The treatment of chronic obstructive pulmonary disease (COPD, formerly known as emphysema or chronic bronchitis with airway obstruction) is a rapidly expanding 5 billion dollar per year market for inhaler manufacturers. Large COPD public awareness (promotional) campaigns were started in 2007 by the U.S. National Heart, Lung, and Blood Institute (NHLBI), and the manufacturers of the two inhalers which have been approved by the FDA for COPD: Spiriva (tiotropium) and high dose Advair (a combination of 500 mcg fluticasone and 50mcg salmeterol).
The results of INSPIRE, the second of three very large, international COPD treatment studies were published in the January 2008 issue of the most prestigious pulmonary journal (AJRCCM, aka “the blue journal”). INSPIRE directly compared the effectiveness and safety of these two inhalers in over 1300 patients with severe treated COPD for two years.
Twice as many patients randomly selected to take Spiriva died during the two years of the study when compared to those randomly selected to take Advair. In the patients who also had some type of heart disease or hypertension when they started the study (about half of them), there were 24 deaths in those taking Spiriva, but only 9 deaths in those taking Advair. The higher death rate in those taking Spiriva was apparent just three months into the study. Unfortunately, sudden death from heart disease in individual patients with COPD is rarely even considered as possibly due to a side-effect of their inhalers, because smoking is the most common cause of death from heart disease.
Over 8 million patients with COPD have been prescribed Spiriva since it became available five years ago. Spiriva temporarily relieves shortness of breath in about half of patients with severe COPD, and may slightly reduce the risk of a subsequent exacerbation in those who have previously required hospitalization for a COPD exacerbation. Some adults with asthma are prescribed Spiriva, but the evidence that it helps them is so scanty that the FDA has not approved it for asthma.
More than 15 years ago, I was an investigator of the NHLBI-sponsored Lung Health Study in which 5000 smokers with mild to moderate COPD were randomized to take Atrovent (ipratropium) or a placebo for five years. We reported that study participants taking Atrovent were twice as likely to die, and more likely to be hospitalized with a serious cardiac arrhythmia (heart rhythm disturbance) than those taking the placebo inhaler. Since then, other investigators have also reported that patients with COPD taking Spiriva were more likely to experience a cardiac arrhythmia. Spiriva and Atrovent are both anticholinergic bronchodilator inhalers, but Spiriva is ultra long-acting.
More than one-third of the patients who were enrolled into the INSPIRE study were current cigarette smokers — the cause of their severe lung disease. The study sponsors apparently did nothing to help them to stop smoking, although smoking cessation is the only treatment proven to halt the rapid progression of COPD. On the other hand, the study investigators did not include a placebo comparison group because “it was deemed unethical to withhold known effective therapies.”
I worry that prescribing expensive inhalers for patients with COPD who continue to smoke makes them think that they are “getting the cure” and don’t need to quit. All smokers should be helped with the process of smoking cessation.