Cardioselective beta-blockers for reversible airway disease

Background

Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.

Objectives

To assess the effect of cardioselective beta-blockers in patients with asthma or chronic obstructive pulmonary disease (COPD).

Search strategy

We performed a search of EMBASE, MEDLINE and CINAHL up to June 2007 using the terms: (adrenergic* and antagonist*) or (adrenergic* and block*) or (adrenergic* and beta-receptor*) or (beta-adrenergic* and block*) or (beta-blocker* and adrenergic*) or (blockader* or Acebutolol or Alprenolol or Atenolol or Betaxolol or Bisoprolol or Bupranolol or Butoxamine or Carteolol or Celiprolol or Dihydroalprenolol or Iodocyanopindolol or Labetalol or Levobunolol or Metipranolol or Metoprolol or Nadolol or Oxprenolol or Penbutolol or Pindolol or Practolol or Propranolol or Sotalol or Timolol)

Selection criteria

Randomized, blinded, placebo-controlled trials of single dose or continued treatment of the effects of cardioselective beta-blockers in patients with reversible airway disease.

Data collection and analysis

Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. We divided beta1-blockers into those with or without intrinsic sympathomimetic activity (ISA). Interventions were: administration of single dose or continued beta1-blocker, and response to beta2-agonist given after the study drug.

Main results

Nineteen studies on single-dose treatment and 10 studies on continued treatment met the inclusion criteria. Single dose cardioselective beta-blocker produced a 7.46% (95% CI, 5.59 to 9.32%) reduction in forced expiratory volume in 1 second (FEV1), but with a 4.63% (95% CI, 2.47 to 6.78%) increase in FEV1 with beta2-agonist, compared to placebo. Treatment lasting three to 28 days produced no change in FEV1 (-0.42%; 95% CI, -3.74 to 2.91%), symptoms or inhaler use, whilst maintaining a 8.74% (95% CI, 1.96 to 15.52%) response to beta2-agonist. There was no significant change in FEV1 treatment effect for those patients with COPD: single doses -5.28% (95% CI, -10.03 to -0.54%), continued treatment 1.07% (95% CI, -3.3 to 5.44%).

With continued treatment there was no significant difference in FEV1 response for beta1-blockers without ISA compared to those with ISA: -3.22% (95%CI, -7.79 to 1.36%) compared to 2.72% (95% CI, -2.12 to 7.59%). Those without ISA produced a 12.0% increase in FEV1 after beta2-agonist administration compared to placebo (95%CI, 4.12 to 19.87%) while beta1-blockers with ISA produced no change compared to placebo (-0.60% [95%CI, -13.93 to 12.73%). These results were obtained in a small number of studies of few patients. The difference was not significant.

Authors' conclusions

Cardioselective beta-blockers given in mild to moderate reversible airway disease or COPD, do not produce adverse respiratory effects in the short term. Given their demonstrated benefit in conditions such as heart failure, cardiac arrhythmias and hypertension, these agents should not be withheld from such patients. Long term safety (especially their impact during an acute exacerbation) still needs to be established.