A R esynchronizationDefibrillation for A mbulatory Heart F ailure T rial RAFT Analysis L Brent Mitchell Jean L Rouleau Gary E Newton Jonathon Howlett Elizabeth ID: 912494
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Slide1
The Importance of Beta-Blockers in Patients with Heart Failure:
A
R
esynchronization-Defibrillation for
A
mbulatory Heart
F
ailure
T
rial (
RAFT
) Analysis
.
L. Brent Mitchell, Jean L.
Rouleau
, Gary E. Newton, Jonathon
Howlett
, Elizabeth
Yetisir
, George A. Wells, Anthony S.L. Tang
Slide2DECLARATION - 1
Beta-Blockers
ACE-I / ARB
Aldo Block
CRT
Declaration of Potential Conflict of Interest
I have nothing to declare
Slide3BACKGROUND - 1
Beta-Blockers
ACE-I / ARB
Aldo Block
ICD
CRT
CHF - Proven Effective Therapies on All-Cause Mortality
Slide4multicenter, randomized, two parallel-group, clinical trial
1798 patients with NYHA II/III congestive heart failure
receiving optimal medical therapy
with LVEF ≤ 0.30 and QRSd
≥ 120ms (≥ 200ms if V-paced) and with an independent indication for an ICD
were randomized 1:1 to receive an ICD or a CRT-ICD
R
esynchronization-defibrillation for
A
mbulatory heart
F
ailure
T
rial (
RAFT
)
BACKGROUND - 2
Slide5RAFT
Results: Death or CHF Hospitalization
BACKGROUND - 3
0
10
20
40
50
30
Cumulative Incidence
1
2
3
4
6
0
Years of Follow-up
5
60
ICD
CRT-ICD
HR =
0.75
95
% CI: 0.64 –
0.87
p < 0.001
Tang AS et al. N
Engl
J Med 363:2385-95, 2010
Slide6BACKGROUND - 4
CHF - Proven Effective Therapies on All-Cause Mortality
Beta-Blockers
ACE-I / ARB
Aldo Block
ICD
CRT
Slide7PURPOSE
To assess the contemporary importance,
independence, and dose-dependence of
beta-blocker therapy in the congestiveheart failure patients studied in RAFT.
Slide8METHODS
PATIENT POPULATION: RAFT patients that were treated
with one of bisoprolol
, carvedilol, or metoprolol.BETA-BLOCKER TARGET DOSAGES: were as defined by
ESC guidelines1 - bisoprolol 10 mg/d,
carvedilol 50 mg/d,metoprolol 200 mg/d.
PRIMARY OUTCOME: death or CHF hospitalization.STATISTICS: Times to outcome displayed as KM curves.Sixteen variables were included in stepwise proportional
hazards analyses.
1. McMurray JJV et al.
Eur
Heart J 33:1787-847, 2012
Slide9RESULTS - 1
The RAFT Patient Population:
N = 1798, mean age 66 yrs, 83% male, 67% ischemic
80% NYHA Class II, mean LVEF 0.23 90% beta-blocker use, 97% ACE-I / ARB use
42% spironolactone use
This Substudy Patient Population (82%):
N = 1474, mean age 66 yrs, 83% male, 66% ischemic 82% NYHA Class II, mean LVEF 0.23
100% beta-blocker use, 97% ACE-I / ARB use
42%
spironolactone
use
Slide10RESULTS - 2
Beta-Blocker Use Distributions
< 50% target
≥ 50% target
number
489
356
629
(39%)
(34%)
(67%)
p < 0.001
Slide11Population Differences by Beta-Blocker Dosage
RESULTS - 3
VARIABLE
BB < 50%
Target
BB ≥ 50% Target
P-valueAge (years ± SD)
67.5 ± 9.0
64.6 ± 9.6
