thuốc chẹn beta trong suy tim

Burden of Heart Failure
•
•
•

Lifetime risk > 20% for Americans >40 years of age
870,000 new cases diagnosed annually

Prevalence in US: 5.7 million

1 5
in

of all

Americans
will be in the

over

Age 4 0
Lifetime risk = > 2 0 %

65

age bracket

by 2050

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HF is associated with
high mortality rates

PATIENTS DIE WITHIN
~50% OF
5 YEARS OF DIAGNOSIS
1

~1 IN

4

HF PATIENTS DIE WITHIN
1 YEAR OF DIAGNOSIS2

1. Roger et alCirc Res 2013; 113:646-59; 2. Levy et al. N Engl J Med 2002;347:1397–402

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ACC Focused update on HF, 2017

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The Beginning of the Beta Blocker Story
◼
◼

◼

◼
◼

1985, LDS Hospital, Jeffrey Anderson, et al
50 patients with IDC (EF<30%)
Randomized to metoprolol (12.5-50 mg bid)
versus placebo
Followed for 18 months
Results
Low dose beta blockade tolerated by 80% of
patients
◼ Death: metoprolol = 3, placebo = 8
◼ Significant improvement in functional class
◼

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Liệu pháp chẹn  trong suy tim: Tử vong do mọi nguyên nhân
US Carvedilol Program

Survival %

1.0

Carvedilol

Survival %
100

0.9

90

N=1094

Placebo

0.8

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70

Risk reduction=65%

Risk reduction=35%

p<0.001

Placebo

p=0.00014

60

0.6

Carvedilol

N=2289

80

0.7

COPERNICUS

50

0.5
0 50 100 150 200 250 300 350 400 days

0

4

8

12

16

20

24

28 months

.

Survival %
1.
0

Mortality %

CIBIS-II

20

Bisoprolol

N=2647
0.
8

Placebo

Risk reduction=34%

MERIT-HF
Placebo

N=3991

15

Metoprolol CR/XL

10

Risk reduction=34%

5

p<0.0001

p=0.0062

0.
6

0
0

200

400

600

800 days

0

3

6

9

12

15

18

21 months


CIBIS-II: bisoprolol (BB) significantly reduced
all-cause mortality in patients with HFrEF
Bisoprolol

CIBIS-II

1.0

Bisoprolol 1.25–10 mg*
QD vs placebo*

Number of patients

2,647

Average age (years)

61

Female (%)

20

LVEF
Primary outcome
Mean follow-up
(years)

≤35% (NYHA III–IV)

Probability of Survival

Intervention

Placebo

0.8

34% relative risk reduction
p<0.0001
0.6

All-cause mortality
0

1.3

0

200

400

600

800

Time after inclusion (days)

* On top of standard therapy with diuretics and ACEIs

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CIBIS-II Investigators. Lancet 1999;353:9–13


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Medical Therapy for Stage C HFrEF:
Magnitude of Benefit Demonstrated in RCTs

GDMT

RRReduction
inMortality

NNTforMortality
Reduction
(Standardizedto36mo)

RRReduction
inHF
Hospitalizations

ACEinhibitoror
ARB

17%

26

31%

Betablocker

34%

9

41%

Aldosterone
antagonist

30%

6

35%

Hydralazine/nitrat
e

43%

7

33%

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GWTG HF Achievement Measures

* Modified to include Beta Blocker at Discharge and Discharge Instructions rather than Evidence-Based Beta Blocker at D/C and Post Discharge Appointment
Baseline = Admissions Jan2005 – Dec2005
April 2013
Current = Overall

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Beta-Blockers: A practical view
• Not all are BB are created equal
1. Carvedilol
2. Metoprolol succinate ER
3. Bisoprolol

β1:β2
1:1 (plus α1)
30:1
130:1

Dosing
bid
daily/bid
daily

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Cost
$4/mo
more
?$4

Lợi điểm của chọn lọc trên thụ thể Beta 1

Opie L.H. Drugs for the Heart 8th, 2012.
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Beta-Agonism v. Antagonism:
CHRONIC

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Beta-Agonism v. Antagonism:
ACUTE

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Hạn chế tương tác với β2:
Chẹn Beta chọn lọc trên β1
CHẸN BETA
Không chọn lọc trên tim (β1, β2)
-ISA

Carvedilol*
Propranolol
Nadolol
Timolol
Sotalol

Tertalolol

Chọn lọc trên tim (β1)
-ISA

+ISA

Pindolol
Carteolol
Penbutolol
Alprenolol
Oxprenolol

Metoprolol
Atenolol
Esmolol
Bevantolol*
Bisoprolol
Betaxolol
Nebivolol#

+ISA

Acebutolol
Celiprolol

ISA: Intrinsic sympathomimetic activity (Hoạt tính giống giao cảm nội tại)
* : Có thêm đặc tính chẹn alpha yếu
#: có tính giãn mạch

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Reference: Cardiac Drug Therapy. 7

th edition

2007; Page 9


Tỷ lệ tử vong tăng theo tần số tim

Seccareccia F, et al. Am JPublic Health. 2001;91:1258
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Higher Beta Blocker
Dose Versus Lower
Heart Rate in Patients
with Heart Failure with
Reduced Ejection
Fraction

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Aim
• To compare the survival benefit of beta
blocker dose and heart rate on mortality in
patients with heart failure with reduced
ejection fraction (HFrEF)

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Study
Population
• Low Dose (daily):
– < 25 mg of carvedilol
– < 100 mg of metoprolol
succinate

• High Dose (daily):
– ≥ 25 mg of carvedilol
– ≥ 100 mg of metoprolol
succinate
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Resul
ts
• 114,010 heart failure patients
• 36,168 on low dose

• 77,842 on high dose
• Average follow up duration
3.3 years

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Hazard Ratios after Matching by
Quartile and Beta Blocker Dose
4.5
..3.9r42

4

I

1

=

•

3.5
3

2 1
.

2.6481

2.5

2.16

2

1.6

1.5
1

0.5
Quartile

1

• High

2

3

Dose

• Low Dose

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4