COPD, how long should I treat an exacerbation??

We have all treated COPD exacerbations and many of us know what the recommendations are, but Dr. Cutrell reminded us during VA morning report to consider the background literature for these decisions. International guidelines advocate a 7-14 day course of systemic glucocorticoids, while some propose a shorter term treatment regimen can be as effective.

In 2013, JAMA came out with the REDUCE trial listed below. Here are some highlights:

http://jama.jamanetwork.com/article.aspx?articleid=1688035

The REDUCE trial (Reduction in the Use of Corticosteroids in Exacerbated COPD) compared short term vs conventional glucocorticoid therapy in acute exacerbations of COPD patients.

Study design: Randomized, non-inferiority, double-blinded, multi-center trial in 5 swiss teaching hospitals. 314 patients with acute COPD were enrolled.

Interventions: Patients were randomized to 40 mg of prednisone for 14 days vs 5 days

Measured outcomes: Time to next exacerbation within 180 days

Results: 

– Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis.

– Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion.

– In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of −1.2% (95% CI, −12.2% to 9.8%) between the short-term and the conventional.

– Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional.

– There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function.

– In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently.

Conclusions: In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.