Note: This is a multi-article spread containing a shared commentary. Please scroll down for the other article(s).
Therapeutics
Review: Systemic corticosteroids reduce treatment failure but increase hyperglycemia in COPD exacerbations Clinical impact ratings:
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多多多多多夞夞
Walters JA, Tan DJ, White CJ, et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD001288.
多多多多多多夞
多多多多多夞夞
Questions
Review methods
Are systemic corticosteroids (SCSs) effective for treating acute exacerbations of chronic obstructive pulmonary disease (COPD)? How do parentally and orally administered SCSs compare?
Cochrane Airways Group Specialised Register of trials (Jun 2013), which includes studies identified from Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE/Excerpta Medica, CINAHL, AMED, PsycINFO, and hand-searches of respiratory journals and meeting abstracts; MEDLINE (Jun 2012 to Jun 2013); EMBASE/Excerpta Medica (2010 to Jun 2013); and reference lists, www.clinicaltrials.gov, and www.who.int/ictrp/en/ were searched for randomized controlled trials (RCTs). 20 RCTs (n = 2085, mean age 68 y, median 82% men) met the selection criteria. 16 RCTs compared SCSs with placebo, and 4 compared parenteral and oral SCSs. Trials were done in inpatient hospital settings, hospital intensive care units, emergency departments, and outpatient clinics. 14 RCTs had adequately generated randomization sequences, 10 had adequate allocation concealment, and 13 were double-blind.
Review scope Included studies compared parenteral or oral SCSs with placebo, or compared parenteral and oral SCSs, in patients who had acute functional deterioration due to COPD exacerbation and were treated in primary care or in hospital. Studies of patients with acute asthma were excluded. Outcomes included treatment failure (need to intensify therapy or return to emergency department or hospital), relapse, death, and adverse drug effects.
Main results
Systemic corticosteroids (SCSs) for exacerbations of chronic obstructive pulmonary disease* Outcomes
Number of trials (n)
Weighted event rates SCS
Placebo
RRR (95% CI)
NNT (CI)
9 (7 to 14)
Treatment failure
9 (917)
15%
27%
43% (26 to 56)
Relapse at 1 to 4 mo
5 (582)
12%
17%
28% (⫺6 to 51)
NS
12 (1319)
5%
5%
0% (⫺57 to 37)
NS
2 (415)
NA
NA
Death at 30 d
Hazard ratio (CI) Relapse at 30 d
0.78 (0.63 to 0.97)
NA
RRI (CI)
NNH (CI)
Adverse drug effects
8 (736)
41%
28%
44% (21 to 70)
6 (4 to 10)
Hyperglycemia
6 (804)
25%
12%
99% (51 to 163)
7 (5 to 12)
IV SCS
Oral SCS
RRR (CI)
NNT
Treatment failure
3 (298)
11%
16%
30% (⫺26 to 61)
NS
Relapse after treatment period
3 (298)
15%
16%
4% (⫺64 to 44)
NS
RRI (CI)
NNH
Death after discharge (1 to 3 mo)
3 (298)
3.7%
2.7%
39% (⫺55 to 330)
NS
Hyperglycemia
1 (40)
55%
20%
175% (5 to 620)
3 (2 to 15)†
*NA = not available; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from data in article using a fixed-effect model. †Calculated from data in article using a fixed-effect model.
Commentary The SCS efficacy review by Walters and colleagues supports the use of these drugs for the treatment of COPD exacerbations, but the benefits are small and not without risk. Improvement in lung function with SCSs was not apparent beyond 72 hours, and length of hospital stay was reduced by just > 1 day compared with placebo. No reductions were found for duration of ventilator support or short-term mortality, although the latter may reflect the low death rate observed in the primary studies, possibly due to recruitment bias. Such a bias may not be important in this context because the risk– benefit ratio would still justify treatment in patients with the most severe disease.
Compared with placebo, SCSs reduced treatment failure and relapse at 30 days but not relapse at 1 to 4 months or death at 30 days (Table). SCSs increased risk for adverse drug effects (Table). IV and oral SCSs did not differ for treatment failure, relapse, or death after discharge, but IV SCSs increased risk for hyperglycemia more than oral SCSs (Table).
Conclusions Systemic corticosteroids (SCSs) reduce treatment failure but not death and increase hyperglycemia in acute exacerbations of chronic obstructive pulmonary disease compared with placebo. IV and oral SCSs do not differ for treating exacerbations, but IV SCSs increase risk for hyperglycemia. Source of funding: National Health and Medical Research Council, Australia. For correspondence: Dr. J.A.E. Walters, University of Tasmania, Hobart, Tasmania, Australia. E-mail [email protected].
glycemia (number needed to harm of 6 for adverse drug effects), so patients were more likely to have a side effect than avoid a treatment failure. There was no evidence for a benefit of parenteral over oral SCS, and because the latter is a safer means of administration, the review favors the oral route. Most trials in the review included hospitalized patients, but data from the smaller number of outpatient trials suggest a similar treatment response in this setting. No information was provided about patient subgroups, but it is reasonable to use oral SCSs only in patients who have worsening breathlessness that is clearly affecting their daily activities.
