Mar 162014

Once upon a time in 1964, it was noted that propranolol, a nonselective beta-blocker, could precipitate severe bronchospasm in patients with asthma, especially at high doses. Additional small studies showed propranolol and other nonselective beta blockers could increase airway resistance. British guidelines advise avoiding beta blockers in asthma generally. As a result, beta blockers are often withheld from people with asthma or COPD who might benefit (i.e., those with congestive heart failure or past myocardial infarction).

More recent evidence from multiple observational studies suggests newer, cardioselective beta blockers appear safe and might even be beneficial in people with COPD, potentially reducing mortality and exacerbations. However, in a randomized trial (BLOCK-COPD), patients taking beta-blockers had more-severe COPD exacerbations, on average.

As for asthma, chronic use of cardioselective beta blockers doesn't seem to precipitate asthma attacks in mild or moderate asthma. A 2002 meta-analysis in Annals Internal Medicine showed that a single dose of beta blocker did reduce asthmatics' FEV1 by ~7.5% predicted, but this decrement went away with chronic use. They concluded "Cardioselective beta-blockers do not produce clinically significant adverse respiratory effects in patients with mild to moderate reactive airway disease ... cardioselective beta-blockers should not be withheld from patients with mild to moderate reactive airway disease." (That analysis did also conclude that nonselective beta-blocker use reduced FEV1, FVC, and bronchodilator response to ß-agonist, but without noticeable increase in subjective respiratory symptoms or need for ß-agonist inhalers.) A 2014 meta-analysis of 32 studies suggested more caution, reporting that 1 in 8 asthmatics exposed to selective beta blockers had an acute drop >20% in FEV1. That analysis could not report on chronic use of beta blockers, nor exacerbation risk.

Chronic use of beta blockers, including nonselective beta blockers like nadolol, may actually improve bronchodilator response to albuterol, through as-yet undetermined effects.

A very small randomized trial suggested that even nonselective beta blockers (propranolol) may be safer than previously believed for patients with mild to moderate asthma.

Authors randomized 18 patients taking inhaled corticosteroids for mild to moderate asthma to receive propranolol up to 80 mg or placebo for 6-8 weeks in a crossover design study. Patients continued their inhaled steroids and were also given tiotropium, presumably as a safety measure. At trial's end, there were no significant differences between groups in airway hyperresponsiveness or asthma symptoms, although there was a 2.4% reduction in FEV1 predicted after chronic beta-blocker usage.

Beta blockers are a key component of care for people who have had previous heart attacks or who have systolic heart failure. Three beta blockers have demonstrated a survival benefit in systolic heart failure: the cardioselective agents metoprolol XL and bisoprolol, and the noncardioselective carvedilol. It seems unlikely that the risks of worsening asthma or COPD outweigh the potential benefits of beta blocker use, in these patients.

Beta blockers have not been proven beneficial in randomized trials for stable coronary artery disease (primary prevention in people without a previous myocardial infarction or who have risk factors). The theorized benefit among these patients drives the vast majority of beta-blocker prescriptions, but there is today no evidence-based imperative for this practice. So aside from asthma/COPD patients with prior heart attacks or systolic heart failure -- almost all of whom should receive beta blockers, as a rule -- this is a mostly academic debate.

What's more interesting is the question of whether chronic beta blocker use might actually improve asthma or COPD, as mounting observational evidence suggests. Enough safety data has accumulated that such prospective studies could be done ethically. There are a few small studies listed on testing beta blockers for asthma or COPD. We'll keep you posted.

Philip Short et al. Randomized Placebo-controlled Trial to Evaluate Chronic Dosing Effects of Propranolol in Asthma". Am J Resp Crit Car Med, Vol. 187, No. 12 (2013), pp. 1308-1314.

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Beta blockers safe for most patients with asthma or COPD?