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 GPs909638 Pts.39741 with Asthma25281 with COPD

(Staszewsky et Al, J Cardiac Failure 2007)

COPD = 628 PtsNon-COPD = 4382 Pts

(Staszewsky et Al, J Cardiac Failure 2007)

(Mentz et Al, J Cardiac Failure 2012)

4133 Pts, hospitalized with worsening HF and EF≤40%416 with COPD

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)

(Boudestein et Al, Eur J Heart Failure 2009)

405 Pts. >65 yrsFollow-up = 4,2 yrs

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

Nonselective with ISA

More selective for B1-AR

without ISA

More selective for B1-AR

with ISA

PropranololTimololNadololSotalol (antiarrhythmic)Ibutmonide (+ α-block)Carvedilol (+ α-block)

OxprenololPindololDilevalolPrenaterolLabetalol (+ α-block)Carteolol

AtenololMetoprololBisoprololEsmololPractololPafenololTolamololBevantolol (+ α-block)Nebivolol

Celiprolol (+ α-block)AcebutololXamoterol

(da Matera et Al, Pulmonary Pharmacology & Therapeutics 2010)

-receptors’ distribution

Tissue 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%

Heart Failure 62% 38%

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

Nonselective -blockers 1-selective 0/Nonselective -blockers with ISA More selective for 1-AR that modulate the endogenous production of NO

0/ 0/

(da Matera et Al, Pulmonary Pharmacology & Therapeutics 2010)

= mild decrease; =moderate decrease; =severe decrease; 0= no effect

Properties of -blockers approved for the treatment of HF

-blocker 1-selectivity

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

(Nuttall et al J Clin Pharm Ther 2003)(Terbutaline 6 μg/Kg/h)

(Chang et Al, Int Med J 2010)

(Jabbour et Al, JACC 2010)(FEV1 of subjects who commenced the study on Carvedilol)

(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)

Standardized dose

336 Pts. with HF discharged from hospital in 2011

2230 Pts. With COPDAge 64,8 yrsFollow-up 7,2 yrs686 deaths

(Arch Intern Med 2010)

(Arch Intern Med 2010)

(Short et Al, 2011)

TARDISTayside (Scotland)5977 Pts.Follow-up = 4,35 yrs

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 therapyMedian 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.