(continued on page 7)
Set against the reduction in treatment failure (number needed to treat of 9), there were significant risks, particularly for hyper姝 2015 American College of Physicians JC6 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
Annals of Internal Medicine
17 March 2015
Therapeutics
Review: ≤ 7 and > 7 days of systemic corticosteroids do not differ for efficacy in COPD exacerbations Clinical impact ratings:
多多多多多夞夞
多多多多多多夞
多多多多多多夞
Walters JA, Tan DJ, White CJ, Wood-Baker R. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;12: CD006897.
多多多多多夞夞
Question In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), is short-duration therapy with systemic corticosteroids (SCSs) as effective as longer-duration therapy?
Review scope Included studies compared SCS therapy for ≤ 7 days with therapy for > 7 days in adults with acute COPD exacerbations. Studies of patients with asthma or other lung diseases were excluded unless data for patients with COPD only were provided separately. Outcomes included treatment failure (need for additional treatment, return to emergency department or hospital, or unscheduled physician visit), relapse, death, and adverse drug effects.
Review methods Cochrane Airways Group Register of Trials (Jun 2014), which includes studies identified from Cochrane Central Register of
Controlled Trials, MEDLINE, EMBASE/Excerpta Medica, CINAHL, AMED, PsycINFO, and hand-searches of respiratory journals and meeting abstracts; MEDLINE, EMBASE/Excerpta Medica, CINAHL, and Cochrane Central Register of Controlled Trials (Mar 2014); and reference lists, www.clinicaltrials.gov, and www.who.int /ictrp/en/ were searched for randomized controlled trials (RCTs). 8 RCTs (n = 582, mean age 65 to 73 y, 58% to 94% men) met the selection criteria; all were set in hospitals. Short-duration therapies were 3, 5, or 7 days; longer-duration therapies were 10, 14, or 15 days. 4 RCTs had adequately generated randomization sequences, 4 had adequate allocation concealment, and 4 were double-blind.
Main results Short- and longer-duration treatment with SCSs did not differ for treatment failure, relapse, death, hyperglycemia, or hypertension (Table).
Conclusion
Short- (≤ 7 d) vs longer- (> 7 d) duration therapy with systemic corticosteroids in acute exacerbations of chronic obstructive pulmonary disease* Outcomes
Number of trials (n)
Weighted event rates Short
Longer
RRR (95% CI)
NNT
Treatment failure
4 (457)
6.3%
8.3%
26% (⫺42 to 62)
Not significant
Death
2 (336)
6.7%
7.7%
8% (⫺95 to 57)
Not significant
Hyperglycemia
2 (345)
44%
44%
1% (⫺25 to 21)
Not significant
Hypertension
1 (311)
9.6%
15%
35% (⫺19 to 65)
Not significant
Relapse
4 (478)
31%
30%
RRI (CI)
NNH
3% (⫺21 to 34)
Not significant
In patients with acute exacerbations of chronic obstructive pulmonary disease, short- and longer-duration therapies with systemic corticosteroids did not differ for treatment failure or death. Source of funding: National Health and Medical Research Council, Australia. For correspondence: Dr. J.A.E Walters, University of Tasmania, Hobart, Tasmania, Australia. E-mail [email protected].
*Abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from data in article using a fixed-effect model.
Commentary (continued from page 6) The studies in the SCS efficacy review by Walters and colleagues generally used a medium-high dose of SCSs (≥ 30 mg prednisolone equivalent) for ≥ 7 days. Walters and colleagues' second review addressed the question of whether treatment duration matters. The review included 8 RCTs that compared treatment for ≤ 7 days with treatment for > 7 days and included only patients with severe exacerbations. Most trials were small, so the meta-analyses were dominated by the results of the emergency department– based REDUCE trial (1), which contributed > 50% of the patients in the efficacy and adverse event analyses. REDUCE found that 5 days of prednisone, 40 mg/d, was noninferior to the same dose for 14 days (1). The trial was of good size (n = 314) and quality, and there was little evidence of heterogeneity between it and
the smaller studies. Thus, this result is probably reliable. A 5-day course of SCSs seems to be adequate. Paul Jones, MBBS St. George's, University of London London, England, UK Reference 1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-31.
