title: Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema.
abstract: BACKGROUND
  Peripheral edema is a common adverse effect of calcium channel blockers. The addition of a renin-angiotensin system blocker, either an angiotensin-converting enzyme inhibitor or an ARB, has been shown to reduce peripheral edema in a dose-dependent way.
  
  
  METHODS
  We performed a MEDLINE/COCHRANE search for all prospective randomized controlled trials in patients with hypertension, comparing calcium channel blocker monotherapy with calcium channel blocker/renin-angiotensin system blocker combination from 1980 to the present. Trials 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.
  
  
  RESULTS
  We analyzed 25 randomized controlled trials with 17,206 patients (mean age 56 years, 55% were men) and a mean duration of 9.2 weeks. The incidence of peripheral edema with calcium channel blocker/renin-angiotensin system blocker combination was 38% lower than that with calcium channel blocker monotherapy (P<.00001) (relative risk [RR] 0.62; 95% confidence interval [CI], 0.53-0.74). Similarly, the risk of withdrawal due to peripheral edema was 62% lower with calcium channel blocker/renin-angiotensin system blocker combination compared with calcium channel blocker monotherapy (P=.002) (RR 0.38; 95% CI, 0.22-0.66). ACE inhibitors were significantly more efficacious than ARBs in reducing the incidence of peripheral edema (P<.0001) (ratio of RR 0.74; 95% CI, 0.64-0.84) (indirect comparison).
  
  
  CONCLUSIONS
  In patients with hypertension, the calcium channel blocker/renin-angiotensin system blocker combination reduces the risk of calcium channel blocker-associated peripheral edema when compared with calcium channel blocker monotherapy. ACE inhibitor seems to be more efficacious than ARB in reducing calcium channel blocker-associated peripheral edema, but head-to-head comparison studies are needed to prove this.
authors.affiliation: St Luke's Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, NY 10019, USA.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Makani
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.forename: Jorge
authors.initials: J
authors.lastname: Romero
authors.forename: Omar
authors.initials: O
authors.lastname: Wever-Pinzon
authors.forename: Franz H
authors.initials: FH
authors.lastname: Messerli
mesh_terms: D000577:Amides / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced* / Q000517:prevention & control*; D005260:Female; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012107:Research Design; D016312:Treatment Refusal; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren