A Journal Article Based Approach to Understanding the Clinical Aspects of Hypertension
Volume 1 Issue 10
May  2016  
Context and Study Objective
Calcium channel antagonists (CCBs) are widely used anti-hypertensives but peripheral edema frequently limits up-titration to full therapeutic doses. While the primary endpoint of this study was the anti-hypertensive efficacy of combination CCB/angiotensin converting enzyme inhibitor (ACEi) therapy versus each as mono-therapy, a secondary endpoint was the incidence of CCB related edema.

Design, Setting, and Participants
In a placebo controlled, double blind fashion, patients were randomized to varying doses of felodipine, enalapril, combination therapy, or placebo for 8 weeks. Peripheral edema was only recorded if volunteered by the patient. Those with heart failure, liver disease, or chronic kidney disease were excluded. 
Results
-700 participants were included with a mean age of 54. Baseline BP was 155/102 mm Hg.       
-The incidence of felodipine induced edema was dose dependent, with a mean rate of 11% when low, medium, and high dose therapy were considered in aggregate.  Rates of edema by CCB dose were not reported. 
-Among those on combination CCB/ACEi therapy, edema was reported in 4.1% of subjects when all study arms were included.
Clinical Perspective
-This study underestimates the incidence of CCB related edema as self-report rather than active surveillance was employed. Other studies indicate rates as high as 25% on full dose therapy.
-Mechanistically, it's believed that CCB associated edema is not related to fluid retention but is a redistributive phenomenon. Given that CCBs cause arteriolar dilatation, there is enhanced transmission of systemic pressure to the level of the capillary thereby creating a pressure gradient favoring the extravasation of fluid from the vascular space to the interstitium. Since ACEi therapy causes venodilation, the transcapillary pressure gradient is reduced and extravascular fluid leak is minimized.  This theory also explains why CCB edema is less diuretic responsive. 
-As this article suggests, I pair higher CCB doses with an ACEi/ARB in order to minimize edema. Not withstanding insurance limitations, combination tablets  (Lotrel, Azor) are available. 
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