Beta blocker in COPD - precedents in heart failure
To the Editor,
with the greatest interest I have read the recent retrospective
cohort study on the use of beta-blocker in COPD. Analyzing a large
longitudinal Scottish database the authors describe a significant and
robust reduction in morbidity and mortality in patients with COPD being
prescribed a beta blocker 1. Importantly lung function did not
deteriorate. Concerning the underlying pathophysiology the authors
discussed "that up-regulation of beta2 adrenoceptors by chronic beta
blockade may improve the effectiveness of beta2 agonists". While this is
certainly appealing, the concept of neurohumoral activation might
contribute to the positive effects of beta blockade in COPD as detailed
below.
With a variety of methods we and others described striking
neurohumoral activation in patients with COPD 2 3 4. From patients with
heart failure it is well known, that beta blocker reduce mortality and
morbidity by their impact on sympathetic and neurohumoral activation. Thus
it is intriguing to speculate that beta blocker exerts their beneficial
effects in COPD patients via the autonomic nervous system. Indeed, also
ACE inhibitors and angiotensin receptor blocker (being successfully used
to treat heart failure) also show positive effects in COPD 5 6.
One might consider historic parallels concerning the use of beta
blocker in heart failure and COPD. Only two decades ago beta blocker were
considered contraindicated in patients with heart failure due to their
negative inotropic and chronotropic effects. Large randomized controlled
trials have subsequently clearly demonstrated positive effects of beta
blockade in patients with heart failure. These positive results being
explained by the blockade of maladaptive neurohumoral activity on the
cardiovascular system 7. Of note pharmacologic therapy coined at
neurohumoral activation needs more than a few weeks to reveal its overall
positive effects. The present study informs us about the need and how to
perform a randomized controlled trial of beta blocker in COPD 8.
Yours sincerely
Stefan Andreas
Prof. Dr. med. Stefan Andreas
Lungenfachklinik Immenhausen, Krs Kassel
Gastprofessor
Universitaetsmedizin Goettingen
Abteilung Kardiologie und Pneumologie www.herzzentrum-goettingen.de
References
1. Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect
of beta blockers in treatment of chronic obstructive pulmonary disease: a
retrospective cohort study. Bmj 2011;342:d2549.
2. Andreas S, Anker SD, Scanlon PD, Somers VK. Neurohumoral
activation as a link to systemic manifestation of chronic lung disease.
Chest 2005;128:3618-3624.
4. Luethje L, Raupach T, Michels H, Unsold B, Hasenfuss G, Kogler H,
et al. Exercise intolerance and systemic manifestations of pulmonary
emphysema in a mouse model. Respir Res 2009;10(1):7.
5. Raupach T, Luethje L, Koegler H, Duwe C, Schweda F, Hasenfuss G,
et al. Effects of angiotensin II type 1 receptor blockade on pulmonary and
systemic manifestations in an emphysema mouse model. Pulm Pharmac Ther
2011 24:215-20.
6. Mortensen EM, Copeland LA, Pugh MJ, Restrepo MI, de Molina RM,
Nakashima B, et al. Impact of statins and ACE inhibitors on mortality
after COPD exacerbations. Respir Res 2009;10:45.
7. Schrier RW, Abraham WT. Hormones and hemodynamics in heart
failure. N Engl J Med 1999;341:577-85.
8. Kazani S, Israel E. Treatment with beta blockers in people with
COPD. Bmj 2011;342:d2655.
Competing interests:
No competing interests
28 August 2011
Stefan Andreas
Director
Lungenfachklinik Immenhausen, Krs. Kassel. Associate Professor Universitaetsmedizin Goettingen
Rapid Response:
Beta blocker in COPD - precedents in heart failure
To the Editor,
with the greatest interest I have read the recent retrospective
cohort study on the use of beta-blocker in COPD. Analyzing a large
longitudinal Scottish database the authors describe a significant and
robust reduction in morbidity and mortality in patients with COPD being
prescribed a beta blocker 1. Importantly lung function did not
deteriorate. Concerning the underlying pathophysiology the authors
discussed "that up-regulation of beta2 adrenoceptors by chronic beta
blockade may improve the effectiveness of beta2 agonists". While this is
certainly appealing, the concept of neurohumoral activation might
contribute to the positive effects of beta blockade in COPD as detailed
below.
With a variety of methods we and others described striking
neurohumoral activation in patients with COPD 2 3 4. From patients with
heart failure it is well known, that beta blocker reduce mortality and
morbidity by their impact on sympathetic and neurohumoral activation. Thus
it is intriguing to speculate that beta blocker exerts their beneficial
effects in COPD patients via the autonomic nervous system. Indeed, also
ACE inhibitors and angiotensin receptor blocker (being successfully used
to treat heart failure) also show positive effects in COPD 5 6.
One might consider historic parallels concerning the use of beta
blocker in heart failure and COPD. Only two decades ago beta blocker were
considered contraindicated in patients with heart failure due to their
negative inotropic and chronotropic effects. Large randomized controlled
trials have subsequently clearly demonstrated positive effects of beta
blockade in patients with heart failure. These positive results being
explained by the blockade of maladaptive neurohumoral activity on the
cardiovascular system 7. Of note pharmacologic therapy coined at
neurohumoral activation needs more than a few weeks to reveal its overall
positive effects. The present study informs us about the need and how to
perform a randomized controlled trial of beta blocker in COPD 8.
Yours sincerely
Stefan Andreas
Prof. Dr. med. Stefan Andreas
Lungenfachklinik Immenhausen, Krs Kassel
Gastprofessor
Universitaetsmedizin Goettingen
Abteilung Kardiologie und Pneumologie
www.herzzentrum-goettingen.de
References
1. Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect
of beta blockers in treatment of chronic obstructive pulmonary disease: a
retrospective cohort study. Bmj 2011;342:d2549.
2. Andreas S, Anker SD, Scanlon PD, Somers VK. Neurohumoral
activation as a link to systemic manifestation of chronic lung disease.
Chest 2005;128:3618-3624.
3. Raupach T, Bahr F, Herrmann P, Luethje L, Heusser K, Hasenfuss G,
et al. Slow breathing reduces sympathoexcitation in COPD. Eur Respir J
2008;32(2):387-392.
4. Luethje L, Raupach T, Michels H, Unsold B, Hasenfuss G, Kogler H,
et al. Exercise intolerance and systemic manifestations of pulmonary
emphysema in a mouse model. Respir Res 2009;10(1):7.
5. Raupach T, Luethje L, Koegler H, Duwe C, Schweda F, Hasenfuss G,
et al. Effects of angiotensin II type 1 receptor blockade on pulmonary and
systemic manifestations in an emphysema mouse model. Pulm Pharmac Ther
2011 24:215-20.
6. Mortensen EM, Copeland LA, Pugh MJ, Restrepo MI, de Molina RM,
Nakashima B, et al. Impact of statins and ACE inhibitors on mortality
after COPD exacerbations. Respir Res 2009;10:45.
7. Schrier RW, Abraham WT. Hormones and hemodynamics in heart
failure. N Engl J Med 1999;341:577-85.
8. Kazani S, Israel E. Treatment with beta blockers in people with
COPD. Bmj 2011;342:d2655.
Competing interests: No competing interests