<0.0001
Ischemic
HD n(%)
541
(73.2%)
436
(59.3%)
<0.0001
NYHA
Class II n(%)
568 (76.9%)
621 (84.5%)
0.0002
Weight (kg ± SD)
79.6 ± 16.5
85.3 ± 18.1
<0.0001
BMI (± SD)
27.1 ± 5.1
28.6 ± 5.4
<0.0001
Prior CABG n(%)
288 (39.0%)
214 (29.1%)
<0.0001
PVD n(%)
88 (11.9%)
61 (8.3%)
0.0216
CHF Hosp
< 6mo n(%)
211 (28.6%)
166 (22.6%)
0.0087
Beta-blocker use at baseline n(%)
643 (87.0%)
709 (96.3%)
<0.0001
ASA use n(%)
517 (70.0%)
477 (64.9%)
0.0381
Warfarin use n(%)
231 (31.3%)
266 (36.2%)0.0452
Clopidogrel use n(%)
130 (17.6 %)96 (13.1%)
0.0158
Amiodarone use n(%)114 (15.4%)
78 (10.6%)
0.0060
eGFR (ml/min/1.73m2 ± SD)
58.7 ± 21.9
61.8 ± 19.10.00396 MWT distance (m ± SD)
346 ± 111
367
± 107
0.0010
Slide12Death
/
CHF Hospitalization by Beta-Blocker Dosage
RESULTS - 4
0
10
20
40
50
30
Cumulative Incidence
1
2
3
4
6
0
Years of Follow-up
5
60
< 50%
≥ 50%
HR =
1.50
95
%
CI = 1.24
–
1.81
p < 0.001
Slide13Independent Predictors of Primary Outcome
RESULTS - 5
PARAMETER
HR (95% CI)
P-value
previous
CABG1.63 (1.32-2.02)
<0.0001
beta-blocker < 50% target
1.50 (1.24-1.81)
<0.0001
ICD without CR
T
1.50 (1.25-1.80)
<0.0001
ischemic heart disease
1.39 (1.07-1.80)
0.01
peripheral
vascular disease
1.36 (1.04-1.76)
0.02
lower estimated GFR (per 5 units)
1.10 (1.01-1.16)
0.0002
Slide140
20
40
1
2
3
4
6
0
5
60
0
20
40
1
2
3
4
6
0
5
60
0
20
40
1
2
3
4
6
0
5
60
RESULTS - 6
Death
/
CHF Hospitalization by Beta-Blocker Dosage
Years of Follow-up
< 50%
≥ 50%
Incidence
0
20
40
1
2
3
4
6
0
5
60
Incidence
by beta-blocker dosage (N=1474)
Years of Follow-up
< 50%
< 50%
< 50%
≥ 50%
≥ 50%
≥ 50%
by
carvedilol
dosage (N=629)
by
bisoprolol
dosage (N=489)
by metoprolol dosage (N=356)
p < 0.0001
p < 0.0001
p < 0.0001
p = 0.006
Slide150
20
40
1
2
3
4
6
0
5
60
0
20
40
1
2
3
4
6
0
5
60
RESULTS - 7
Cumulative Incidence
Years of Follow-up
Death
/
CHF Hospitalization by RAFT Randomisation
Randomised to CRT-ICD
(N=740)
Years of Follow-up
p < 0.001
p = 0.07
Randomised to ICD (N=734)
< 50%
≥ 50%
< 50%
≥ 50%
Slide16independent predictors of death / CHF hospitalization were:
beta-blockers use at < 50% (not ≥ 50%) of target dosage
use of an ICD (not a CRT-ICD)
ischemic heart disease and previous CABGperipheral vascular disease or impaired renal function
with lower dosage these outcome were 50% more likely there were no efficacy differences among the beta-blockers
carvedilol is more often used at ≥ 50% of target dosages
the superiority of higher beta-blocker dosages are less evident in CRT-ICD patients than in ICD patients
INFERENCES
In this subgroup analysis of CHF patients studied in RAFT:
Slide17The Importance of Beta-Blockers in Patients with Heart Failure:
A Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) Analysis
.
L. Brent Mitchell, Jean L.
Rouleau
, Gary E. Newton, Jonathon
Howlett
, Elizabeth
Yetisir
, George A. Wells, Anthony S.L. Tang