Phosphodiesterase five inhibitors for pulmonary hypertension

 

Abstract

Background

Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary hypertension (SPH). Pulmonary arteriolar vasoconstriction is considered to be an important characteristic of PH. Therapies which aim to vasodilate are used to treat pulmonary hypertension.

Objectives

To determine the clinical efficacy of sildenafil, a vasodilator which works through inhibition of the enzyme phosphodiesterase type V (PDE5I), administered via any route to people with pulmonary hypertension in primary or secondary forms.

Search methods

MEDLINE, EMBASE and CENTRAL were searched with pre-defined search terms. Searches were current as of October 2006.

Selection criteria

Randomised controlled trials were considered for inclusion in the review. We included studies which assessed the effects of sildenafil in participants with PPH and SPH.

Data collection and analysis

Two reviewers independently assessed and extracted data from clinical trials. Data were entered in RevMan Analyses 1.0.2. Continuous data were pooled with an estimate on either WMD (weighted mean difference) or SMD (standardised mean difference) scales. Dichotomous data were pooled and a RR (relative risk) was calculated.

Main results

Four studies recruiting 77 participants met the inclusion criteria of the review. Two studies assessed the acute effects of sildenafil. Two small crossover study assessed the effects of long term administration. The 'acute effect' studies indicated that sildenafil has a pulmonary vasodilatory effect. The two crossover studies showed improvement in symptoms. One study showed improvement in fatigue domains from a validated health status questionnaire. Both crossover studies reported that the drug was well tolerated.

Authors' conclusions

The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.

 

Plain language summary

Phosphodiesterase five inhibitors for pulmonary hypertension

Pulmonary hypertension (PH) is high blood pressure in the lung circulation. It can occur without a known cause, or it can be caused by another lung disease or be secondary to abnormalities in the left side of the heart. The review sought to determine whether there was evidence that sildenafil (also known as Viagra), a drug which opens up the arteries and increases the flow of blood, could decrease pulmonary artery blood pressure and alleviate symptoms of PH. A limited number of studies of short term i duration indicated that the drug can open up the arteries. One small longer-term study found some favourable effects in terms of symptoms, but in the absence of longer term outcomes, we could not establish whether this meant that the people given the drug felt that their levels of daily activity were better. Future studies should be longer in duration, and should measure the impact of treatment on daily activities, mortality, quality of life and exercise capacity.

 

摘要

背景

以Sildeafil治療肺高血壓

肺高血壓(PH)可以是不明原因(原發性肺高血壓﹝PPH﹞)或已知潛在原因(續發性肺高血壓﹝SPH﹞)。肺小動脈血管收縮為認為是PH的一項重要特色。以血管擴張為目標的治療被用作治療肺高血壓。

目標

確認seldenafil，一種經由抑制第五型磷酸二脂?(PDE5I)這種酵素的血管擴張劑，經由任何途徑用於原發性及續發性肺高血壓患者的臨床效益。

搜尋策略

我們以先行訂出的字彙在MEDLINE、EMBASE、CENTRAL進行搜尋。目前搜尋至2005年10月。

選擇標準

本回顧納入隨機對照試驗。我們納入評估PPH及SPH參與者使同sildenafil效用的研究。

資料收集與分析

兩位審查者獨立地評估及自臨床試摘錄數據。數據輸入RevMan Analyses 1.0.2。連續數據被整合來估計加權均數差(WMD)或標準化均數差(SMD)的大小。二分法的數據被整合及計算相對風險(RR)。

主要結論

符合本回顧納入標準的四項研究共有77名參與者。兩項研究評估sildenafil的急性效應。兩項小規模的交叉研究評估長期使用的效果。「急性效應」的研究指出sildenafil具有肺血管擴張的效果。兩項交叉研究顯示症狀改善。一項研究採用有效的健康狀態問卷顯示疲倦領域有改善。兩項交叉研究均顯示藥物的耐受良好。

作者結論

觀察效應的效度因參與者數目偏少及對不同病因的探討不足而受損。長期的效應如NYHA功能分級、症狀、死亡率及運動能力等仍需進一步確認。在sildenafil對臨床重要結果的長期效應能被確立之前，需有更多規模足夠的研究。

翻譯人

本摘要由中國醫藥大學附設醫院陳祖裕翻譯。

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

總結

Sildenafil在短期治療中可降低肺內血壓，但仍需有長期的評估。肺高血壓(PH)是肺循環高血壓。它的發生可以沒有原因，或可因另一種肺病或因心臟左側的異常所引起。本回顧旨在確認是否有證據顯示sildenafil(也稱為Viagra)，一種打開動脈及增加血流的藥物，能否降低肺動脈血壓而改善PH症狀。為數有限的短期研究指出此藥可打開肺動脈。一項小規模的長期研究發現在症狀方面有一些肯定的效應，但由於缺乏長期結果，我們無法確定是否表示人們在用藥後會覺得日常活力的水平會較好。未來的研究應要有較長的期間，且應測量治療對日常活力、死亡率、生活品質及運動能力的影響。