Twenty-five trials (17,206 participants) were included in the review: 15 trials (9,437 participants) compared calcium channel blockers with calcium channel blockers plus an ACE inhibitor; nine trials (7,224 participants) compared calcium channel blockers with calcium channel blockers plus an ARB; one trial (545 participants) compared calcium channel blockers with calcium channel blockers plus aliskiren. Overall study quality was poor. Eight studies were deemed to have a low risk of bias and 17 were considered high risk.
Risk of peripheral oedema: Calcium channel blockers in combination with renin-angiotensin system blockers significantly reduced the risk of peripheral oedema compared with calcium channel blocker monotherapy (RR 0.62, 95% CI 0.53 to 0.74; 25 studies). Subgroup analysis showed significant reduction in risk for calcium channel blockers in combination with ACE inhibitors (RR 0.46, 95% CI 0.37 to 0.58; 15 studies) and with ARBs (RR 0.79, 95% CI 0.64 to 0.97; nine studies). There were no significant differences between groups when compared to aliskiren (one study). Egger's test did not report publication bias (p=0.27). Modest heterogeneity was noted when monotherapy was compared with calcium channel blockers in combination with ARBs; excluding one study resolved this.
Patient withdrawal due to peripheral oedema: Calcium channel blockers in combination with renin-angiotensin system blockers significantly reduced patient withdrawal due to peripheral oedema compared with calcium channel blocker monotherapy (RR 0.38, 95% CI 0.22 to 0.66; seven studies). Subgroup analysis showed significant reduction in withdrawals for calcium channel blockers in combination with ACE inhibitors (RR 0.42, 95% CI 0.22 to 0.80; six studies) and with ARBs (RR 0.27, 95%CI 0.09 to 0.81; one study). Egger's test did not report publication bias (p=0.52). There was no evidence of heterogeneity.