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ефекти атенолола и метопролола на преживьаване - doiSerbia

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BIBLID: 0370-8179, 133(2005) 5-6 p. 242-247
UDC: 616.12-008.46-085
ЧѬЧќлЬѳлЧЦѯѿѯѿѳЬѸЧлѯѱѭѯѿѯѿѳЦѳѱѭЧбЬїъѳїѳхЧ
ѻѯѿЧяЦЬќѳяѳѻѿѳєѯѸЬдѸЧѭЧЦѯлЧѽќѯѸѨѭѯЦЬгЦѯѸ
ЬЦядѬЬйЬфЧЦйЬфѯѸѭѳЭѳяѭйѳќѯѸѱѳѭѳлЬїЦѳялдЭЬфѳ
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ƪǒǚǢǣǞǢǤǟǚǧǚǣǧǠǖǑǒǗǙǠǒǙǚǢǑǟǑǥǙǢǠǜǚǒǠǝǟǚǩǜǠǝǗǩǗǻǗǙǒǠǔǜǑǢǖǚǠǓǑǣǜǥǝǑǢǟǚǧǢǑǙǝǠǔǑǡǠǜǑǙǑǤǗǺǹǗǡǢǗǘǚǓǺǑ
ǓǑǻǑǒǠǝǗǣǟǚǜǑǣǧǢǠǟǚǩǟǠǞǚǟǣǥǦǚǨǚǹǗǟǨǚǹǠǞǢǑǖǑǣǢǨǑǚǠǙǟǑǩǑǓǑǣǗǜǑǠǜǠǞǒǚǟǠǓǑǟǚǖǠǔǑdzǑǹƹǚǺǠǓǗǣǤǥǖǚǹǗǹǗǒǚǠ
ǖǑǣǗǜǠǖǒǠǝǗǣǟǚǜǑǣǧǢǠǟǚǩǟǠǞǚǟǣǥǦǚǨǚǹǗǟǨǚǹǠǞǢǑǖǑǣǢǨǑǚǣǡǚǤǑǗǦǗǜǑǤǞǗǤǠǡǢǠǝǠǝǑǚǑǤǗǟǠǝǠǝǑǟǑǜǠǞǒǚǟǠǓǑǟǚǖǠ
ǔǑdzǑǹƴǤǥǖǚǹǑǹǗǒǚǝǑǜǠǞǡǑǢǑǤǚǓǟǑǡǢǠǣǡǗǜǤǚǓǟǑǚǢǑǟǖǠǞǚǙǚǢǑǟǑƭǢǚǤǗǢǚǹǥǞǚǙǑǥǜǺǥǩǚǓǑǻǗǥǣǤǥǖǚǹǥǣǥǒǚǝǚǣǤǑǢǠǣǤ
ǠǖǔǠǖǚǟǑǚǞǑǻǑNYHAǜǝǑǣǑII i IIIǗǹǗǜǨǚǠǟǑǦǢǑǜǨǚǹǑǝǗǓǗǜǠǞǠǢǗȎƴǤǠǡǗǖǗǣǗǤǒǠǝǗǣǟǚǜǑǜǠǹǚǣǥǝǗǩǗǟǚǚǟǧǚ
ǒǚǤǠǢǠǞǑǟǔǚǠǤǗǟǙǚǟǜǠǟǓǗǢǤǥǹǥǼǗǔǗǟǙǚǞǑǚǖǚǥǢǗǤǚǜǠǞǡǠǖǗǺǗǟǚǣǥǥǤǢǚǒǢǠǹǟǠǹǗǖǟǑǜǗǤǗǢǑǡǚǹǣǜǗǔǢǥǡǗǚǣǡǚǤǑǟǚǨǚ
ǜǠǖǜǠǹǚǧǹǗǡǢǚǞǗǻǚǓǑǟǑǤǗǟǠǝǠǝDǑǤǗǟǠǝǠǝǔǢǥǡǑE
ǚǣǡǚǤǑǟǚǨǚǜǠǖǜǠǹǚǧǹǗǡǢǚǞǗǻǚǓǑǟǞǗǤǠǡǢǠǝǠǝDǞǗǤǠǡǢǠǝǠǝǔǢǥ
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ǨǚƳǗǙǥǝǤǑǤǚǣǥǑǟǑǝǚǙǚǢǑǟǚǣǤǑǤǚǣǤǚǩǜǚǞǡǢǠǔǢǑǞǠǞSPSS 10.0ƭǥǞǥǝǑǤǚǓǟǠǡǢǗǘǚǓǺǑǓǑǻǗǒǠǝǗǣǟǚǜǑǝǗǩǗǟǚǧǞǗǤǠǡǢǠ
ǝǠǝǠǞ
ǚǑǤǗǟǠǝǠǝǠǞ
ǒǚǝǠǹǗǓǗǼǗǥǠǖǟǠǣǥǟǑǡǢǗǘǚǓǺǑǓǑǻǗǒǠǝǗǣǟǚǜǑǜǠǟǤǢǠǝǟǗǔǢǥǡǗ
ƲǢǗǘǚǓǺǑǓǑǻǗ
ǒǠǝǗǣǟǚǜǑǝǗǩǗǟǚǧǞǗǤǠǡǢǠǝǠǝǠǞǒǚǝǠǹǗǓǗǼǗǥǚǠǖǟǠǣǥǟǑǡǢǗǘǚǓǺǑǓǑǻǗǒǠǝǗǣǟǚǜǑǝǗǩǗǟǚǧǑǤǗǟǠǝǠǝǠǞƯǗǤǠǡǢǠǝǠǝ
ǹǗǙǟǑǩǑǹǟǚǹǗǣǞǑǻǚǠǢǗǝǑǤǚǓǟǚǢǚǙǚǜǙǑǟǑǣǤǑǟǑǜǜǠǞǒǚǟǠǓǑǟǠǔǖǠǔǑdzǑǹǑ
ǥǠǖǟǠǣǥǟǑǑǤǗǟǠǝǠǝ
