Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease

  • Review
  • Intervention

Authors


Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications, both of which are recommended in COPD guidelines. These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to assemble reliable evidence on their relative and additive effects.

Objectives

To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and LABA in patients with stable COPD. Comparisons were made between single agents and in combination versus LABAs alone.

Search methods

We searched the Cochrane Airways Group Specialised Register of Trials (July 2008) and reference lists of articles. We also contacted drug companies for relevant trial data.

Selection criteria

All randomised controlled trials comparing treatment for at least four weeks with an anticholinergic agent (ipratropium bromide) alone or in combination with LABA versus LABA alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD.

Data collection and analysis

Three review authors independently performed data extraction and study quality assessment. We contacted study authors and pharmaceutical companies for missing data.

Main results

Seven studies met the inclusion criteria of the review (2652 participants). Monotherapy comparison (six studies): There was a significantly greater change in favour of salmeterol in morning PEF and FEV1. There were no significant differences in quality of life, exacerbations, or symptoms. Formoterol appeared to confer some benefits over ipratropium treatment in terms of morning peak flow. Combination comparison (three studies): There was a significant improvement in post-bronchodilator lung function, supplemental short-acting beta-agonist use and HRQL in favour of combination therapy compared with salmeterol alone.

Authors' conclusions

The available data from the trials suggest that there is little difference between regular long term use of IpB alone and salmeterol if the aim is to improve COPD symptoms and exercise tolerance. However, salmeterol was more effective in improving lung function variables. In terms of post-bronchodilator lung function, combination therapy conferred modest benefits, a significant improvement in HRQL, and reduced supplemental short-acting beta-agonist requirement, although this effect was not consistent. Additional studies are needed to assess the relative effects of combining therapies, using validated subjective measurements, and should consider concordance and the convenience of people having to use different inhaler devices.

摘要

背景

Ipratropium bromide噴霧治療劑與LABA對於患有穩定性慢性阻塞性肺部疾病(stable chronic obstructive pulmonary disease)患者的效益

慢性阻塞性肺部疾病(COPD)對社區來說通常與高罹病率、高死亡率與高花費有關。患者通常會因使用LABA和抗乙醯膽鹼支氣管擴張劑(Anticholinergic bronchodilators)等藥物而使其症狀獲得改善。這兩種藥物都是COPD治療指引中的建議用藥,這些藥物對疾病有不同的作用機轉,理論上當這兩種藥物混合使用時應該有加乘的療效。當醫師開立這兩種藥物作為長期治療COPD的處方之前,先瞭解有關這兩種藥物合併使用後所產生相關及加乘作用的證據是很重要的。

目標

本研究比較患有穩定性COPD患者長期規律(至少4週以上)使用抗乙醯膽鹼支氣管擴張劑和LABA的相對效益及安全性。會針對單一藥物或混合藥物與單獨使用LABA的效果進行比較。

搜尋策略

我們檢索Cochrane Airways Group Specialised Register of Trials(2006年8月)及文獻的參考資料清單,並向藥廠索取相關試驗數據。

選擇標準

研究中納入單獨使用抗膽鹼製劑(anticholinergic agent,例如ipratropium bromide噴霧劑)或是將抗膽鹼製劑與LABA合併使用至少4星期以上,與單獨使用LABA的成效進行比較的試驗,這些藥劑是透過定量的吸入劑或噴霧器,提供患有穩定性COPD的非氣喘成人患者使用。

