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

Objective. Most patients with systemic sclerosis (SSc) have Raynaud's pheno menon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for th e treatment of RP in SSc. The primary outcome measures were frequency and s everity of ischemic attacks, digital skin temperature, patient and physicia n global assessments, and digital ulcers. Methods. The Cochrane search strategy was used to ascertain all trials in a ll languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion cri teria were randomized controlled trials of >2 days' duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized contro lled trials were eligible for inclusion. The total number of patients inclu ded 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 lac k of a control group (1 trial). Data were abstracted independently by 2 rev iewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, infor mation 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% confidenc e interval [95% Cl] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respe ctively. 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 seve ral small clinical trials and appear to lead to significant clinical improv ement in both the frequency and the severity of ischemic attacks. Most tria ls were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy o f calcium-channel blockers in reducing the severity and frequency of ischem ic 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, randomize d controlled trial needs to be conducted.