Transcript La Cardiopatia Ischemica Cronica

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MANAGEMENT OF BPCO AND COMORBIDITIES
Treatment of Chronic
Heart Failure in patients
with COPD
Claudio Ceconi, Ferrara
Modena
2 March 2011
Clinical guidelines are...
 Definition:
“Systematically developed statements to
assist practitioner and patient decisions
about appropriate health care for specific
clinical circumstances”
Institute of Medicine, 1990
 Other common names:
 medical guidelines
 clinical practice guidelines
 clinical protocols
“
”
 Frequent and challenging
diagnosis
 Prognosis is worsened
 Natriuretic peptides may be
useful
 ACE-inh, BBlockers, ARBs
are useful
 Asthma contraindicates
BBlockers
 Re-habilitation appropriate to
improve skeletal muscle
function and fatigue
No Evidence Based
recommendation !
Global Strategy for Diagnosis,
Management and Prevention of COPD






Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Management
Practical Considerations
PubMed: 1996 to date
 Chronic pulmonary disease
AND heart failure
= 2767
 Chronic pulmonary disease
AND heart failure
NOT Cor Pulmonale
NOT BNP
= 396
Factors determining different outcomes
of Patients
1. Chance
2. Accuracy of data sources: do they describe
accurately the real world?
3. Risk associated to specific diseases
4. Differences in the efficiency of care and
therapies and of quality of the treatments
Iezzoni I. “Risk adjustment for measuring healthcare outcomes”
Health Administration Press, 1997
CHF
Pts enrolled in clinical trials vs real world
Variable
RCT
Age
57-64
Sx M:F
4:1
EF > 40%
Exclusion criteria
AF
20%
Renal Dysfunction
Exclusion criteria
Co-morbidity
Uncommon
Disability
Exclusion criteria
Drugs
At target
Compliance
High
Therapy duration
1-3 years
Primary objective
Survival
Mortality at 1 year
9-12%
“Real World” ?
Comorbidity and guidelines
conflicting interests
 Guidelines are likely to introduce more problems
than they solve when used in patients with
comorbidity (25-50% of people with chronic
diseases)
 Given the problems of exclusion criteria,
randomization, blinding etc…, studies that combine
therapeutic approaches and/or report the natural
course of patients with comorbidities are welcome.
Lancet 2006; 367: 550
Comorbidity and guidelines
conflicting interests
 Guidelines are likely to introduce more problems
than they solve when used in patients with
comorbidity (25-50% of people with chronic
diseases)
 Given the problems of exclusion criteria,
randomization, blinding etc…, studies that combine
therapeutic approaches and/or report the natural
course of patients with comorbidities are welcome.
Lancet 2006; 367: 550
CHF&COPD: Ignored combination
 Risk ratio of developing CHF is 4.5 in COPD
 FEV1 is as good predictor of cardiovascular
mortality as serum cholesterol
 Tobacco use
 Global epidemics
 Almost half of people aged 65 yrs or more: at least 3
chronic medical conditions
Rutten FH. Am Heart J 2002;143:412-7, O’Connor CM.J Card Fail 2005;11:200-5, Gustaffson F. Eur Heart J 2004;25:129-35
 Cross-sectional study, patients 65 years of age
 Of 405 participating patients with a diagnosis of
chronic obstructive pulmonary disease, 83 (20.5%,
95% CI 16.7–24.8) had previously unrecognized heart
failure
Prevalence of COPD in patients with HF
Reference
Prevalence % Country
n
Population
Data source
Bangdiwala
15
USA, Canada
6273
HF hospitalisation
SOLVD Registry
Auerbach
19
USA
1298
HF hospitalisation
SUPPORT Study
Vaccarino
27
USA
2445
HF hospitalisation
Conneticut Peer Review
Org
Gambassi
19
USA
86 094
outpatient
SAGE Database
Baker
25
USA
23 505
HF hospitalisation
Cleveland Health
Quality Choice
Program
Kosiborod
33
USA
3 957 520
HF hospitalisation
Medicare
Havranek
33
USA
34 587
HF hospitalisation
National Heart Failure
Project
Kamalesh
52
USA
495
outpatient
Indianapolis Veterans
Affairs Medical Centre
Lee
21
Canada
2624
HF hospitalisation
EFFECT study
Brown
12
Scotland
27 477
HF hospitalisation
Scottish Morbidity
Record
Gustaffson
22
Denmark
5491
HF hospitalisation
DIAMOND-CHF
Registry
Factors determining different outcomes
of Patients
1. Chance
2. Accuracy of data sources: do they describe
accurately the real world?
