Dataset Information

Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.

ABSTRACT:

Background

Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality. Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations. However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate. The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.

Materials and methods

We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.

Results

Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out. Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24-0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45-0.78; P<0.01). Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months. In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance. The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50). Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).

Conclusion

Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner. However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance. Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks.

SUBMITTER: Cui Y

PROVIDER: S-EPMC6254503 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.

Cui Yanan Y Luo Lijuan L Li Chenbei C Chen Ping P Chen Yan Y

International journal of chronic obstructive pulmonary disease 20181122

<h4>Background</h4>Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality. Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations. However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate. The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.<h4>Materials and methods</h4>We compre ...[more]

PMID: 30538443

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Project description:BackgroundObservational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.MethodsIn this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.ResultsA total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.ConclusionsAmong patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

Project description:BackgroundThe majority of patients with chronic obstructive pulmonary disease (COPD) suffer from comorbid cardiovascular (CV) disease. Accumulating evidence suggests a temporal association between COPD exacerbations and acute CV events, possibly due to lung hyperinflation, increased hypoxemia and systemic inflammation. The aims of the study were to estimate the risk of (1) acute CV events [acute myocardial infarction (AMI), CV-related death] or stroke in the months following a COPD exacerbation and (2) COPD exacerbation in the months following an acute CV event.MethodsA systematic literature review of observational studies published since 2000 was conducted by searching literature databases (Medline and Embase). Studies were eligible if conducted in adults with COPD, exposed to either COPD exacerbation or acute CV events, with outcomes of acute CV events or COPD exacerbation reported. Studies were appraised for relevance, bias and quality. Meta-analyses, using random-effect models, were performed for each outcome of interest, thus providing a pooled relative risk (RR) and its 95% confidence interval.ResultsEight studies were identified, of which seven were used for the meta-analyses examining the risk of CV events 1-3 months after an exacerbation compared with none. For stroke (six studies), RR was 1.68 (95% CI = 1.19-2.38). For AMI (six studies), RR was 2.43 (95% CI = 1.40-4.20). No studies exploring risk of exacerbation following an acute CV event were identified.ConclusionThis meta-analysis identified a markedly increased risk of stroke or AMI within a relatively short period of time following a COPD exacerbation. Although the underlying mechanisms are not fully elucidated, patients with COPD should be monitored for risk of CV outcomes after exacerbations. In addition, preventing exacerbations may decrease the risk of subsequent acute CV events.RegistrationThe study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42020211055).

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Dataset Information

Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.

Background

Materials and methods

Results

Conclusion

Publications

Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.

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