17 March 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
JC7
姝 2015 American College of Physicians
Therapeutics
Review: Systemic corticosteroids reduce treatment failure but increase hyperglycemia in COPD exacerbations Clinical impact ratings:
多多多多多多夞
多多多多多夞夞
Walters JA, Tan DJ, White CJ, et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD001288.
多多多多多多夞
多多多多多夞夞
Questions
Review methods
Are systemic corticosteroids (SCSs) effective for treating acute exacerbations of chronic obstructive pulmonary disease (COPD)? How do parentally and orally administered SCSs compare?
Cochrane Airways Group Specialised Register of trials (Jun 2013), which includes studies identified from Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE/Excerpta Medica, CINAHL, AMED, PsycINFO, and hand-searches of respiratory journals and meeting abstracts; MEDLINE (Jun 2012 to Jun 2013); EMBASE/Excerpta Medica (2010 to Jun 2013); and reference lists, www.clinicaltrials.gov, and www.who.int/ictrp/en/ were searched for randomized controlled trials (RCTs). 20 RCTs (n = 2085, mean age 68 y, median 82% men) met the selection criteria. 16 RCTs compared SCSs with placebo, and 4 compared parenteral and oral SCSs. Trials were done in inpatient hospital settings, hospital intensive care units, emergency departments, and outpatient clinics. 14 RCTs had adequately generated randomization sequences, 10 had adequate allocation concealment, and 13 were double-blind.
Review scope Included studies compared parenteral or oral SCSs with placebo, or compared parenteral and oral SCSs, in patients who had acute functional deterioration due to COPD exacerbation and were treated in primary care or in hospital. Studies of patients with acute asthma were excluded. Outcomes included treatment failure (need to intensify therapy or return to emergency department or hospital), relapse, death, and adverse drug effects.
Main results
Systemic corticosteroids (SCSs) for exacerbations of chronic obstructive pulmonary disease* Outcomes
Number of trials (n)
Weighted event rates SCS
Placebo
RRR (95% CI)
NNT (CI)
9 (7 to 14)
Treatment failure
9 (917)
15%
27%
43% (26 to 56)
Relapse at 1 to 4 mo
5 (582)
12%
17%
28% (⫺6 to 51)
NS
12 (1319)
5%
5%
0% (⫺57 to 37)
NS
2 (415)
NA
NA
Death at 30 d
Hazard ratio (CI) Relapse at 30 d
0.78 (0.63 to 0.97)
NA
RRI (CI)
NNH (CI)
Adverse drug effects
8 (736)
41%
28%
44% (21 to 70)
6 (4 to 10)
Hyperglycemia
6 (804)
25%
12%
99% (51 to 163)
7 (5 to 12)
IV SCS
Oral SCS
RRR (CI)
NNT
Treatment failure
3 (298)
11%
16%
30% (⫺26 to 61)
NS
Relapse after treatment period
3 (298)
15%
16%
4% (⫺64 to 44)
NS
RRI (CI)
NNH
Death after discharge (1 to 3 mo)
3 (298)
3.7%
2.7%
39% (⫺55 to 330)
NS
Hyperglycemia
1 (40)
55%
20%
175% (5 to 620)
3 (2 to 15)†
*NA = not available; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from data in article using a fixed-effect model. †Calculated from data in article using a fixed-effect model.
Commentary The SCS efficacy review by Walters and colleagues supports the use of these drugs for the treatment of COPD exacerbations, but the benefits are small and not without risk. Improvement in lung function with SCSs was not apparent beyond 72 hours, and length of hospital stay was reduced by just > 1 day compared with placebo. No reductions were found for duration of ventilator support or short-term mortality, although the latter may reflect the low death rate observed in the primary studies, possibly due to recruitment bias. Such a bias may not be important in this context because the risk– benefit ratio would still justify treatment in patients with the most severe disease.
Compared with placebo, SCSs reduced treatment failure and relapse at 30 days but not relapse at 1 to 4 months or death at 30 days (Table). SCSs increased risk for adverse drug effects (Table). IV and oral SCSs did not differ for treatment failure, relapse, or death after discharge, but IV SCSs increased risk for hyperglycemia more than oral SCSs (Table).
Conclusions Systemic corticosteroids (SCSs) reduce treatment failure but not death and increase hyperglycemia in acute exacerbations of chronic obstructive pulmonary disease compared with placebo. IV and oral SCSs do not differ for treating exacerbations, but IV SCSs increase risk for hyperglycemia. Source of funding: National Health and Medical Research Council, Australia. For correspondence: Dr. J.A.E. Walters, University of Tasmania, Hobart, Tasmania, Australia. E-mail [email protected].
glycemia (number needed to harm of 6 for adverse drug effects), so patients were more likely to have a side effect than avoid a treatment failure. There was no evidence for a benefit of parenteral over oral SCS, and because the latter is a safer means of administration, the review favors the oral route. Most trials in the review included hospitalized patients, but data from the smaller number of outpatient trials suggest a similar treatment response in this setting. No information was provided about patient subgroups, but it is reasonable to use oral SCSs only in patients who have worsening breathlessness that is clearly affecting their daily activities.