3. Risk associated to specific diseases
4. Differences in the efficiency of care and
therapies and of quality of the treatments
Iezzoni I. “Risk adjustment for measuring healthcare outcomes”
Health Administration Press, 1997
Non-cardiac Comorbidity Increases Preventable
Hospitalizations among Medicare Beneficiaries with
CHF A survey of 122 630 Subjects Aged > 65 years
Any hospItalisation
ACSC
CHF ACSC
1
Probability
0,8
0,6
0,4
0,2
0
0
1
2
3
4
5
ACSC = Ambulatory Care Sensitive (e.g. preventable)
Condition
6
7
8
9
10
Overall
Braunstein et al., JACC 2003;42:1226
Adjusted 5-year survival curves for patients
with HF with and without COPD
Rusinaru D et al AJC 2008
Centro Scompenso - Università Ferrara
 A cohort of 118 patients consecutively screened
in an outpatient HF clinic
 New diagnosis of CHF
 ≥ 65 years of age
 Smoking history of ≥ 10 pack-years
Characteristics of the study population
Total patients
(n = 118)
Age (yrs)
Male (n [%])
72.6 ± 6.8
86%
Smoking status (n [%])
Ex-smokers
79.6%
Current smokers
20.4%
Etiology of HF (n [%])
Hypertension
16%
Coronary heart disease
64%
Idiopathic Cardiomyopathy
18%
Other and unknown
2%
Prevalence of COPD and COPD severity
% of patients
100
31%
69%
80
60
40
20
0
C H F + C OP D
CHF
GOLD I
GOLD II
GOLD III
GOLD: Global Obstructive Lung disease
All but two of the patients were unaware of COPD
Characteristics of patients with CHF according to
presence or absence of COPD
COPD
No COPD
Age (yrs)
(n=36)
73.8 ± 7.1
(n=82)
72.1 ± 6.6
Pack-years
49.2 ± 31
39.2 ± 22.2
0.16
Body mass index (Kg/m2)
Dyspnoea (MMRC score)
NYHA class I and II (%)
27.6 ± 3.8
1 ± 0.5
83.3
28.4 ± 3.6
1 ± 0.4
94.5
N.S.
N.S.
N.S.
LVEF ≤ 40% (%)
Diabetes (%)
Hyperlipidaemia (%)
Hypertension (%)
Metabolic syndrome (%)
Serum creatinine (mg/dL)
Hemoglobin (g/dL)
63.3
23.3
60
100
63
1.7 ± 0.3
13.1 ± 0.3
60.3
24.7
65.8
98.6
63.5
1.4 ± 0.2
13.3 ± 0.2
N.S.
N.S.
N.S.
N.S.
N.S.
N.S.
N.S.
HsCRP (mg/dL)
0.8 ± 0.3
0.6 ± 0.1
N.S.
p value
N.S.
PaO2
90
85.6
85
p=0.004
79.3
80
CHF
CHF + BPCO
75
70
CHF
CHF + BPCO
Correlation between lung function and
echocardiography data
DT (ms)
sPAP (mmHg)
r
value
p
value
r
value
p
value
FEV1 pre-bronchodilator
0.34
0.004
-0.33
0.006
FEV1 post-bronchodilator
0.35
0.003
-0.28
0.020
FVC pre-bronchodilator
0.36
0.003
-0.34
0.005
FVC post-bronchodilator
0.33
0.01
-0.45
0.001
TlCO (% predicted)
0.39
0.004
-0.47
0.001
(% predicted)
(% predicted)
(% predicted)
(% predicted)
FEV1= forced expiratory volume in 1 second; FVC= forced vital capacity; TlCO= diffusing capacity of carbon monoxide;
DT= E velocity deceleration time; sPAP= systolic pulmonary pressure.
Baseline: Indexes of Severity
NT-proBNP
6mwd
P<0.01
4000
3540
400
3500
P=0.05
350
3000
2500
2000
375
333
300
1640
250
1500
1000
200
CHF
CHF + BPCO
CHF
CHF + BPCO
CHF
CHF + BPCO
FOLLOW UP
% NT-proBNP
% 6mwd
P<0.01
100%
100%
25%
80%
20%
15%
60%
15%
40%
10%
20%
5%
0%
0%
CHF
CHF + BPCO
25%
-1%
CHF
CHF + BPCO
FOLLOW UP
% FEV1 Post % Predicted
0%
% FEV1/FCV
0%
-0.2%
-0.5%
-2%
-2%
-4%
-4%
-6%
-6%
-8%
-8%
-8%
P<0.01
-1%
FOLLOW UP
% FEV1 Post % Predicted
0%
% PaO2
0%
-0.2%
+ 0.5%
-2%
-2%
-3%
-4%
-4%
-6%
-6%
-8%
-8%
P<0.01
-8%
Survival
1
CHF
0,8
CHF+BPCO
p = 0,12
0,6
0
5
Months
15
20
25
SURVIVAL OF INCIDENT CASES OF
HEART FAILURE
Cowie et al. 2002
All Cause Death + Hospitalization
Predictive power of anaemia
Time to the first event
Factors determining different outcomes
of Patients
1. Chance
2. Accuracy of data sources: do they describe
accurately the real world?
