1. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema Makani H et al. Am J Med. 2011;124:128-135, METHOD: A MEDLINE/COCHRANE search for randomised controlled trials (RCT) in patients with hypertension, comparing calcium channel blocker (CCB) monotherapy with CCB/renin angiotensin system blocker combination conducted from 1980. RCTs reporting the incidence of peripheral edema or withdrawal of patients because of edema and total sample size more than 100 were included in this analysis. 25 RCTs with 17,206 patients (mean age 56 years, 55% were men) and a mean duration of 9.2 weeks..

2. Combining RAAS inhibitors with CCB decreases edema incidence/withdrawal rates with CCB CCB = calcium channel blocker; RAS = renin-angiotensin system *p<0.0001 Makani H et al. Am J Med. 2011;124:128-135 Percentage

3. ACE inhibitors are more efficacious than ARBs in reducing CCB-associated edema Makani H et al. Am J Med. 2011;124:128-135 P<0.00001 P=0.0001

4. Clinical significance The combination of RAAS inhibitors with calcium channel blockers (CCB) reduces the incidence by 38% and withdrawal rate due to peripheral edema by 62% when compared with calcium channel blocker monotherapy. ACE inhibitors were significantly more efficacious than ARBs in reducing the incidence of CCB-associated peripheral edema by 54% and 24%, respectively (P<0.0001), Aliskiren did not show significant reduction of CCB-associated cough. Makani H et al. Am J Med. 2011;124:128-135.