Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema

Harikrishna Makani, Sripal Bangalore, Jorge E. Romero, Omar Wever-Pinzon, Franz H. Messerli

Research output: Contribution to journalArticle

88 Citations (Scopus)

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). Conclusion 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.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalAmerican Journal of Medicine
Volume124
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Calcium Channel Blockers
Renin-Angiotensin System
Edema
Angiotensin-Converting Enzyme Inhibitors
Confidence Intervals
Incidence
Randomized Controlled Trials
Hypertension
MEDLINE
Sample Size

Keywords

  • ACE inhibitors
  • Aliskiren
  • ARBs
  • Calcium channel blockers
  • Hypertension
  • Meta-analysis
  • Peripheral edema

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. / Makani, Harikrishna; Bangalore, Sripal; Romero, Jorge E.; Wever-Pinzon, Omar; Messerli, Franz H.

In: American Journal of Medicine, Vol. 124, No. 2, 02.2011, p. 128-135.

Research output: Contribution to journalArticle

Makani, Harikrishna ; Bangalore, Sripal ; Romero, Jorge E. ; Wever-Pinzon, Omar ; Messerli, Franz H. / Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. In: American Journal of Medicine. 2011 ; Vol. 124, No. 2. pp. 128-135.
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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). Conclusion 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.",
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AB - 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). Conclusion 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.

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