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The Importance of Beta-Blockers in Patients with Heart Failure:

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.

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The Importance of Beta-Blockers in Patients with Heart Failure:

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  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

  2. DECLARATION - 1 Declaration of Potential Conflict of Interest CRT • I have nothing to declare Aldo Block ACE-I / ARB Beta-Blockers

  3. BACKGROUND - 1 CHF - Proven Effective Therapies on All-Cause Mortality CRT ICD Aldo Block ACE-I / ARB Beta-Blockers

  4. BACKGROUND - 2 Resynchronization-defibrillation for Ambulatory heart Failure Trial (RAFT) • 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

  5. BACKGROUND - 3 RAFT Results: Death or CHF Hospitalization ICD HR = 0.75 95% CI: 0.64 – 0.87 p < 0.001 60 50 40 CRT-ICD Cumulative Incidence 30 20 10 0 5 0 1 2 3 4 6 Years of Follow-up Tang AS et al. N Engl J Med 363:2385-95, 2010

  6. BACKGROUND - 4 CHF - Proven Effective Therapies on All-Cause Mortality CRT ICD Aldo Block ACE-I / ARB Beta-Blockers

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

  8. 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. 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

  9. 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

  10. RESULTS - 2 Beta-Blocker Use Distributions 629 < 50% target ≥ 50% target p < 0.001 489 number 356 (34%) (39%) (67%)

  11. RESULTS - 3 Population Differences by Beta-Blocker Dosage

  12. RESULTS - 4 Death / CHF Hospitalization by Beta-Blocker Dosage HR = 1.50 95% CI = 1.24 – 1.81 p < 0.001 60 < 50% 50 40 Cumulative Incidence 30 ≥ 50% 20 10 0 5 0 1 2 3 4 6 Years of Follow-up

  13. RESULTS - 5 Independent Predictors of Primary Outcome

  14. RESULTS - 6 Death / CHF Hospitalization by Beta-Blocker Dosage by bisoprolol dosage (N=489) by beta-blocker dosage (N=1474) p < 0.0001 p < 0.0001 60 60 60 60 < 50% < 50% 40 Incidence 20 ≥ 50% ≥ 50% 40 40 40 0 5 0 1 2 3 4 6 by carvedilol dosage (N=629) by metoprolol dosage (N=356) p < 0.0001 p = 0.006 20 20 20 < 50% < 50% Incidence ≥ 50% ≥ 50% 0 0 0 5 5 5 0 0 0 1 1 1 2 2 2 3 3 3 4 4 4 6 6 6 Years of Follow-up Years of Follow-up

  15. RESULTS - 7 Death / CHF Hospitalization by RAFT Randomisation Randomised to CRT-ICD (N=740) Randomised to ICD (N=734) p < 0.001 p = 0.07 60 60 < 50% < 50% 40 40 Cumulative Incidence 20 20 ≥ 50% ≥ 50% 0 0 5 5 0 0 1 1 2 2 3 3 4 4 6 6 Years of Follow-up Years of Follow-up

  16. INFERENCES In this subgroup analysis of CHF patients studied in RAFT: • 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

  17. 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

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