Oral vasodilators for primary Raynaud's phenomenon

 

Abstract

Background

Many different drugs have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered the drugs of choice, the evidence of the effects of alternative pharmacological treatments is limited.

Objectives

To assess the effects of various drugs with vasodilator actions on primary Raynaud's phenomenon.

Search methods

The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 24 July 2007), and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 3, 2007). In addition, we searched MEDLINE (January 1966 to July 2007), EMBASE (1980 to July 2007) and reference lists of relevant articles. We contacted pharmaceutical companies. There were no language restrictions.

Selection criteria

Randomised controlled trials evaluating the effects of oral formulations of any drug with vasodilator effects on subjective symptoms in primary Raynaud's phenomenon. Treatment with, or comparison with, calcium channel blockers was not assessed in this review.

Data collection and analysis

Both authors assessed the trials for inclusion and their quality. One author (BV) extracted the data MS checked the results. Data extraction included adverse events. we contacted trial authors for missing data.

Main results

Eight studies involving 290 participants were included. Two trials examined the effects of captopril, the rest were single trials on single drugs. All comparisons were with placebo. The methodological quality of most trials was poor.

Enalapril was associated with a small increase in the frequency of attacks per week (difference in means 0.8; 95% CI 0.43 to 1.17). The difference between the intervention groups on a subjective improvement score was non-significant.
There was a significant effect of buflomedil on the frequency of attacks per week (weighted mean difference (WMD) -8.8; 95% CI -17.55 to -0.09), but there was no evidence of effect on the severity score.
The proportion with fewer attacks was significantly higher on moxisylyte than on placebo (relative risk (RR) 4.33; 95% CI 1.36 to 13.81).
For captopril, beraprost, dazoxiben and ketanserin there was no evidence of an effect on the frequency, severity or duration of attacks.
Beraprost and moxisylyte gave significantly more adverse effects than placebo.

Authors' conclusions

Poor methodological quality, small sample sizes and the limited data available resulted in low precision of the statistical results and limited value of the overall results .The overall results show that there is no evidence for an effect of vasodilator drugs on primary Raynaud's phenomenon.

 

Plain language summary

Oral vasodilator drugs to reduce the symptoms of primary Raynaud's phenomenon

Raynaud's phenomenon is caused by short term constriction of the small arteries in the extremities, usually the fingers. For a few minutes, usually, the fingertips go white and feel numb or tingle and prickle. Then the blood flow returns and they become warm and red, which can also be painful. For some people the toes, ears, nose, tongue or nipples are affected. Cold or emotional stress can trigger the attacks. Keeping warm, stopping smoking and avoiding using tools that vibrate can prevent attacks but sometimes drug therapy is needed. Calcium channel blockers such as nifedipine are the drugs of choice but can have unwanted side effects.

The review looked at the effectiveness of other drugs that can be taken by mouth. These were drugs that increase blood flow (vasodilators). The evidence from randomised controlled trials is limited. The review authors identified eight controlled studies. These were published between 1980 and 1996 and involved a total of 290 participants randomly assigned to the vasodilator drug or placebo. The length of treatment varied from two weeks to six months. Only two trials looked at the same drug, the angiotensin converting enzyme (ACE) inhibitor captopril so most of the findings were from single trials. Taking enalapril resulted in a small increase in the frequency of attacks in a week. Buflomedil reduced the frequency of attacks but without a clear effect on their severity. Moxisylyte (thymoxamine) also reduced attacks but both beraprost and moxisylyte produced more adverse effects than with placebo. For captopril, beraprost, dazoxiben and ketanserin there was no evidence of an effect on the frequency, severity or duration of attacks.

The methodological quality of most trials was poor and they were small. The outcomes were subjective and were reported on scales that were not well described or validated. This makes the clinical importance of the results difficult to assess, especially if the placebo response is high.

