COLA II研究，2004长城会演讲幻灯
Is Reluctance to Prescribe Carvedilol in the Elderly Justified? The COLA II Study
Henry Krum
NHMRC Centre of Clinical Research Excellence in Therapeutics, Monash University
Melbourne, Australia
Komajda M et al. Eur Heart J 2003
Utilisation of ?-Blockade for CHF in Clinical Practice
33
21
21
17
62
37
36
87
0%
50%
100%
Diuretics
ACE Inhibitors
β-blockers
Digoxin
Nitrates
Calcium antagonists
Spironolactone
ACEi, βB, diuretics
BRING UP Reasons for Not Commencing β-Blockade
Maggioni A et al. Heart 2003
Age of Patients in Major β-Blocker CHF Clinical Trials
5.4
12.5
20.8
1.2
2.0
3.1
0%
10%
20%
60-69 yrs
70-79 yrs
80+ yrs
Newly diagnosed CHF
Previously diagnosed CHF
Krum et al. Med J Aust 2001
CASE Study Patients with Heart Failure (Total n = 22,060)
Effect of β-Blocker vs Placebo on Mortality Non-Elderly Subjects
Study
% Weight
Risk ratio (95% CI)
0.57 (0.41 - 0.80)
13.2
0.35 (0.14 - 0.88)
2.3
0.66 (0.53 - 0.82)
27.9
0.61 (0.47 - 0.80)
20.6
0.91 (0.78 - 1.07)
COPERNICUS
CIBIS II
MERIT-HF
BEST
35.9
Overall (95% CI)
Risk ratio
0.72 (0.65 - 0.80)
Carvedilol U.S. Trials
Effect of β-Blocker vs Placebo on Mortality Elderly Subjects
0.75 (0.58 - 0.98)
21.2
0.45 (0.24 - 0.86)
4.9
0.70 (0.49 - 0.99)
12.3
0.70 (0.52 - 0.95)
17.6
0.91 (0.78 - 1.05)
44.0
0.79 (0.71 - 0.89)
COPERNICUS
Carvedilol U.S. Trials
CIBIS II
MERIT-HF
BEST
Overall (95% CI)
Study
% Weight
Risk ratio (95% CI)
Risk ratio
SENIORS All Cause Mortality or CV Hospital Admission
No. of events: Nebivolol 332 (31.1%); Placebo 375 (35.3%)
Event free
Survival %
HR 0.86 [0.74;0.99] , p = 0.039
50
60
70
80
90
100
0
6
12
18
24
30
36
Time (months)
Nebivolol
Placebo
Hazard ratio and 95% CI
Death or CV Hospitalisation by Subgroup
Favours
Nebivolol
Placebo
Nebivolol
Favours
Placebo
0.50
0.60
0.70
0.80
0.90
1.00
1.10
1.20
BRING UP Independent Predictors of ? Blockers Tolerability
Maggioni A et al. Heart 2003
COLA II Background
Continued under-utilisation of beta-blockers for systolic HF in everyday practice, despite overwhelming data supporting their efficacy
Advanced age is a common reason for non-prescribing of beta-blockers (BRING-UP)
Concerns re poor tolerability may be a major factor in the under-utilisation of these agents in this setting
Specific assessment of tolerability of beta-blockers in elderly CHF cohort has not as yet been performed
COLA II Study Aims
To determine tolerability of carvedilol introduction in elderly systolic CHF patients in everyday clinical practice
To determine whether there are differences in tolerability (and efficacy) in elderly CHF patients sub-grouped according to age
COLA II Study Design
1000+ CHF patients >70 years old receiving carvedilol
Multinational, recruitment May 02 – Aug 03
“Real-world” setting:
General physicians
Primary care practitioners
Non-teaching hospital cardiologists
Geriatricians
Prospective (6-month) observational assessment of tolerability according to age:
≥70<75; >75-80; >80 years
COLA II Definition of Tolerability
Over 6 months of the study period:
Patients had received ≥3 months carvedilol therapy
End dose: ≥6.25 mg bid carvedilol
COLA II Evaluations Performed
Key baseline demographic variables
Effect of carvedilol on SBP, DBP, HR, LVEF, NYHA according to age
Tolerability of carvedilol
Impact of co-morbidity on tolerability of carvedilol
Dose of carvedilol achieved according to age
COLA II Recruitment
RUSSIA
(n=28)
CHINA
(n=52)
AUSTRALIA
(n=98)
NETHERLANDS
AUSTRIA
HUNGARY
GREECE
(n=731)
COLOMBIA
ARGENTINA
(n= 100)
COLA II Baseline Demographics According to Age
71.7
76.4
77.4?
