Calcium Channel Blocker-Related Peripheral Edema: Can It Be Resolved?

Domenic A. Sica, MD

Disclosures
In This Article

Treatment of CCB-Related Edema

There have been inconsistent findings when switching from one dihydropyridine CCB to another or when switching to different formulations of the same drug to lessen or resolve peripheral edema.[29,30,31] Edema will diminish upon conversion from a dihydropyridine CCB to a nondihydropyridine CCB such as verapamil or diltiazem. In addition, the newer, third-generation dihydropyridine CCBs such as lacidipine,[32,33] manidipine,[34] and lercanidipine[32,33,34,35] are regularly reported to cause less peripheral edema. Also, there is some suggestion that nocturnally administered CCBs carry a reduced risk of edema development.[36,37] Diuretic therapy has been offered as one mode of treatment for CCB-related peripheral edema despite the fact that this form of peripheral edema is not related to volume overload per se. When carefully studied, some change in limb volume, a more precise marker of CCB-related vasodilation effect, can be demonstrated with thiazide-type diuretics.[26] However, the manner by which diuretic therapy improves CCB-related peripheral edema may not be physiologically correct. It is ill advised to routinely diurese patients with CCB-related peripheral edema for the sole purpose of correcting the edema state.

Another strategy useful for the resolution of CCB-related edema is providing a venodilator drug as a means to reducing the venous hypertension that characterizes this phenomenon.[13,37,38,39] Several drug classes have relevant venodilating potential and, in addition, can further reduce blood pressure. This includes ACE inhibitors, ARBs, and nitrates.[40] ACE inhibitors have been the best studied of this group. They have been shown in several trials to improve edema rate and severity when administered to patients with edema from CCBs.[38,39] However, several questions still remain: What is the optimal venodilating dose of an ACE inhibitor for a specific CCB?, and, Do intraclass differences exist among the several ACE inhibitors? Until such information becomes available, ACE inhibitors should be empirically dosed according to blood pressure considerations and any venodilating effect accepted as a secondary benefit. It should also be appreciated that addition of an ACE inhibitor to a CCB further reduces blood pressure and may permit reduction in the dose of the CCB. This will also aid in resolution of the peripheral edema.

ARBs should behave similarly to ACE inhibitors. However, limited information is available in the published literature to allow substantiation of this hypothesis. Nitrates offer some venodilating potential but require a stop-start regimen to forestall nitrate tolerance. Thus, the dosing regimen becomes fairly complicated if their use is contemplated as a means to modifying the peripheral edema seen with CCB.

Peripheral edema is probably the most troubling side effect of CCB therapy. The mechanisms of its development are understandable, so treatment strategies can be developed. A prospective evaluation of treatment strategies has not been undertaken. An approach to peripheral edema that empirically employs dose reduction, interclass shifting of medication, and/or ACE inhibitor or ARB therapy is quite reasonable. Failing conventional treatment, discontinuation of the CCB will ultimately resolve the issue.

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