The Importance of Beta-Blockers in Patients with Heart Failure: A - - PowerPoint PPT Presentation

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The 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,

SLIDE 1

The 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

SLIDE 2

DECLARATION

Beta-Blockers ACE-I / ARB Aldo Block CRT Declaration of Potential Conflict of Interest

I have nothing to declare

SLIDE 3

BACKGROUND - 1

Beta-Blockers ACE-I / ARB Aldo Block ICD CRT CHF - Proven Effective Therapies on All-Cause Mortality

SLIDE 4

multicenter, 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

Resynchronization-defibrillation for Ambulatory heart Failure Trial (RAFT)

BACKGROUND - 2

SLIDE 5

RAFT Results: Death or CHF Hospitalization

BACKGROUND - 3

10 20 40 50 30

Cumulative Incidence

1 2 3 4 6

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

SLIDE 6

BACKGROUND - 4

CHF - Proven Effective Therapies on All-Cause Mortality Beta-Blockers ACE-I / ARB Aldo Block ICD CRT

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PURPOSE

To assess the contemporary importance, independence, and dose-dependence of beta-blocker therapy in the congestive heart failure patients studied in RAFT.

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METHODS

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 (dicotomized < 50% versus ≥ 50%). 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

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RESULTS - 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

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RESULTS - 2

Beta-Blocker Use Distributions

< 50% target ≥ 50% target

bisoprolol carvedilol metoprolol 100 200 300 400 500 600 700

number 489 356 629 (39%) (34%) (67%) p < 0.001

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Population Differences by Beta-Blocker Dosage

RESULTS - 3

VARIABLE BB < 50% Target BB ≥ 50% Target P-value Age (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 ± 19.1 0.0039 6 MWT distance (m ± SD) 346 ± 111 367 ± 107 0.0010

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Death / CHF Hospitalization by Beta-Blocker Dosage

RESULTS - 4

10 20 40 50 30

Cumulative Incidence

1 2 3 4 6

Years of Follow-up

5 60

< 50% ≥ 50% HR = 1.50 95% CI = 1.24 – 1.81 p < 0.001

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Independent Predictors of Primary Outcome

RESULTS - 5

PARAMETER HR (95% CI) P-value previous CABG 1.63 (1.32-2.02) <0.0001 beta-blocker < 50% target 1.50 (1.24-1.81) <0.0001 ICD without CRT 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

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20 40 1 2 3 4 6 5 60 20 40 1 2 3 4 6 5 60 20 40 1 2 3 4 6 5 60

RESULTS - 6

Death / CHF Hospitalization by Beta-Blocker Dosage

Years of Follow-up

< 50% ≥ 50%

Incidence

20 40 1 2 3 4 6 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

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20 40 1 2 3 4 6 5 60 20 40 1 2 3 4 6 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%

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independent 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 CABG
peripheral 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:

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The 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