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.

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.

Read the full abstract...

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. This is an update of a review first published in 2008.


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

Search strategy: 

For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 May 2012), CENTRAL (Issue 4, 2012) and clinical trials databases. We contacted one pharmaceutical company and one trial author for additional information. In addition, the reference lists of relevant studies were searched for additional citations. 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: 

Two members of the review team independently assessed the trials for inclusion and their quality and extracted the data. 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.