(continued on page 7)
Set against the reduction in treatment failure (number needed to treat of 9), there were significant risks, particularly for hyper姝 2015 American College of Physicians JC6 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
Annals of Internal Medicine
17 March 2015
Therapeutics
Review: ≤ 7 and > 7 days of systemic corticosteroids do not differ for efficacy in COPD exacerbations Clinical impact ratings:
多多多多多夞夞
多多多多多多夞
多多多多多多夞
Walters JA, Tan DJ, White CJ, Wood-Baker R. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;12: CD006897.
多多多多多夞夞
Question In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), is short-duration therapy with systemic corticosteroids (SCSs) as effective as longer-duration therapy?
Review scope Included studies compared SCS therapy for ≤ 7 days with therapy for > 7 days in adults with acute COPD exacerbations. Studies of patients with asthma or other lung diseases were excluded unless data for patients with COPD only were provided separately. Outcomes included treatment failure (need for additional treatment, return to emergency department or hospital, or unscheduled physician visit), relapse, death, and adverse drug effects.
Review methods Cochrane Airways Group Register of Trials (Jun 2014), which includes studies identified from Cochrane Central Register of
Controlled Trials, MEDLINE, EMBASE/Excerpta Medica, CINAHL, AMED, PsycINFO, and hand-searches of respiratory journals and meeting abstracts; MEDLINE, EMBASE/Excerpta Medica, CINAHL, and Cochrane Central Register of Controlled Trials (Mar 2014); and reference lists, www.clinicaltrials.gov, and www.who.int /ictrp/en/ were searched for randomized controlled trials (RCTs). 8 RCTs (n = 582, mean age 65 to 73 y, 58% to 94% men) met the selection criteria; all were set in hospitals. Short-duration therapies were 3, 5, or 7 days; longer-duration therapies were 10, 14, or 15 days. 4 RCTs had adequately generated randomization sequences, 4 had adequate allocation concealment, and 4 were double-blind.
Main results Short- and longer-duration treatment with SCSs did not differ for treatment failure, relapse, death, hyperglycemia, or hypertension (Table).
Conclusion
Short- (≤ 7 d) vs longer- (> 7 d) duration therapy with systemic corticosteroids in acute exacerbations of chronic obstructive pulmonary disease* Outcomes
Number of trials (n)
Weighted event rates Short
Longer
RRR (95% CI)
NNT
Treatment failure
4 (457)
6.3%
8.3%
26% (⫺42 to 62)
Not significant
Death
2 (336)
6.7%
7.7%
8% (⫺95 to 57)
Not significant
Hyperglycemia
2 (345)
44%
44%
1% (⫺25 to 21)
Not significant
Hypertension
1 (311)
9.6%
15%
35% (⫺19 to 65)
Not significant
Relapse
4 (478)
31%
30%
RRI (CI)
NNH
3% (⫺21 to 34)
Not significant
In patients with acute exacerbations of chronic obstructive pulmonary disease, short- and longer-duration therapies with systemic corticosteroids did not differ for treatment failure or death. Source of funding: National Health and Medical Research Council, Australia. For correspondence: Dr. J.A.E Walters, University of Tasmania, Hobart, Tasmania, Australia. E-mail [email protected].
*Abbreviations defined in Glossary. Weighted event rates, RRR, RRI, and CI calculated from data in article using a fixed-effect model.
Commentary (continued from page 6) The studies in the SCS efficacy review by Walters and colleagues generally used a medium-high dose of SCSs (≥ 30 mg prednisolone equivalent) for ≥ 7 days. Walters and colleagues' second review addressed the question of whether treatment duration matters. The review included 8 RCTs that compared treatment for ≤ 7 days with treatment for > 7 days and included only patients with severe exacerbations. Most trials were small, so the meta-analyses were dominated by the results of the emergency department– based REDUCE trial (1), which contributed > 50% of the patients in the efficacy and adverse event analyses. REDUCE found that 5 days of prednisone, 40 mg/d, was noninferior to the same dose for 14 days (1). The trial was of good size (n = 314) and quality, and there was little evidence of heterogeneity between it and
the smaller studies. Thus, this result is probably reliable. A 5-day course of SCSs seems to be adequate. Paul Jones, MBBS St. George's, University of London London, England, UK Reference 1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-31.
17 March 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
JC7
姝 2015 American College of Physicians
