Intervention Review
Phosphodiesterase III inhibitors for heart failure
Editorial Group: Cochrane Heart Group
Published Online: 21 JAN 2009
Assessed as up-to-date: 31 OCT 2004
DOI: 10.1002/14651858.CD002230.pub2
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Amsallem E, Kasparian C, Haddour G, Boissel JP, Nony P. Phosphodiesterase III inhibitors for heart failure. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD002230. DOI: 10.1002/14651858.CD002230.pub2.
Publication History
- Publication Status: Edited (no change to conclusions)
- Published Online: 21 JAN 2009
Abstract
Background
In the treatment of chronic heart failure, vasodilating agents, ACE inhibitors and beta-blockers have shown an increase of life expectancy. Another strategy is to increase the inotropic state of the myocardium : phosphodiesterase inhibitors (PDIs) act by increasing intra-cellular cyclic AMP, thereby increasing the concentration of intracellular calcium, and lead to a positive inotropic effect.
Objectives
This overview on summarised data aims to review the data from all randomised controlled trials of PDIs III versus placebo in symptomatic patients with chronic heart failure. The primary endpoint is total mortality. Secondary endpoints are considered such as cause-specific mortality, worsening of heart failure (requiring intervention), myocardial infarction, arrhythmias and vertigos. We also examine whether the therapeutic effect is consistent in the subgroups based on the use of concomitant vasodilators, the severity of heart failure, and the type of PDI derivative and/or molecule. This overview updates our previous meta-analysis published in 1994.
Search methods
Randomised trials of PDIs versus placebo in heart failure were searched using MEDLINE (1966 to 2004 January), EMBASE (1980 to 2003 December), Cochrane CENTRAL trials (The Cochrane Library Issue 1, 2004) and McMaster CVD trials registries, and through an exhaustive handsearching of international abstracting publications (abstracts published in the last 22 years in the "European Heart Journal", the "Journal of the American College of Cardiology" and "Circulation").
Selection criteria
All randomised controlled trials of PDIs versus placebo with a follow-up duration of more than three months.
Data collection and analysis
21 trials (8408 patients) were eligible for inclusion in the review. 4 specific PDI derivatives and 8 molecules of PDIs have been considered.
Main results
As compared with placebo, treatment with PDIs was found to be associated with a significant 17% increased mortality rate (The relative risk was 1.17 (95% confidence interval 1.06 to 1.30; p<0.001). In addition, PDIs significantly increase cardiac death, sudden death, arrhythmias and vertigos.
Considering mortality from all causes, the deleterious effect of PDIs appears homogeneous whatever the concomitant use (or non-use) of vasodilating agents, the severity of heart failure, the derivative or the molecule of PDI used.
Authors' conclusions
Our results confirm that PDIs are responsible for an increase in mortality rate compared with placebo in patients suffering from chronic heart failure. Currently available results do not support the hypothesis that the increased mortality rate is due to additional vasodilator treatment. Consequently, the chronic use of PDIs should be avoided in heart failure patients.
Plain language summary
Phosphodiesterase III inhibitor class drugs taken orally and long term are associated with increased deaths in heart failure
A number of options are available to treat symptomatic chronic heart failure. These include ACE inhibitors, beta-blockers and spironolactone, which result in an increase of life expectancy. Another strategy is to increase the strength of the pumping action of the heart as with digitalis and with phosphodiesterase III inhibitors. The review clearly showed evidence that people treated for chronic heart failure for three months or more with phosphodiesterase III inhibitors were more likely to die than people given an inactive placebo treatment.
摘要
背景
Phosphodiesterase III inhibitors 治療心臟衰竭
在慢性心臟衰竭的治療上, 血管擴張劑, ACE inhibitors及betablocker 皆可增加平均壽命。另外一個策略則是增加心肌的收縮力: phosphodiesterase inhibitors (PDIs) 可增加細胞內的cyclic AMP而增加胞內的鈣離子濃度, 終至增強心臟收縮力。
目標
這篇概括性文章總結了所有隨機對照試驗針對PDIsIII於具有臨床症狀之慢性心衰竭病人身上之效益。主要試驗指標是總死亡率, 而次要指標評估指標則是原因別死亡率， 其包括惡化之心臟衰竭(需要臨床處置), 心肌梗塞, 心率不整及眩暈。我們也檢查了基於以下分類之子分群上的療效是否一致: 併用其它血管擴張劑, 心衰竭之嚴重度, PDI衍生物及或其分子之種類. 這篇概括性文章更新了我們之前在1994年發表的統合分析。
搜尋策略
我們在以下資料庫搜索關於 PDIs 比較安慰劑在心臟衰竭應用上之隨機對照試驗: MEDLINE (1966年至2004年 January), EMBASE (1980年至2003年 December), Cochrane CENTRAL trials (The Cochrane Library Issue 1, 2004年) and McMaster CVD trials registries, 及針對以下透過徹底的手動搜尋: 國際上發表之摘要(該摘要必須為近22年內發表於“European Heart Journal, the Journal of the American College of Cardiology and Circulation”).
選擇標準
關於 PDIs 比較安慰劑在心臟衰竭應用上之隨機對照試驗, 其追蹤期至少3個月。
資料收集與分析
符合文獻回顧資格之試驗共21個 (8408位病患). 其中探討4個 PDI 特化衍生物及 8種PDI分子。
主要結論
跟安慰劑比較, PDIs治療與增加17%的死亡率有相關(相對危險性 1.17 (95% CI 1.06∼1.30; p<0.001)。)。此外PDIs顯著的增加心臟致死、瘁死、心率不整及眩暈。細究全原因死亡率，PDIs的損害效無論在使用(未使用)血管擴張劑，心臟衰竭之嚴重度，使用的PDIs衍生物及分子皆為一致。
作者結論
我們的結果確認在慢性心臟衰竭病患身上，相對於服用安慰劑組，PDIs的使用導致死亡率的增加。目前可得的結果並不支持死亡率的增加源自於額外的血管擴張效應此假設。結論是應該避免於心臟衰竭病患身上持續使用PDIs。
翻譯人
本摘要由臺北榮民總醫院楊勝翔翻譯。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
總結
長期口服Phosphodiesterase III inhibitor此類的藥物與增加心臟衰竭的死亡率有關聯性。在治療有症狀的慢性心臟衰竭上有許多可獲得的選擇，包括ACE inhibitors，betablockers 及spironolactone，這些藥物可延長平均壽命。其它的策略是增強心收縮力比如使用digitalis(毛地黃)及phosphodiesterase III inhibitors。這篇文章明確的呈現出證據關於在慢性心臟衰竭病患使用3個月以上的phosphodiesterase III inhibitors，相較於安慰劑組)，會導致較高之死亡率。