Oral vs IV Steroids for Acute Exacerbation of COPD
Oral vs IV Steroids for Acute Exacerbation of COPD
Hi, this is Andy Shorr from Washington, DC, with your Pulmonary and Critical Care Literature Update. I would like to bring to your attention an important issue that was reviewed in JAMA in the June 16 issue. In an article by Lindenauer and colleagues, we got a little bit more insight on how to approach our patients with acute exacerbations of COPD [chronic obstructive pulmonary disease].
Acute exacerbations remain associated with substantial morbidity and mortality and are a leading cause of admission for patients with COPD. One of our key components of care in these patients is corticosteroids. They are complemented, of course, by antibiotics and by bronchodilators, and we know from a number of meta-analyses that these 3 key aspects of care of the COPD exacerbation are crucial to improving outcomes.
When it comes to the management and utilization of corticosteroids, there has always been a controversy surrounding how to administer those corticosteroids. The best study looking at corticosteroids and COPD was done over a decade ago, the DVA Cooperative Study published in the New England Journal of Medicine, where patients were randomized to 125 mg of methylprednisolone several times a day vs placebo. That's a very aggressive dose of corticosteroids, and we certainly know that the high dose intravenous (IV) corticosteroids have a number of toxicities. We also know, in terms of direct anti-inflammatory effects, that oral corticosteroids tend to be as efficacious as intravenous corticosteroids.
However, we have no head-to-head studies really comparing IV vs oral corticosteroids in COPD exacerbations, and as you can imagine, that would be a difficult study to do. Therefore, Lindenauer and colleagues conducted a pharmacoepidemiologic analysis. They looked at approximately 80,000 patients admitted to US hospitals with COPD exacerbations and focused on how the steroids were utilized in those patients. They looked at patients given only IV or patients given only oral corticosteroids. The primary endpoint for this analysis was a composite endpoint, which included hospital mortality, need for mechanical ventilation, or readmission within 30 days.
When these authors looked among these 80,000 patients that they analyzed, about 90% were treated with intravenous corticosteroids; the remainder were treated with only corticosteroids during their hospital course. Overall, in terms of crude event rates, rates of hospital mortality, rates of readmission, and rates of need for mechanical ventilation, all were similar between the 2 groups.
Now, of course, these 2 groups are unequal with respect to many baseline characteristics, so these authors conducted 2 different approaches to try to adjust for those imbalances. One was a traditional multivariable analysis, which confirmed that there seemed to be no difference in outcomes between corticosteroids, whether they were given orally throughout the hospital stay or intravenously. Then, they used a propensity score to actually correct for the fact that perhaps people given oral corticosteroids were in some way systematically different than patients given IV corticosteroids, and they wanted to adjust for this kind of process of care confounder. Even after doing that and matching for that kind of propensity to be given one type of steroid vs another, the results were the same. In fact, they did even suggest that there were better outcomes, or a lower risk, for the composite endpoint than for patients given oral corticosteroids.
Now, I don't think, from this data -- the way it was analyzed and its limitations -- that we can ever say that oral corticosteroids alone are superior to intravenous corticosteroids, but I think they certainly say that they're no worse than or, perhaps, noninferior to them.
Now, one of the major limitations of any one of these analyses is that when you look at a large database, there are always issues about coding and diagnosis. Lots of patients with COPD exacerbations may really have been pneumonia admissions or what have you, and this is always a concern. But fortunately, with 80,000 patients, hopefully, the resolution we lose in terms of detail is made up for by power, and in terms of generalized ability.
In the end, I think the takeaway from this is that if you have patients who are candidates to receive oral corticosteroids while they're having a COPD exacerbation, even if they're hospitalized, that is certainly an acceptable option. If the patient's gut is not working, if they're intubated and what have you, and you need to give it intravenously, that's fine, too. But certainly, if you're going to give an IV, I think a quick step-down to oral is acceptable. And if you have the ability to do oral alone, because of the patient's gut, that's also acceptable as well.
In the end, clearly, corticosteroids remain important, but we need to learn better how to utilize them appropriately in the care of this common disease.