 

摘要

背景

口服血管擴張劑(vasodilators)用於原發性雷諾氏現象(primary Raynaud's phenomenon)

許多不同種類的藥物被建議用於症狀治療原發性雷諾氏現象，除了作為首選用藥的鈣離子阻斷劑(calcium channel blockers)之外，其他取代性的藥物的使用則缺乏充分有效的証據。

目標

評估數種血管擴張藥物用於治療原發性雷諾氏現象的效果

搜尋策略

考科藍周邊血管疾病小組搜尋了The Cochrane Specialized Register (最新資料為2007年7月24日)和the Cochrane Central Register of Controlled Trials (CENTRAL) (最新資料 Issue 3, 2007)。此外我們搜尋了MEDLINE (1966年1月至2007年7月)， EMBASE (1980年至2007年7月) 以及相關文獻的引用來源，我們和藥廠取得聯繫以取得所有可提供的資訊包括已發表或未發表的試驗，在文獻搜尋時並無語言限制。

選擇標準

隨機臨床試驗(RCTs)評估任何口服血管擴張藥物對原發性雷諾氏現象的療效，在這篇回溯研究中並未討論鈣離子阻斷劑的使用。

資料收集與分析

兩位作者皆對文獻的可收錄性與品質進行評價，其中一位作者(BV)取擷資料而另一位(MS)檢驗之，擷取的資料包括副作用，遺漏的資料我們和文獻的作者聯繫取得。

主要結論

共收入了8篇研究包含290位受試者，其中有兩篇針對Captopril進行研究，其餘的則各針對單一種不同的藥物作研究，所有的文獻皆以安慰劑作為對照組，大部分研究方法的品質都不佳。 研究顯示Enalapril少量增加每星期發作的頻率(difference in means 0.8; 95% CI 0.43 to 1.17)，但在主觀的改善計分(improvement score)上兩組並無顯著差異。 Buflomedil對降低每周的發作頻率有顯著的效果(weighted mean difference (WMD) −8.8; 95% CI −17.55 to −0.09)，但對於症狀嚴重度計分(severity score)並無顯著的效果。 而使用moxisylyte治療和安慰劑相比，較少發作病患的比例顯著的較高(relative risk (RR) 4.33; 95% CI 1.36 to 13.81) 至於Captopril, beraprost, dazoxiben和ketanserin則無證據支持對降低發作的頻率、嚴重度或持續時間有效。此外beraprost和moxisylyte與安慰劑相比有較多副作用的產生。

作者結論

研究方法品質不佳，較少的樣本數與研究數據資料取得受限影響了統計分析結果的精確性也影響了整體結果的份量，整體來說目前沒有證據支持血管擴張藥物對原發性雷諾氏現象具有療效。

翻譯人

本摘要由臺中榮民總醫院吳慧中翻譯。

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

總結

口服血管擴張劑用於降低原發性雷諾氏現象之症狀 雷諾氏現象乃肇因於四肢小動脈的短暫收縮，通常見於上肢手指，通常指頭會變的蒼白並且感覺麻木或是抽、刺痛持續約數分鐘的時間。之後血流回復，指頭變的暖且充血潮紅，此時也會有疼痛感，某些病人的患部可能是腳趾，耳朵、鼻子、舌頭或乳頭。寒冷或情緒壓力能夠引發此現象的發作，而保暖、戒菸以及必免使用會引起震動的工具能預防發作，但有時使用藥物治療是必要的。首選藥物為鈣離子阻斷劑，例如nifedipine，但會有併發的副作用，本篇回顧研究其他種類口服血管擴張劑的效果，由這幾篇隨機臨床試驗(RCTs)得到的證據力是有限的，作者搜尋到8篇對照研究，分別發表於1980年至1996年間，總共包含290位隨機分派的受試者，治療周期由兩周至六個月不等，其中有兩篇同樣針對 angiotensin converting enzyme (ACE) inhibitor captopril作研究。使用enalapril一周後能略降發作的頻率，而Buflomedil能降低發作頻率但對症狀的嚴重程度無明顯改善，Moxisylyte(thymoxamine)也能降低發作率，但Beraprost和moxisylyte兩種藥物都比安慰劑引起較多的副作用，沒有證據指出captopril, beraprost, dazoxiben 和ketanserin對降低發作率、嚴重度及持續時間有效。大部分的試驗的研究方式不佳、樣本數太少，對病患臨床反應的觀察太主觀，對症狀的嚴重分級並未描述或驗證，這使得臨床結果難以評估，尤其是當安慰劑效果又很強的時候。