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Clinical Perspective
-I pair amlodipine with an ACEi or angiotensin receptor blocker (ARB). While more evidence exists for the addition of an ACEi, I favor ARBs as the incidence of cough is markedly lower. Low-dose combination therapy reduces side-effect burden; both amlodipine-olmesartan and amlodipine-benazepril combination tablets are available.
-More broadly, edema should not be an indication for CCB withdrawl. Since edema is dose-dependent, lowering the dose is effective. Third generation agents such as amlodipine or non-dihydropyridine CCBs such as diltiazem and verapamil are also less edema-genic than 2nd generation agents like nifedipine and felodipine. Since the edema is not related to volume retention, diuretics are of little benefit.
-Mechanistically, CCB-associated edema is not the result of fluid retention. Rather, CCBs decrease arteriolar resistance which increases the arteriolar-venous pressure gradient at the level of the capillary. This change in hydrostatic forces favors the extravasation of fluid from the vascular to the interstitial space. Because ACEi therapy promotes venodilatation, the transcapillary pressure gradient is normalized and extravascular fluid leak is minimized.
-Study Criticism: this paper 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.
-Disclosures: I have no conflicts to declare.
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