For COPD Patients Without Heart Disease, Risks of Beta Blockers Outweigh Benefits

Beta blockers are a widely used class of drugs for treating hypertension (high blood pressure). The Food and Drug Administration (FDA) also has approved certain beta blockers for treating patients who have had a heart attack or have chest pain due to coronary artery disease (angina), heart failure or migraines (see Table, below).

These drugs can be divided into two groups: those that work primarily by binding to beta receptors in the heart (cardioselective beta blockers) and those that act by binding to beta receptors throughout the body, including those in the heart and in the lungs (non-cardioselective beta blockers).

Examples of Oral Beta Blockers Available in the U.S.

†Brand-name combination products were excluded.
*Designated as Limited Use. Only cardioselective at dosages of 10 milligrams (mg) daily or less. At dosages higher than 10 mg daily, nebivolol loses its selectivity and blocks the beta receptors throughout the body.

It has been well-established that use of beta blockers after a heart attack or the development of heart failure in the general patient population decreases the risk of death in the long term.[1],[2] However, for many years, because of concerns that beta blockers may also cause sudden worsening of chronic obstructive pulmonary disease (COPD) due to acute bronchospasm (narrowing of the airways in the lungs leading to wheezing and shortness of breath), use of these drugs in COPD patients was avoided, even after a heart attack or the onset of heart failure. Importantly, there is now a large body of evidence indicating that COPD patients who have suffered a heart attack are more likely to survive longer if they are treated with beta blockers.[3],[4],[5]

But some observational studies also have suggested that treating COPD patients with beta blockers — even in the absence of heart disease — may decrease the risk of acute COPD exacerbations or flare-ups (episodes of sudden, sustained worsening of respiratory symptoms beyond normal day-to-day variations) and death.[6],[7] However, results of a recent well-designed randomized clinical trial published in the New England Journal of Medicine (NEJM) strongly refute the use of beta blockers in such patients with moderate-to-severe COPD who do not have heart disease.

COPD treatment

Stable COPD patients are managed by reducing exposure to factors that can damage the lungs, particularly smoking, and taking long-acting beta agonist bronchodilator drugs (such as formoterol [PERFOROMIST] and salmeterol [SEREVENT]), which open up the airways.[8] An important goal in the management of COPD is to reduce the occurrence of acute COPD exacerbations, which are characterized by increased shortness of breath, sputum production, cough and wheezing.

COPD exacerbations typically require additional treatments, such as taking short-acting beta agonist “rescue inhaler” bronchodilators (such as albuterol [PROAIR, PROVENTILHFA, VENTOLIN HFA]) and a short course of corticosteroids. Additionally, severe COPD exacerbations may necessitate hospitalization.

The NEJM trial[9]

In the trial, which was published in the NEJM on Dec. 12, 2019, researchers at 26 medical centers across the U.S. enrolled 532 subjects between the ages of 40 and 85 years who had been diagnosed with moderate-to-severe COPD. Notably, they excluded patients who had a proven cardiovascular reason for using a beta blocker (other than hypertension), including a prior heart attack and heart failure with decreased heart pumping. The subjects were randomly assigned to receive either a cardioselective beta blocker (extended release metoprolol [KAPSPARGO SPRINKLE, TOPROL-XL]) or a placebo once daily for up to 50 weeks.

The researchers found no significant difference between the two groups in the median time to the first COPD exacerbation of any severity during the treatment period, the primary outcome of the trial. However, subjects in the metoprolol group were more likely to have severe or very severe COPD exacerbations (exacerbations that led to hospitalization) than those in the placebo group. Moreover, 11 subjects in the metoprolol group died during the treatment period, whereas only five subjects in the placebo group died (seven of the deaths in the metoprolol group were attributed to COPD, compared with only one death in the placebo group).

The researchers found no significant difference between the two groups in the median time to the first COPD exacerbation of any severity during the treatment period, the primary outcome of the trial. However, subjects in the metoprolol group were more likely to have severe or very severe COPD exacerbations (exacerbations that led to hospitalization) than those in the placebo group. Moreover, 11 subjects in the metoprolol group died during the treatment period, whereas only five subjects in the placebo group died (seven of the deaths in the metoprolol group were attributed to COPD, compared with only one death in the placebo group).

What You Can Do

If you have COPD and have previously suffered a heart attack or heart failure, you should take a cardioselective beta blocker unless you are unable to tolerate such treatment. But if you have COPD and have not previously suffered a heart attack and do not have heart failure, you should not take metoprolol or any other beta blocker. Discuss these recommendations with your doctor. Never stop taking a prescription medication without first talking to your doctor.
 

References

[1] Freemantle N, Cleland J, Young P, et al. β blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318 (June 26):1730-1737.

[2] Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: The Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). JAMA. 2000;283(10):1295-1302.

[3] Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998;339(8):489-497.

[4] Chen J, Radford MJ, Wang Y, et al. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. J Am Coll Cardiol. 2001;37(7):1950-1956.

[5] Quint JK, Herrett E, Bhaskaran K, et al. Effects of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. BMJ. 2013 Nov 22;347:f6650.

[6] Du Q, Sun Y, Ding N, et al. Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies. PLoS One. 2014; 9(11): e113048.

[7] Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax. 2016;71(1):8-14.

[8] Global Initiative for Chronic Obstructive Lung Disease, Inc. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2019. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed March 5, 2020.

[9] Dransfield MT, Voelker H, Bhatt SP, et al. Metoprolol for the prevention of acute exacerbations of COPD. N Engl J Med. 2019;381(24):2304-2314.