Diuretics for heart failure

 

Abstract

Background

Chronic heart failure is a major cause of morbidity and mortality world-wide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear.

Objectives

To assess the harms and benefits of diuretics for chronic heart failure

Search methods

We searched the Cochrane Central Register of Controlled Trials (Issue 2 2008), MEDLINE (1966 to June 2008), EMBASE (1980 to June 2008) and HERDIN database (1990 to June 2008). We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field.

Selection criteria

Double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure.

Data collection and analysis

Two authors independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model.

Main results

We included 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001.

Authors' conclusions

The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.

 

Plain language summary

Diuretics for heart failure in adults

Chronic heart failure (CHF) (also called congestive heart failure, cardiac failure and heart failure) is a disorder in which the heart loses its ability to pump blood efficiently throughout the body. The oxygen and nutrients in the blood provide the body with the energy it needs to operate efficiently. Chronic heart failure causes breathlessness and fatigue because the heart cannot function as it should. Heart failure may affect the left, right, or both sides of the heart. If the left half of the heart fails (left ventricular failure), fluid will build up in the lungs due to congestion of the veins of the lungs. If the right half of the heart fails (right ventricular failure), general body vein pressure will increase and fluid will accumulate in the body, especially the tissues of the legs and abdominal organs (of these, the liver is the organ most likely to be affected). Often left heart failure leads to right heart failure causing biventricular failure (both sides). Fluid may build up in the lungs and legs. Coronary artery disease, a heart attack, or high blood pressure are some of the causes of heart failure. Drug treatments include digitalis, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretics. Diuretics are important as they relieve symptoms quickly and control fluid retention. Possible side effects with diuretics include heart irregularities (arrhythmias), low blood pressure and disturbed kidney function. Some of the diuretics used are furosemide, bumetanide and chlorothiazide. The available data from several small controlled trials show that in patients with CHF, conventional diuretics appear to reduce the risk of death and worsening heart failure when compared to an inactive sugar pill (placebo). About 80 deaths may be avoided for every 1000 people treated. Diuretics also increase the ability to exercise, by about 28% to 33% more than with other active drugs. These conclusions were based on 14 controlled trials (525 people), of which three trials noted deaths in 202 people randomised to receive either diuretic or placebo, and two trials, a total of 169 people, looked at hospitalisation for worsening heart failure. Of the seven trials comparing diuretic treatment with another drug, the effects on exercise were studied in four trials where 91 people were randomised to receive either a diuretic or an ACE inhibitor or digoxin. Most of the trials had small numbers and lasted from 4 to 24 weeks, a short time for a chronic disease. The age of the participants was 59 years, which is relatively young, and the use of diuretic drug was not standardised across the studies. More research would be needed to further confirm the long term benefits of diuretic treatment for CHF patients because these studies were small.

 

摘要

背景

利尿劑治療心衰竭

慢性心衰竭，在全世界來說，是死亡及罹病的一個主要原因。利尿劑因為能夠緩解心衰竭症狀而被認為是治療心衰竭的第一線用藥。然而，利尿劑對於心衰竭的存活率及遏止其惡化的效果，則是不確定的。

目標

評估使用利尿劑治療心衰竭的益處與壞處

搜尋策略

查閱以下幾個資料庫:Cochrane Central Register of Controlled Trials (Issue 2 2004), MEDLINE 1966 – 2004, EMBASE 1980 – 2004 及 HERDIN database題材相關的期刊及所引用的論文均予以詳細的審查。我們也聯繫相關廠商及研究人員。

選擇標準

符合條件的文獻，必須是雙盲隨機試驗，比較一種利尿劑和安慰劑或是比較一種利尿劑與其他治療心衰竭的有效藥物(如ACE抑制劑,毛地黃)在慢性心臟衰竭病患的治療成效。

資料收集與分析

二個評論者各自獨立提取資料併評估每個研究符合條件的程度及其研究方法的品質。提取的資料輸入了Review Manager 4.2 computer 軟體,比較治療組與對照組兩組二分變項資料間的勝算比, 連續性資料的平均值的差異。研究群體的異質性則由Chisquare test估計。如果沒有證據顯示有統計上的異質性, 且臨床上資料彙整是適當的,將以fixedeffect model分析,取得一個合併估計值。

