrhythmic/SCD mortality, ischemic stroke,
systemic embolism, major bleeding
No significant difference between both arms
RateC and RhythmC in all analyzed end-points
Subgroup analysis: RCTs >50% pts with HF
5 RCTs – STAF, AFFIRM, CAFÉ-II, CHF-AF, RACE
HOT-CAFÉ
 Systemic embolism : 0.43 [0.21—0.89] in
favor of Rate C strategy
RATE Control versus RHYTHM
Control in NSTEMI
- There are no clinical trials on comparison of rate
and rhythm control strategies in pts with ACS
- There are few retrospective analyses of rhythm
and rate control therapies in ACS
Beta-blockers and AF in ACS
CAPRICORN

1959 pts, 3-21 d post-MI with LVD
984 pts - placebo
975 pts – carvedilol
Outcome: atrial or ventricular
arrhythmias
Follow-up average 1.3 y
Any AF -22/975 (2.3%) vs 53/984
(5.4%)
HR 0.41 (0.2-0.68), p=0.0003
New AF 16/894 (1.8%) vs 31/895
(3.5%)
HR 0.51 (0.28-0.93), p=0.02

(JACC 2005: 45; 525-30)
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Survival free of atrial fibrillation
Rhythm Control in ACS STEMI- GUSTO
III study analysis
(Heart 2002;88:357–62.)
Unadjusted
Adjusted for
baseline
characteristics*
Adjusted for
baseline
characteristics
and pre-AF
complications**
Amiodarone
1.23 (0.81 to 1.87)
1.21 (0.77 to 1.90)
1.08 (0.68 to 1.74)
DCC
1.22 (0.75 to 2.01)
1.24 (0.73 to 2.10)
1.16 (0.66 to 2.03)
Amiodarone
1.12 (0.78 to 1.63)
1.14 (0.75 to 1.73)
1.03 (0.67 to 1.57)
DCC
1.24 (0.81 to 1.91)
1.33 (0.82 to 2.16)
1.27 (0.78 to 2.09)
30-day mortality
1-year mortality
*Adjusted for grouping of atrial fibrillation (AF) including paroxysmal AF, chronic AF, and no previous AF; pulse rate; systolic blood
pressure; age; history of myocardial infarction; angina; percutaneous transluminal coronary angioplasty; Killip class; and smoking class
(previous, current, never).
**In addition to the above demographics, adjusted for significant pre-AF complications including worsening heart failure, shock, acute
ventricular septal, defect, and stroke.
RHYTHM VS RATE CONTROL IN ACS STEMI and
LVD/HF VALIANT (Heart 2010: 96; 838-42.)
-Retrospective analysis
-1131 pts post-MI with LVD/HF
-760 pts Rate C – BBL 84.7%, digoxin
43.8%
-371 pts RhythmC – amiodarone
87.3% and other AADs 14.8%
-End-points: mortality and stroke
-0-45 days and 45-1096 days
-Stroke – NS
-Mortality 0-45d – 12.4% vs 6.1%
Adj HR 1.9 (1.2-3.0), p=0.004
-- Mortality 45-1096 d – 30.9% vs
29.0%
-Adj HR 1.1 (0.9-1.4), p>0.05
-95.7% of death in pts on
amiodarone
ESC Guidelines 2010 on the management of AF
ESC Guidelines 2010 on the management of AF
ESC AF GUIDELINES 2012 UPDATE
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Updates on RATE and RHYTHM CONTROL
Vernakalant – contraindication for patients
with ACS
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Dronedarone
Catheter ablation
CONCLUSIONS
 Current evidence for treatment of AF in ACS is based on retrospective
analyses of trials in patients with ACS
 Acute management of arrhythmia -ESC guideline recommendation special populations AF in ACS
 Treatment of underlying disease, ischemia and comorbidities
 Proper antithrombotic therapy
 Upstream therapy
 After stabilization choice of rate or rhythm control strategy should be
done as recommended for patients with CAD based on presence of
symptoms, special considerations, safety and efficacy of AADs, benefit
of each strategy
 There is a need for prospective clinical trials on rhythm and rate control
management of AF in patients with NSTEMI/ACS