The quality of evidence is downgraded by inconsistency (statistical heterogeneity).
A Cochrane review [Abstract] 1 included 7 studies with a total of 296 subjects with primary Raynaud's phenomenon. Four studies examined nifedipine and 3 investigated nicardipine for primary Raynaud's phenomenon. Oral calcium channel blockers (CCBs) decreased the frequency of attacks (SMD 0.23, 95% CI 0.08 to 0.38; 7 studies, n=358) compared with placebo. This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on CCBs compared to placebo. Nifedipine studies showed a decrease in the frequency of attacks (SMD 0.32, 95% CI 0.10 to 0.54; 4 studies, n=206) translating to 2.41 (95% CI 0.75 to 4.06) fewer attacks per week on nifedipine compared to placebo. Treatment with CCBs appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling).
Another meta-analysis 2 included 18 studies with a total of 437 subjects with primary Raynaud's phenomenon; 13 studies compared nifedipine vs. placebo, and 5 compared other CCBs vs. placebo. Meta-analysis (17 studies, n=348) showed that CCBs compared with placebo provided a significant reduction in the frequency of ischaemic attacks over a 1-week period, with a WMD of -5.00 (95% CI -9.02 to -0.99), which means a reduction of about five attacks in a 1-week period. The WMD of all CCBs vs. placebo (8 studies, n=147) for reduction in severity of attacks (assessed with a 10-cm visual analogue scale) was -1.39 (95% CI -2.20 to -0.58). With an average mean severity in the placebo group of 4.25, this can be thought of as a 33% reduction in the severity of attacks. Nifedipine reduced the frequency of attacks (WMD -6.05, 95% CI -11.19 to -0.19) and the severity of attacks on a 10-cm visual analogue scale (WMD -1.81, 95% CI -3.08 to -0.54) compared with placebo.
Another Cochrane review [Abstract]3 included 38 studies (33 cross-over RCTs) with a total of 982 subjects. Nine studies (n=365) included patients with primary Raynaud's phenomenon, 5 (n=63) patients with secondary Raynaud's phenomenon, and the rest included a mixture of patients with primary and secondary Raynaud's phenomenon (n=554). Twenty-two studies compared nifedipine versus placebo, 6 nicardipine versus placebo, 2 nisoldipine versus placebo, 3 diltiazem versus placebo, and individual studies compared Bay K 9320, amlodipine, isradipine, or verapamil versus placebo. Calcium channel blockers (CCBs) reduced the average number of attacks per week compared to placebo (WMD -6.13, 95% CI -6.60 to -5.67; statistical heterogeneity I²=98%; 23 studies, n=528). The average duration of attacks did not differ between CCBs and placebo (6 studies, n=69). Measured on a 10-cm visual analogue scale, CCBs reduced attack severity by 0.62 cm (95% CI -0.72 to - 0.51; statistical heterogeneity I²=92%; 16 studies, n=415) and average pain per attack (WMD -1.47 cm, 95% CI -2.21 to -0.74; statistical heterogeneity I²=72%; 4 studies, n=62). Subgroup analyses by Raynaud's type, CCB class, and CCB dose suggested that dihydropyridine CCBs in higher doses were more effective for primary Raynaud's than for secondary Raynaud's, and CCBs had a greater effect in primary than in secondary Raynaud's. No difference in withdrawals from studies due to adverse effects (RR 1.30, 95% CI 0.51 to 3.33; 2 studies, n= 63) was observed. The most common side effects were headache, dizziness, nausea, palpitations, and ankle edema. No serious adverse events (death or hospitalization) were reported.
The following decision support rules contain links to this evidence summary:
Primary/Secondary Keywords