ƳǗǙǥǝǤǑǤǚǣǤǥǖǚ
ǹǗǣǥǡǠǜǑǙǑǝǚǖǑǞǗǤǠǡǢǠǝǠǝǚǑǤǗǟǠǝǠǝǚǞǑǹǥǡǠǓǠǺǑǟǗǦǗǜǑǤǟǑǡǢǗǘǚǓǺǑǓǑǻǗǒǠǝǗǣǟǚǜǑǣǧǢǠǟǚǩǟǠǞǚǟǣǥǦǚǨǚǹǗǟǨǚ
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TABELA 1.ƭǝǚǟǚǩǜǑǠǒǗǝǗǘǹǑǒǠǝǗǣǟǚǜǑǣǑǒǝǑǔǠǞǚǥǞǗǢǗǟǠǤǗǪǜǠǞǧǢǠǟǚǩǟǠǞǚǟǣǥǦǚǨǚǹǗǟǨǚǹǠǞǢǑǖǑǣǢǨǑ
TABLE 1. Baseline characteristics of patiens with mild-to-moderate heart failure.
ƤǑǢǚǹǑǒǝǑ
Variable
ƴǤǑǢǠǣǤǡǢǠǣǗǩǟǠǔǠǖǚǟǗ
Age (average, years)
ƯǥǪǜǑǢǨǚǒǢǠǹ
Male (number)
ƸǚǡǗǢǤǗǟǙǚǹǑǒǢǠǹ
Hypertension (number)
ƧǚǹǑǒǗǤǗǣǞǗǝǚǤǥǣǒǢǠǹ
Diabetes mellitus (number)
HRǡǢǠǣǗǩǟǠǥǖǑǢǑǞǚǟǥǤ
HR (average, beats/minute)
SBPǡǢǠǣǗǩǟǠmm Hg
SBP (mean, mm Hg)
ISHCMǒǢǠǹ
ISHCM (number)
IDCMǒǢǠǹ
IDCM (number)
NYHAǜǝǑǣǑIIǒǢǠǹ
NYHA class II (number)
NYHAǜǝǑǣǑIIIǒǢǠǹ
NYHA class III (number)
ƨƷƮƭǡǢǠǣǗǩǟǠ
EF-LV (average)
ƣǢǠǹ
Number
(n=150)
pǢǑǙǝǚǜǗǚǙǞǗdzǥǤǗǢǑǡǚǹǣǜǚǧǔǢǥǡǑ
p (differences between treatment groups)
ƢǡǢǗǞǑƭ
A vs. C
ƯǡǢǗǞǑƭ
M vs. C
ƢǡǢǗǞǑƯ
A vs. M
j
j
j
p=ǣǤǑǤǚǣǤǚǩǜǑǙǟǑǩǑǹǟǠǣǤǡǢǠǨǗǟǤǟǚǚǟǤǗǢǓǑǝǡǠǓǗǢǗǻǑ
Ƣ=ǑǤǗǟǠǝǠǝǔǢǥǡǑƭ=ǜǠǟǤǢǠǝǟǑǔǢǥǡǑƯ=ǞǗǤǠǡǢǠǝǠǝǔǢǥǡǑHR=ǦǢǗ
ǜǓǗǟǨǚǹǑǢǑǖǑǣǢǨǑSBP=ǣǚǣǤǠǝǟǚǜǢǓǟǚǡǢǚǤǚǣǑǜISHCM=ǚǣǧǗǞǚǹǣǜǑǜǑǢǖǚǠǞǚǠǡǑǤǚǹǑIDCM=ǚǖǚǠǡǑǤǣǜǑǖǚǝǑǤǑǨǚǠǟǑǜǑǢǖǚǠǞǚǠǡǑ
ǤǚǹǑNYHAǜǝǑǣǑ=ǦǥǟǜǨǚǠǟǑǝǟǑǜǝǑǣǑǡǢǗǞǑNew York Heart AssociationƨƷƮƭ=ǗǹǗǜǨǚǠǟǑǦǢǑǜǨǚǹǑǝǗǓǗǜǠǞǠǢǗ
p – statistical significance (95% confidence interval); A – atenolol group; C – control group; M – metoprolol group; HR – heart rate; SBP – systolic
blood pressure; ISHCM – ishemic cardiomyopathy; IDCM – idiopathic dilated cardiomyopathy; NYHA class – New York Heat Association functional