3. Risk associated to specific diseases
4. Differences in the efficiency of care and
therapies and of quality of the treatments
Iezzoni I. “Risk adjustment for measuring healthcare outcomes”
Health Administration Press, 1997
-blockers in
heart failure all-cause mortality
Survival
1.0
US Carvedilol Study
Carvedilol
(n=696)
0.9
Placebo
(n=398)
0.8
Risk reduction = 65%
0.7
p<0.001
0.6
0.5
0 50 100 150 200 250 300 350 400
Days
Mortality %
20
Survival
1.0
CIBIS-II
Packer et al (1996)
MERIT-HF
Placebo
Bisoprolol
15
0.8
Metoprolol CR/XL
10
Risk reduction = 34%
Placebo
Risk reduction = 34%
5
0.6
p=0.0062
p<0.0001
0
0
0
200
400
Time after inclusion (days)
600
800
Lancet (1999)
0
3
6
9
12 15
Months of follow-up
18
21
The MERIT-HF Study Group (1999)
Cardioselective beta-blockers for chronic
obstructive pulmonary disease
FEV1 treatment effect
S.R. Salpeter et al. Respiratory Medicine 2002
Safety of beta-blockers
 Selective B1B should not be withheld in
patients with moderate-to-severe COPD
 Real life: less than 10% of CHF patients with
COPD recieve BB
Betablocker prescriptions by age from
1995 to 2004
65.9%
IN
CHF
2001-2004 BRING-UP 1-2
p<0.0001
53.4%
39.9%
53.6%
41.1%
1995-1997
1998-2000
28.6%
25.1%
18.1%
23.4%
14.7%
11.9%
7.4%
14.1%
8.8%
1.1%
<65 years
65-74 years
75-84 years
85 years
Total
p<0.0001
2001-2004
BRING-UP Study
REASONS WHY TREATMENT WAS NOT STARTED
(n. 1455)
n. of pts
CONTRAINDICATIONS
540 (37.1%)
COPD
317 (59%)
PVD
76 (14%)
First degree AV block (>28 sec)
35 (6%)
Advanced AV block
22 (4%)
CHF on treatment with IV inotropes
38 (7%)
HR <50 bpm
39 (7%)
SBP 90 mmHg
50 (9%)
Note: It was possible to specify more than one reason
B-Blockade in CHF
CHF+COPD
CHF
COPD co-morbidity did not predict the tolerability nor
the achievement of target dose of -Blocker therapy
Concomitant use of BB with inhaled
beta-agonists
 B2B agonists (short acting?) increase risk for
CHF decompensation and all-cause mortality
in CHF
 Combination with nonselective BB: beneficial?
 Both selective and nonselective BB with alpha
blockade are to be avoided during COPD
exacerbation due to the insufficient safety data
Au DH. Chest 2003;123:1964-9
ACE inhibitors
 Cornerstone of treatment in CHF
 May prevent SM atrophy and improve
respiratory muscle strength
 No increased risk of cough and bronchospasm
Morbidity/Mortality Reduction in COPD
effect of RAS inhibition and Statins
COPD
Hospitalization
Infarction or
Death
Mancini et al. JACC 2006
From common pathways to novel treatment
options (too early and too speculative?)
Can all COPD patients profit from cardiovascular drugs?
- Renin-Angiotensin-Aldosteron System (ACE-i or ARB)
- Sympathic nervous system (betablockers)
- Endothelial function and atherosclerosis (statins)
=> New generation mortality reducing drugs in COPD ?
Rutten FH
Comorbidity, Ageing
Chronic diseases and human illness
Research units
Department of Cardiology
University of Ferrara
Ceconi C, Fucili A, Ferrari R
Department of Respiratory Diseases
University-Hospital of Ferrara
Potena A, Ballerin L, Papi A
Department of Respiratory Diseases
University of Modena & Reggio Emilia
Fabbri LM
Department of Clinical and Experimental Medicine
University of Ferrara
Boschetto P, Stendardo M, Concordia A