In this entry, I would like to discuss some recent findings on two similar medications that have significantly changed the landscape of asthma treatment (both from the clinician and patient perspectives). Salmeterol (brand name: Serevent) and formoterol (brand name: Foradil) are long acting bronchodilators in the beta-2 agonist class. They help open narrowed breathing tubes by relaxing the smooth muscle around the breathing tubes, reducing wheeze and shortness of breath. They are often used in asthmatics because they last longer (about 12 hours) than "short-acting" beta agonists (also known as quick-relief inhalers) like albuterol, pirbuterol, and salbutamol (among others). Salmeterol is the long-acting bronchodilator used in combination with fluticasone (a corticosteroid) in the combo drug Advair.
Recent studies have found an association between the use of salmeterol/formoterol and serious adverse events at an increased rate compared to patients taking a placebo. Interestingly, most of these adverse events involved worsening asthma control.
What did the studies show?
There have been many studies on the efficacy and safety of salmeterol and formoterol in asthma. Most of these studies have shown that both drugs are effective to improve asthma symptoms. In addition, some have found that the rate of adverse events, including those related to asthma control, were increased in patients taking salmeterol or formoterol compared to a placebo inhaler (an inhaler which appears identical to an inhaler with medication but has only inert powder without medication).
More recent studies have combined the results of these studies to add power to the analysis by grouping results from many similar studies. These grouped studies, called meta-analyses, have found that the rate of serious adverse events was greater in patients taking salmeterol or formoterol compared to patients receiving placebo. Of note, there was no difference in mortality between the groups.
These findings, in large samples of patients, are clearly cause for attention on the part of patients and clinicians alike. Both of these medications are used by many asthmatics because they are effective -- they improve asthma symptoms and, for many patients, decrease the need to use quick-relief inhalers. But are they "safe?" On one hand, any medication that leads to an increase in adverse events could be thought of as less safe than not taking the medication at all. However, would patients and clinicians choose a medication that makes them feel better even if the risk of adverse events is increased? Furthermore, how common are the adverse events compared to how much better patients' asthma is under improved control?
In my opinion, speaking in general terms as I cannot give specific advice to patients in this forum, salmeterol and formoterol are effective medications that significantly improve asthma control. And there are suggestions in the studies that some of the adverse events were related to improper use of these medications. Whether formoterol or salmeterol are right for your asthma can only be decided in discussing these issues with your asthma care provider.
Over the past months, I have discussed both current and cutting edge treatments for asthma. In some cases, new treatments become the so-called "standard of care" as they work well for most asthmatics at the main goals of asthma treatment -- reducing symptoms and minimizing asthma flares or exacerbations. For some standard treatments, more information about their safety comes to light well after they are approved by government regulatory agencies and accepted by practitioners.
The salmeterol and formoterol story is not the first time this issue has come up in asthma care. For example, this occurred with older short-acting beta agonists (e.g. isoproterenol) in the 1970s, when there was concern that while these medications helped control asthma symptoms, they increased the risk of death from asthma. The lesson to be learned is that good medicines need to be continually reassessed not only for whether they continue to benefit patients well after they become available, but also whether there are safety issues that might change their utility even while making patients feel better.