class; EF-LV – left ventricular ejection fraction
ƴƳƲƴƭƫƢƳƸƫƤƪƢƹƨƮƱƭƶƲưƱƮƨƭƢƳƴƵƤƱ
TABELA 2.ưǗǘǗǺǗǟǑǜǝǚǟǚǩǜǑǖǠǔǑdzǑǻǑǜǠǖǒǠǝǗǣǟǚǜǑǣǑǒǝǑǔǠǞǚǥǞǗǢǗǟǠǤǗǪǜǠǞǚǟǣǥǦǚǨǚǹǗǟǨǚǹǠǞǢǑǖǑǣǢǨǑ
TABLE 2. Adverse clinical outcomes in patients with mild-to-moderate heart failure.
ƵǗǢǑǡǚǹǣǜǑǔǢǥǡǑ
Treatment group
Atenolol
Atenolol
ƯǗǤǠǡǢǠǝǠǝ
Metoprolol
ƭǠǟǤǢǠǝǟǑ
Control
ƶǜǥǡǟǠ
Total
ƪǟǑǩǑǹǟǠǣǤǑǟǑǝǚǙǑǓǑǢǚǹǑǟǣǗǚǙǞǗdzǥǔǢǥǡǑ
Significance (analysis of variance between groups)
ƣǢǠǹ
ǒǠǝǗǣǟǚǜǑ
Number of
patients
ƴǞǢǤ
ǣǓǚǥǙǢǠǨǚ
Death
(all causes)
ƣǠǝǟǚǩǜǠǝǗǩǗǻǗ
ǜǑǢǖǚǠǓǑǣǜǥǝǑǢǟǚǢǑǙǝǠǙǚ
Hospitalization
(cardiovascular reasons)
ƭǠǞǒǚǟǠǓǑǟǚ
ǖǠǔǑdzǑǹ
Combined
end-point
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cita stimulacijom βÑÿœÒœ¿²¨´»¨ª¿œ®œÉÊοѦ¨
efekti izazivaju signale remodelovawa i nastanak
1.20
Metoprolol grupa
Metoprolol group
Kumulativno preǘivqavawe
Cumulative survival
1.00
Atenolol grupa
Atenolol group
0.80
Kontrolna grupa
Control group
0.60
0.40
0.20
0.00
1
2
3
4
5
6
7
8
9
10
11
12
Meseci
Months
GRAFIKON 1.ƭǑǡǝǑǟƯǗǹǗǢǠǓǑǑǟǑǝǚǙǑǜǥǞǥǝǑǤǚǓǟǠǡǢǗǘǚǓǺǑǓǑǻǗǒǠǝǗǣǟǚǜǑǠǖǡǠǩǗǤǜǑǣǤǥǖǚǹǗǥǠǖǟǠǣǥǟǑǜǠǞǒǚǟǠǓǑǟǚǖǠǔǑdzǑǹǥ
ǑǤǗǟǠǝǠǝǞǗǤǠǡǢǠǝǠǝǚǜǠǟǤǢǠǝǟǠǹǔǢǥǡǚ
GRAPH 1. Kaplan-Meier analysis: cumulative survival from study enrollment until combined end-point or censorship is depicted for atenolol, metoprolol and control group.
ƴƳƲƴƭƫƢƳƸƫƤƪƢƹƨƮƱƭƶƲưƱƮƨƭƢƳƴƵƤƱ
TABELA 3.ƲǠǢǗdzǗǻǗǣǤǠǡǗǡǢǗǘǚǓǺǑǓǑǻǑǜǠǖǚǣǡǚǤǑǟǚǜǑǤǗǢǑǡǚǹǣǜǚǧǔǢǥǡǑǡǢǚǞǗǟǠǞƤǚǝǜǠǜǣǠǟǠǓǗǣǤǑǤǚǣǤǚǜǗ
TABLE 3. Comparison of survival experience between therapy groups using the Wilcoxon statistics.