ACEi (%)
?
?
?
?
13.9
13.2?
ARB (%)
?
?
?
58.6
60
60.4
Ischaemic heart disease (%)
?
?
?
?
26.3*
29.2
32.3
Diabetes (%)
?
?
?
?
38.0
38.5
36.9
LVEF (%)
?
?
?
?
6
6
3
IV (%)
43
47
47
III (%)
44
44
45
II (%)
6
4
4
NYHA Class I (%)
?
?
?
?
41.4**
56.1
60.4
Gender (% Male)
?
?
?
>80
Years
(n=297)
75 - 79 years
(n=310)
≥70<75 years
(n=402)
12.5
?
?
?
?
22.6
25.4?
Spironolactone (%)
21.0
?
?
?
?
63.5
68.2?
Diuretics (%)
67.3
26.8
32.6?
Digoxin (%)
25.9
?
?
?
?
42.4
41.9
42.8
Hospitalised last 6 mths (%)
?
?
?
?
*P<0.05, **P<0.001 by ANOVA
COLA II Baseline Demographics According to Age
71.7
76.4
77.4?
ACEi (%)
?
?
?
?
13.9
13.2?
ARB (%)
?
?
?
58.6
60
60.4
Ischaemic heart disease (%)
?
?
?
?
26.3*
29.2
32.3
Diabetes (%)
?
?
?
?
38.0
38.5
36.9
LVEF (%)
?
?
?
?
6
6
3
IV (%)
43
47
47
III (%)
44
44
45
II (%)
6
4
4
NYHA Class I (%)
?
?
?
?
41.4**
56.1
60.4
Gender (% Male)
?
?
?
>80
Years
(n=297)
75 - 79 years
(n=310)
≥70<75 years
(n=402)
12.5
?
?
?
?
22.6
25.4?
Spironolactone (%)
21.0
?
?
?
?
63.5
68.2?
Diuretics (%)
67.3
26.8
32.6?
Digoxin (%)
25.9
?
?
?
?
42.4
41.9
42.8
Hospitalised last 6 mths (%)
?
?
?
?
*P<0.05, **P<0.001 by ANOVA
COLA II Baseline Demographics According to Age
71.7
76.4
77.4?
ACEi (%)
?
?
?
?
13.9
13.2?
ARB (%)
?
?
?
58.6
60
60.4
Ischaemic heart disease (%)
?
?
?
?
26.3*
29.2
32.3
Diabetes (%)
?
?
?
?
38.0
38.5
36.9
LVEF (%)
?
?
?
?
6
6
3
IV (%)
43
47
47
III (%)
44
44
45
II (%)
6
4
4
NYHA Class I (%)
?
?
?
?
41.4**
56.1
60.4
Gender (% Male)
?
?
?
>80
Years
(n=297)
75 - 79 years
(n=310)
≥70<75 years
(n=402)
12.5
?
?
?
?
22.6
25.4?
Spironolactone (%)
21.0
?
?
?
?
63.5
68.2?
Diuretics (%)
67.3
26.8
32.6?
Digoxin (%)
25.9
?
?
?
?
42.4
41.9
42.8
Hospitalised last 6 mths (%)
?
?
?
?
*P<0.05, **P<0.001 by ANOVA
COLA II Change in SBP according to Age
136.6
139.7
137.6
126.6
124.0
125.4
0
40
80
120
160
>70 <75 years
(n=380)
75-79 years
(n=278)
> 80 years
(n=265)
Baseline
6 months
? = -10.0 mmHg*
? = -15.7 mmHg*
? = -12.4 mmHg*
*P<0.05, P=NS across groups by ANOVA
COLA II Change in DBP according to Age
80.7
80.5
79.6
75.4
74.0
74.6
0
25
50
75
100
? = -5.3 mmHg*
? = -6.5 mmHg*
? = -5.0 mmHg*
Baseline
6 months
>70- <75 years
(n=380)
75-79 years
(n=278)
> 80 years
(n=265)
*P<0.05, P=NS across groups by ANOVA
COLA II Change in HR according to Age
80.2
80.8
80.7
70.4
67.8
69.9
0
25
50
75
100
>70-<75 years
(n=379)
75-79 years