Peripheral edema is a common, dose-dependent adverse effect of dihydropyridine calcium channel blockers (CCBs) and is seen in approximately 5%-10% of patients. It is thought to result from preferential arterial dilation, which increases the pressure gradient between the capillaries and interstitium, leading to extravasation of intravascular fluid.
Combining renin-angiotensin system blockers with CCBs has been shown to reduce the risk of peripheral edema by promoting venule dilation and therefore decreasing the pressure gradient between the capillaries and interstitium. In addition, the ACCOMPLISH trial showed that dual therapy with an ACE inhibitor and a CCB was superior to ACE inhibitor plus thiazide diuretic in reducing cardiovascular events. As a result, the combination of an ACE inhibitor and a CCB is advocated for patients in whom the need for dual therapy is likely.