ƵǗǢǑǡǚǹǣǜǑǔǢǥǡǑ
Treatment group
ƭǠǞǒǚǟǠǓǑǟǚ
ǖǠǔǑdzǑǹ
Combined
end-point
ƹǗǟǙǠǢǚǣǑǟǒǢǠǹ
Censored number
ƹǗǟǙǠǢǚǣǑǟ
ǡǢǠǨǗǟǑǤ
Censored
percentage
ƴǢǗǖǻǚǢǗǙǥǝǤǑǤ
Mean score
df
df
df
ƣǢǠǹǒǠǝǗǣǟǚǜǑ
ǣƸƫƴ
Number of patients
with HF
ƢǤǗǟǠǝǠǝǔǢǥǡǑ
Atenolol group
ƯǗǤǠǡǢǠǝǠǝǔǢǥǡǑ
Metoprolol group
ƴǤǑǤǚǣǤǚǜǑǡǠǢǗdzǗǻǗǞǡǑǢǠǓǑ
Pairwise comparison statistics
ƢǤǗǟǠǝǠǝǔǢǥǡǑ
Atenolol group
ƭǠǟǤǢǠǝǟǑǔǢǥǡǑ
Control group
ƴǤǑǤǚǣǤǚǜǑǡǠǢǗdzǗǻǗǞǡǑǢǠǓǑ
Pairwise comparison statistics
ƯǗǤǠǡǢǠǝǠǝǔǢǥǡǑ
Metoprolol group
ƭǠǟǤǢǠǝǟǑǔǢǥǡǑ
Control group
ƴǤǑǤǚǣǤǚǜǑǡǠǢǗdzǗǻǗǞǡǑǢǠǓǑ
Pairwise comparison statistics
p
p
p
Ƹƫƴ=ǧǢǠǟǚǩǟǑǚǟǣǥǦǚǨǚǹǗǟǨǚǹǑǢǑǖǑǣǢǨǑHF – chronic heart failure
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ƴƳƲƴƭƫƢƳƸƫƤƪƢƹƨƮƱƭƶƲưƱƮƨƭƢƳƴƵƤƱ
METOPROLOL AND ATENOLOL IN MILD-TO-MODERATE CHRONIC HEART FAILURE:
THE COMPARISON OF SURVIVAL BENEFIT
Vera ĆELIĆ, Biljana PENČIĆ, Milica DEKLEVA, Siniša DIMKOVIĆ, Maksimilijan KOCIJANČIĆ
Clinical Medical Centre “Dr. Dragiša Mišović” – Dedinje, Belgrade
ABSTRACT
The clinical end-point of all causes of mortality and cardiovascular hospitalisation (combined end-points) is a widely
accepted indicator of heart failure survival. The primary aim of
this study was to examine the effects of metoprolol and atenolol on combined end-points in patients with mild-to-moderate
heart failure. This study was designed to be comparative, prospective, and random. The criteria for study inclusion were: age
of 70 years or less, New York Heart Association (NYHA) Functional Class II and III, and an ejection fraction of the left ventricle of 40% or less. The patients (a total of 150) on therapy with
angiotensin-converting enzyme inhibitor and a diuretic were
randomised into three numerically equal therapy groups: 1) an
atenolol group; 2) a metoprolol group; and 3) a control group
(without beta-blockers). The follow-up period was 12 months.
The results were analysed using: the hi-square test, variance
analyses, Kaplan-Meier’s model, Wilcox’s statistics, and Cox’s
model. The cumulative survival rate for patients treated with
metoprolol was 88%, 78% for patients treated with atenolol,
and 48% for patients from the control group. It is clear that the
cumulative survival rate for patients treated with metoprolol
and atenolol is significantly higher compared to patients from
the control group. In addition, the survival rate of patients treated with metoprolol was considerably higher compared to the
survival rate of patients treated with atenolol. Metoprolol has
significantly reduced the relative risk of combined end-points
(71%) compared to atenolol (53%). The results of this comparative study clearly indicate that metoprolol and atenolol have
a favourable effect on the survival rate of patients with chronic heart failure. In addition, metoprolol is considerably more
effective than atenolol.
Key words: heart failure; beta-blockers; metoprolol; atenolol;
cumulative survival
Vera ĆELIĆ
Klinika za internu medicinu
Kliničko-bolnički centar „Dr Dragiša Mišović” – Dedinje
Heroja Milana Tepića 1, 11000 Beograd
Tel: 011 266 7122
E-mail: celgoran@eunet.yu
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