主要結論

共包括14 個試驗(525 個參與者), 7 個試驗是以安慰劑為對照組的, 另7 個試驗則是比較利尿藥與其它替代藥物,譬如ACE 抑制劑及Digoxin。我們分析病患死亡率及心衰竭的惡化。死亡率的資料由3 組以安慰劑為對照組的試驗中(202 個參與者)中加以分析。以利尿劑治療的受試者的死亡率低比以安慰劑治療者低。勝算比(ＯＲ)0.24, 95%信賴區間(CI) 0.07 到0.83; P = 0.02 。有2個試驗中,服用利尿劑者因為心衰竭惡化而入院的減少(169 個參與者), 勝算比 0.07 (95% CI 0.01 到0.52; P = 0.01) 。在其他4個比較利尿劑與其他控制心衰竭藥物的試驗中(91 個參與者),利尿藥可以改善心衰竭病患的運動耐受性, 平均WMD差異為 0.72, 95% CI 0.40 到1.04; P < 0.0001。

作者結論

從現有的的小規模試驗分析中顯示，慢性心臟衰竭的病患，使用傳統的利尿劑療法比使用安慰劑療法的病人，較能減低死亡率和心衰竭的惡化。若是和其他治療心衰竭的用藥相比，利尿劑在改善病患運動耐受性的效果較佳。

翻譯人

本摘要由臺北榮民總醫院藍鴻杰翻譯。

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

總結

利尿藥治療成人心衰竭。慢性心衰竭(CHF) (又叫做鬱血性心衰竭, 心臟衰竭和心衰竭)是心臟失去把血液有效率地輸送到全身的能力。氧氣和營養在血液中提供身體所需的能量讓它能夠有效率地運作著。慢性心衰竭會因為心臟並不能夠正常的運作而有氣促和疲勞的症狀。心衰竭可能影響左心,右心, 或是同時影響兩側。左半邊心衰竭發生時(左心室衰竭), 由於肺靜脈血液的鬱積,液體將囤積在肺葉中 。如果右半邊心衰竭(右心室衰竭), 全體循環靜脈壓力將增加且液體將積累在身體、特別是腿部和腹部器官(其中, 肝臟是最容易受影響的一個)。左心力衰竭經常引起右心衰竭導致雙心室衰竭(雙側)。液體可以囤積在肺和腿。冠狀動脈病、心臟病發作, 或高血壓是一些引起心衰竭的原因。藥物治療包括Digitalis、ACE抑制劑、乙型阻斷劑和利尿藥。利尿劑很重要因為他們能夠迅速緩解症狀與控制液體囤積。 利尿劑可能的副作用為心跳不規律 (心律不整)、低血壓、以及妨礙腎臟功能。某一些使用的利尿劑為furosemide、bumetanide以及chlorothiazide。傳統的利尿劑與無作用的糖果(安慰劑)相比，似乎可以減少死亡與心衰竭惡化的風險，其中大約每1000人，即可以避免80人死亡。利尿劑也可促進運動能力，與其他有效藥相比，大約多出28%∼33%。 這些結論乃根據14個控制試驗(525 個人),其中的3個試驗提到202個受試者,隨機接受利利尿或安慰劑後的死亡人數, 另外2個試驗,計169 個人,提到因為心衰竭惡化而須要住院治療的比率。另外的7個試驗比較利尿劑與其它藥物, 有4個試驗是做對運動耐受度的影響,共有91 個人隨機接受利尿劑或ACE抑制劑或Digoxin 。大多的試驗為小規模試驗,持續時間從4周到24周,對慢性疾病而言時間有點短。參加者的年齡是59,是相對地年輕且利尿藥物的用法在這些試驗中並未被標準化。