Thank you very much. This is Andy Shorr.
Hi, this is Andy Shorr from Washington, DC, with your Pulmonary and Critical Care Literature Update. I would like to bring to your attention an important issue that was reviewed in JAMA in the June 16 issue. In an article by Lindenauer and colleagues, we got a little bit more insight on how to approach our patients with acute exacerbations of COPD [chronic obstructive pulmonary disease].
Acute exacerbations remain associated with substantial morbidity and mortality and are a leading cause of admission for patients with COPD. One of our key components of care in these patients is corticosteroids. They are complemented, of course, by antibiotics and by bronchodilators, and we know from a number of meta-analyses that these 3 key aspects of care of the COPD exacerbation are crucial to improving outcomes.
When it comes to the management and utilization of corticosteroids, there has always been a controversy surrounding how to administer those corticosteroids. The best study looking at corticosteroids and COPD was done over a decade ago, the DVA Cooperative Study published in the New England Journal of Medicine, where patients were randomized to 125 mg of methylprednisolone several times a day vs placebo. That's a very aggressive dose of corticosteroids, and we certainly know that the high dose intravenous (IV) corticosteroids have a number of toxicities. We also know, in terms of direct anti-inflammatory effects, that oral corticosteroids tend to be as efficacious as intravenous corticosteroids.
However, we have no head-to-head studies really comparing IV vs oral corticosteroids in COPD exacerbations, and as you can imagine, that would be a difficult study to do. Therefore, Lindenauer and colleagues conducted a pharmacoepidemiologic analysis. They looked at approximately 80,000 patients admitted to US hospitals with COPD exacerbations and focused on how the steroids were utilized in those patients. They looked at patients given only IV or patients given only oral corticosteroids. The primary endpoint for this analysis was a composite endpoint, which included hospital mortality, need for mechanical ventilation, or readmission within 30 days.
When these authors looked among these 80,000 patients that they analyzed, about 90% were treated with intravenous corticosteroids; the remainder were treated with only corticosteroids during their hospital course. Overall, in terms of crude event rates, rates of hospital mortality, rates of readmission, and rates of need for mechanical ventilation, all were similar between the 2 groups.
Now, of course, these 2 groups are unequal with respect to many baseline characteristics, so these authors conducted 2 different approaches to try to adjust for those imbalances. One was a traditional multivariable analysis, which confirmed that there seemed to be no difference in outcomes between corticosteroids, whether they were given orally throughout the hospital stay or intravenously. Then, they used a propensity score to actually correct for the fact that perhaps people given oral corticosteroids were in some way systematically different than patients given IV corticosteroids, and they wanted to adjust for this kind of process of care confounder. Even after doing that and matching for that kind of propensity to be given one type of steroid vs another, the results were the same. In fact, they did even suggest that there were better outcomes, or a lower risk, for the composite endpoint than for patients given oral corticosteroids.
Now, I don't think, from this data -- the way it was analyzed and its limitations -- that we can ever say that oral corticosteroids alone are superior to intravenous corticosteroids, but I think they certainly say that they're no worse than or, perhaps, noninferior to them.
Now, one of the major limitations of any one of these analyses is that when you look at a large database, there are always issues about coding and diagnosis. Lots of patients with COPD exacerbations may really have been pneumonia admissions or what have you, and this is always a concern. But fortunately, with 80,000 patients, hopefully, the resolution we lose in terms of detail is made up for by power, and in terms of generalized ability.
In the end, I think the takeaway from this is that if you have patients who are candidates to receive oral corticosteroids while they're having a COPD exacerbation, even if they're hospitalized, that is certainly an acceptable option. If the patient's gut is not working, if they're intubated and what have you, and you need to give it intravenously, that's fine, too. But certainly, if you're going to give an IV, I think a quick step-down to oral is acceptable. And if you have the ability to do oral alone, because of the patient's gut, that's also acceptable as well.
In the end, clearly, corticosteroids remain important, but we need to learn better how to utilize them appropriately in the care of this common disease.
Thank you very much. This is Andy Shorr.
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