Martin et al 1 suggest that caution should be exercised when prescribing long acting oral β agonists to patients at risk of cardiac failure, based on results from a prescription event monitoring (PEM) study.

Firstly, all β₂ agonists (short and long acting, oral and inhaled) should be used with caution in patients with severe cardiovascular disease, as is pointed out in the package insert for all drugs of this class.

Secondly, the study does not provide any evidence on this issue. PEM studies are not designed to study causal relations but to generate new hypotheses. Although the authors have made an attempt to consider several potential biases in the analyses, the study design is inappropriate compared with, for example, a prospective randomised controlled trial, and the results must be interpreted with great caution.

Thirdly, no support for an association between bambuterol and an increased risk for cardiac failure has been found in our review of preclinical studies, clinical studies (including >3000 patients/healthy volunteers), or post-marketing surveillance (based on >130 million treatment days).

Fourthly, according to the authors there have been no spontaneous reports of cardiac failure with bambuterol to the …