Clinical research studyEffect of Renin-Angiotensin System Blockade on Calcium Channel Blocker-Associated Peripheral Edema
Section snippets
Search Strategy
Trials were searched in PubMed and the Cochrane Central Register of Clinical Trials (Cochrane Library Issue 2, 2009) using the key terms “calcium channel blockers” OR “calcium antagonists” OR “CCBs” OR using the names of individual calcium channel blockers. We restricted our search to randomized controlled trials in human beings and in peer-reviewed journals from 1980 to March 2010. No language restriction was applied. We checked the reference lists of the reviewed articles and original studies
Study Selection and Patient Characteristics
We identified 36 trials comparing calcium channel blocker monotherapy with calcium channel blocker combination with renin-angiotensin system blockers, of which 25 met the inclusion criteria16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 (Figure 1). The 25 trials enrolled 17,206 patients (55% ± 9% were male) with a mean age of 56 ± 5 years who were followed up for 9.2 ± 3 weeks. Of these, 15 trials with 9437 patients compared calcium channel blocker
Discussion
The present study compared the incidence of peripheral edema and the withdrawal of patients because of peripheral edema with calcium channel blocker monotherapy and with calcium channel blocker/renin-angiotensin system blocker combination. Both incidence and withdrawal rates were significantly lower with calcium channel blocker/renin-angiotensin system blocker combination compared with calcium channel blocker monotherapy at similar doses of the calcium channel blocker in both arms. ACE
Study Limitations
As with other meta-analyses, given the lack of data in each trial, we did not adjust our analysis for adherence to therapy. Also, the results are subject to limitations inherent to any meta-analysis based on pooling of data from different trials with different duration, different definitions for peripheral edema, and different patient groups. We did not assess the antihypertensive efficacy of all groups because this meta-analysis was mainly performed to compare the safety of the combination
Conclusions
The combination of ACE inhibitors or ARBs with calcium channel blockers reduces calcium channel blocker-associated peripheral edema. ACE inhibitors seem to be more efficacious than ARBs in reducing calcium channel blocker-associated peripheral edema (based on indirect comparison), but further head-to-head studies are needed to conclusively test this association.
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Funding: None.
Conflict of Interest: HM, SB, JR, OW-P: none. FHM.: Ad hoc consultant/speaker for the following organizations: Novartis, Boehringer Ingelheim, Forest, Daiichi Sankyo, Sanofi, and Savient Pharmaceuticals. Grant support from GSK, Novartis, Forest, Daiichi Sankyo, and Boehringer Ingelheim. None of the authors received any compensation for their work on this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.