資料收集與分析

有3個審閱者分別獨立進行資料的萃取並評估研究方法的品質,我們也與試驗作者和藥廠聯繫以取得一些遺漏的數據。

主要結論

總共有7個試驗符合納入研究的標準(其中包含了2652名受試者),其中有6篇是針對單一療法進行比較:使用salmeterol的患者在清晨PEF值和FEV1值會產生明顯的變化,但是對於生活品質、症狀惡化或是症狀改變等試驗成果上並沒明顯的差異,使用Formoterol在清晨尖峰氣流量(Morning Peak Flow)的數值上,比使用ipratropium進行治療似乎可以展現更多的優勢,此外,有3個試驗是針對混用藥物進行比較:相對於單獨使用salmeterol,進行混合式藥物治療的患者在使用支氣管擴張劑後,肺部功能有明顯的改善,短效型β2增效劑的補充和健康相關生活品質(HRQL)等試驗成果上也具有較佳的表現。

作者結論

經由試驗中取得的可用數據可推測,當治療目標為改善COPD症狀和患者的運動耐受度時,長期規律使用IpB和salmeterol會產生些微的差異。然而,salmeterol對改善肺部功能變異具較明顯的效果。若要考量使用支氣管擴張劑後的肺部功能,選擇使用混合式藥物治療似乎可提供較為理想的效果,並且可使建科相關生回品值得分明顯進步,並降低補充短效型β2增效劑的需求。但此一效益並不一致。因此有必要藉由更多研究來評估混合式藥物治療的相對效果,並考量患者使用不同吸入裝置來進行實驗的一致性和便利性。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

本研究檢視比較常規使用不同類型支氣管擴張劑藥物(LABA和ipratropium)至少4星期,對患有COPD(或肺氣腫(emphysem)/慢性支氣管炎chronic bronchitis))患者的試驗,COPD是一種對社區會造成高罹病率、高死亡率和高成本的疾病,服用LABA和抗乙醯膽鹼支氣管擴張劑(ipratropium)的患者通常會覺症狀有所改善,這些藥物有不同的作用機轉,理論上當這些藥物被混合使用時對疾病的治療應可產生加乘作用。當這些藥物作為COPD的長期治療處方時,瞭解單獨開立ipratropium或是將其作為混合性藥物治療可以產生什麼樣的效益是很重要的。本研究總共納入7個試驗(2652名受試者),和ipratropium比較,Salmeterol較能改善肺部功能,但是這兩種藥物對症狀的反應並沒有明顯的差別。比較這兩種藥物混合式治療與單獨使用Salmeterol時,混合式藥物治療較改善生活品質,但其他的比較卻僅有微小且不一致的差異。本研究的發現無法提供使用ipratropium bromide和LABA治療COPD一個常規性的建議,但是混合性藥物治療較能提升健康狀態。在這個階段,患者應該使用可以提供較有效症狀改善的支氣管擴張劑,因此可以將混合性藥物治療列為治療的考量但是這種療法與其他吸入性治療方法(例如吸入式類固醇和tiotropium)的相對影響都仍屬於未知的狀態。成本也應該被列入選用治療方法的考量,因為支氣管擴張劑的價格不一。

Plain language summary

Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease

This review looks at studies that compare the regular use for at least four weeks of different types of bronchodilator medicine (long acting beta-2 agonist medicines and ipratropium) in people with stable chronic obstructive pulmonary disease (COPD, or emphysema/chronic bronchitis).

Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications (ipratropium). These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to know what benefit there are, if any, of prescribing ipratropium alone or as combination therapy over LABAs. Seven studies (2652 participants) were included. Salmeterol was more effective than ipratropium on lung function, but there were no major differences seen between the responses to ipratropium and salmeterol on symptoms. When we compared the combination of these two drugs with salmeterol, combination was superior to salmeterol in terms of quality of life, but the differences between these two treatments on other measurements were small and inconsistent. The findings of the review would not support a general recommendation for the use of ipratropium bromide over a beta-2 agonist alone in COPD, but the combination does confer greater benefit in health status. At this stage, people with COPD should use the bronchodilator that gives them the most improvement in their symptoms. Combination therapy should be considered, but the relative effects of this therapy in relation to other forms of inhaled therapy such as inhaled steroids and tiotropium are unknown. Cost considerations also need to be taken into account as there are considerable variations in price of bronchodilators.