Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis

Arthritis Rheum. 2001 Aug;44(8):1841-7. doi: 10.1002/1529-0131(200108)44:8<1841::AID-ART322>3.0.CO;2-8.


Objective: Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for the treatment of RP in SSc. The primary outcome measures were frequency and severity of ischemic attacks, digital skin temperature, patient and physician global assessments, and digital ulcers.

Methods: The Cochrane search strategy was used to ascertain all trials in all languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion criteria were randomized controlled trials of >2 days' duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized controlled trials were eligible for inclusion. The total number of patients included was small (n = 109). Most trials included primary and secondary RP, and the main reasons for trial exclusion were inability to extract subset data on SSc patients (18 trials), data published previously (2 trials), and lack of a control group (1 trial). Data were abstracted independently by 2 reviewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, information was not available for all outcomes within trials.

Results: The WMD of all calcium-channel blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5 trials) for the reduction in the frequency of ischemic attacks over a 2-week period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and -0.99 (95% CI -1.74, -0.24), respectively.

Conclusion: Calcium-channel blockers for RP in SSc have been tested in several small clinical trials and appear to lead to significant clinical improvement in both the frequency and the severity of ischemic attacks. Most trials were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy of calcium-channel blockers in reducing the severity and frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, randomized controlled trial needs to be conducted.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Calcium Channel Blockers / therapeutic use*
  • Cross-Over Studies
  • Humans
  • Iloprost / administration & dosage
  • Iloprost / therapeutic use
  • Injections, Intravenous
  • Ischemia / prevention & control
  • Losartan / therapeutic use
  • Randomized Controlled Trials as Topic
  • Raynaud Disease / complications
  • Raynaud Disease / drug therapy*
  • Scleroderma, Systemic / complications*
  • Skin Temperature / drug effects
  • Skin Ulcer / drug therapy


  • Calcium Channel Blockers
  • Iloprost
  • Losartan