Effects on Outcomes of Heart Rate Reduction

by Ivabradine in Patients With Congestive Heart Failure:

Is There an Influence of Beta-Blocker Dose?

Effects on Outcomes of Heart Rate Reduction

by Ivabradine in Patients With Congestive Heart Failure:

Is There an Influence of Beta-Blocker Dose?

SSystolic ystolic HHeart failure treatment eart failure treatment

withwith

the the IIff inhibitor ivabradine inhibitor ivabradine TTrialrial

Clinical Clinical characteristicscharacteristics of patients of patients by by ββ-blocker status-blocker status

No BB BB <25% of target

dose

BB 25% to <50% of target

dose

BB

50% to <100% of target dose

BB

≥100% of target dose

Age, years 64 61 60 60 58

Resting HR, bpm 84.2 80.6 79.5 79.1 78.9

Systolic BP, mm Hg 121 117 120 122 125

LV EF, % 28.7 28.1 28.9 29.4 29.3

NYHA III or IV, % 58 54 49 50 51

COPD, % 33 11 11 9 5

Asthma, % 11 2 2 2 2

PAD, % 10 6 6 6 5

Hypertension, % 63 55 63 70 73

ACE/ARB, % 90 86 90 92 93

Diuretic, % 86 87 83 83 81

Swedberg K, et al. J Am Coll Cardiol 2012;59:1938-1945.

BB category

(% of target dose)

Placebo event rate (%)

Hazard ratio

95 % CI

PEP (CV death, HF hospitalisation) No β-blocker 39.3 0.71 0.55-0.93BB, 25% 40 0.74 0.59-0.92BB, 25% to <50% 30.8 0.81 0.68-0.98BB, 50% to <100% 24.8 0.88 0.72-1.07BB, ≥100% 20.1 0.99 0.79-1.24

HF hospitalisation

No β-blocker 29 0.62 0.45-0.85BB, 25% 29 0.68 0.52-0.89BB, 25% to <50% 22 0.74 0.59-0.93BB, 50% to <100% 18 0.83 0.65-1.05

BB, ≥100% 14 0.84 0.63-1.11**adjusted for interaction between baseline HR and randomised treatment

P

heterogeneity

0.35 

0.55

P

Trend

P

Trend adj**

0.056  0.135

0.12 0.19

Effect of ivabradine on outcomesEffect of ivabradine on outcomes by by ββ-blocker doses-blocker doses

Swedberg K, et al. J Am Coll Cardiol 2012;59:1938-1945.

<72

72 to <75

75 to <80

80 to <87

≥87

No BB BB<25% BB ≥100%

β-blocker category

Baseline HR category (bpm)

HR reduction according toHR reduction according toββ-blocker and HR category-blocker and HR category

HR reduction (bpm) from baseline to 28 days with ivabradine*

BB 25-50% BB 50-100%

*Placebo corrected

No impact of BB dose on HR reduction with ivabradine

Impact of baseline HR on HR reduction

with ivabradine

Swedberg K, et al. J Am Coll Cardiol 2012;59:1938-1945.

• In patients with systolic HF treated with guideline-recommended therapies, resting HR remains an important modifiable risk factor in patients treated with β-blockers

• When HR≥70 bpm, reduction of heart rate with ivabradine will provide additional clinical benefits regardless of the -blocker dose

• The magnitude of HR reduction with ivabradine, beyond that achieved by β-blockers, primarily determines subsequent outcome

CConclusiononclusion

Swedberg K, et al. J Am Coll Cardiol 2012;59:1938-1945.