Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis

Background. To determine the efficacy of calcium channel blockers (CCBs) for primary Raynaud's phenomenon (RP). Primary outcomes were frequency and severity of RP attacks. Methods. A meta-analysis was conducted using primary data sources: Medline, Current Contents and the Cochrane Controlled Trials Register. Inclusion criteria were randomized controlled trials (RCTs) of >2 days' duration with <35% dropouts. Eighteen of 31 trials were eligible for inclusion [13 nifedipine vs placebo; five other CCBs vs placebo (n = 361)]. The main reasons for trial exclusion were: subset data (primary RP) not provided (n = 10); data published more than once (n = 1); lack of control group (n = 1); and lack of randomization (n = 1). Data were abstracted independently and a weighted mean difference (WMD) was calculated for the outcomes. Results. The WMD (95% confidence interval) of all CCBs vs placebo for reduction in the frequency of attacks (n = 17) over 1 week was -5.00 (-9.02, -0.99) (P = 0.01) or -2.80 (-3.90, -1.70) when heterogeneity was considered, and -6.05 (-11.19,-0.19) (P = 0.04) for nifedipine alone (n = 10). The WMD of all CCBs vs placebo (n = 8) for reduction in severity of attacks (assessed with a 10-cm visual analogue scale) was -1.39 (-2.20, -0.58) (P = 0.0007) and -1.81 (-3.08, -0.54) (P = 0.005) for nifedipine alone (n = 5). Conclusions. Several small RCTs of CCBs for primary RP have been conducted and have yielded clinical improvement in the frequency and severity of ischaemic attacks. Most trials were crossover trials in which order effect was not studied; this may have introduced bias. The effect size may have been small because of low dosing in studies. The efficacy of CCBs for reducing severity and frequency of ischaemic attacks in primary RP is small (average of 2.8 to 5.0 fewer attacks per week and a 33% reduction in severity).