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Scompenso cardiaco e BPCO: c’è spazio per i beta-bloccanti?
Dott. Enrico Strocchi
Prevalence and incidence of COPD
in Pts. with Heart Failure
61 practices with 377439 patients provided data to
the Primary Care Clinical Informatics Unit at the
University of Aberdeen
(Hawkins et Al, Eur J Heart Failure 2010)
650 GPs
909638 Pts.
39741 with Asthma
25281 with COPD
COPD = 628 Pts
Non-COPD =
4382 Pts
(Staszewsky et Al, J Cardiac Failure 2007)
(Staszewsky et Al, J Cardiac Failure 2007)
4133 Pts, hospitalized
with worsening HF
and EF≤40%
416 with COPD
(Mentz et Al, J
Cardiac Failure 2012)
HR = 1,42
(of dying)
HR = 1,26
(of non-fatal events)
(Macchia et Al, Eur J Heart Failure 2006)
(Pocock et Al, on behalf of
MAGGIC, Eur Heart J 2012)
405 Pts. >65 yrs
Follow-up = 4,2 yrs
(Boudestein et Al, Eur
J Heart Failure 2009)
A few preliminary thoughts…
• Epidemiological studies and everyday clinical
practice shows that COPD and CV diseases are
very often combined;
• The prognosis of CV diseases is worse when
COPD is also present;
• Intensive drug treatment of cardiac disease is
therefore necessary;
• Which are the possible effects of β-blockers in
patients with COPD?
Pharmacological characteristics of
-blockers
Nonselective
without ISA
Propranolol
Timolol
Nadolol
Sotalol
(antiarrhythmic)
Ibutmonide
(+ α-block)
Carvedilol
(+ α-block)
Nonselective
with ISA
Oxprenolol
Pindolol
Dilevalol
Prenaterol
Labetalol (+ α-block)
Carteolol
More selective
for B1-AR
without ISA
Atenolol
Metoprolol
Bisoprolol
Esmolol
Practolol
Pafenolol
Tolamolol
Bevantolol
More selective
for B1-AR
with ISA
Celiprolol (+ α-block)
Acebutolol
Xamoterol
(+ α-block)
Nebivolol
(da Matera et Al, Pulmonary Pharmacology & Therapeutics 2010)
-receptors’ distribution
1
2
Lung
10-30%
(sub-mucosal glands;
alveolar walls)
70-90%)
(bronchial smooth
muscle; alveolar
walls; inflammatory
cells
Heart
77%
23%
Atrial cells
60-70%
40-30%
Ventricular cells
70-80%
30- 20%
62%
38%
Tissue
Heart Failure
Impact of different classes of -blockers on
airways in patients with COPD
Drugs
Effect on Airway
Function
Effect on the
bronchodilator
response to inhaled
2-agonists



0/
Nonselective -blockers with ISA


More selective for 1-AR that modulate
the endogenous production of NO
0/
0/
Nonselective -blockers
1-selective
= mild decrease; =moderate decrease; =severe decrease; 0= no effect
(da Matera et Al, Pulmonary Pharmacology & Therapeutics 2010)
Properties of -blockers approved for
the treatment of HF
-blocker
1selectivity
Lipid
solubility
Route of
elimination
Half-life (h)
Carvedilol
1
Moderate
Hepatic
7-10
Metoprolol
tartrate
40
Moderate
Hepatic
3-7
Metoprolol
succinate
40
Moderate
Hepatic
20
Bisoprolol
75
Low
Hepatic/renal
10-12
Nebivolol
>300
High
Hepatic
12-19
(from Hawkins et Al, JACC 2011)
Differences among 1-selective -blockers
(Terbutaline 6 μg/Kg/h)
(Nuttall et al J Clin Pharm Ther 2003)
(Chang et Al, Int Med J 2010)
(FEV1 of subjects who commenced
the study on Carvedilol)
(Jabbour et Al, JACC 2010)
(from Hawkins et Al, JACC 2011)
(Staszewsky et Al, J Cardiac Failure 2007)
(Hatkins et Al JACC 2011)
Merit-HF
The only trial without COPD or use of bronchodilators
among the exclusion criteria
210 (5,3%) of the 3.991 patients included had a
documented diagnosis of COPD.
The incidence of pulmonary adverse events was similar
in metoprolol or placebo-treated groups: bronchospasm
0,3 vs 0,4%; COPD exacerbations (0,4 vs 0,4%);
respiratory tract infections (2,0% vs 1,9%).
Trends in -blocker prescribing in
patients with Heart Failure
(Hawkins et Al, Eur J Heart Failure 2010)
Prevalence of β-blockers use in HF patients in
Bologna (S.Orsola-Malpighi Hospital)
336 Pts. with HF discharged
from hospital in 2011
Standardized dose
2230 Pts. With COPD
Age 64,8 yrs
Follow-up 7,2 yrs
686 deaths
(Arch Intern Med 2010)
(Arch Intern Med 2010)
TARDIS
Tayside (Scotland)
5977 Pts.
Follow-up = 4,35 yrs
(Short et Al, 2011)
Adjusted hazard
ratios for all cause
mortality among
patients with
COPD divided
according to type
of treatment
(Short et Al, BMJ 2011)
2249 Pts. On long-term
oxygen therapy
Median follow-up 1,1 yrs
(Ekstrӧm et al, Am J Crit
Respir Care Med 2013)
To sum up:
• Patients with COPD are to be considered at higher
cardiovascular risk because of the consequences of
pulmonary disease;
• Therefore they deserve the “best preventive
treatment” to reduce their CV risk
• Treatment with β-blockers of patients with heart
failure and mild to moderate COPD is possible and it
reduces mortality and morbidity and it could possibly
reduce also COPD exacerbations but … RCT’s are
needed.