Managing Peripheral Edema in Patients With Arterial Hypertension

Abstract

Calcium channel blockers (CCBs) play a vital role in the management of hypertension. Peripheral edema is the most common side effect reported with CCB monotherapy, especially with high-dose dihydropyridine CCBs. CCB-related peripheral edema is a dose-limiting effect that is usually medically benign but can compromise patient adherence. CCB-related peripheral edema may cause considerable discomfort and patient concern. Patients presenting with peripheral edema should undergo assessment for drug and nondrug causes. Rather than lowering the CCB dose or switching to another monotherapy, combination therapy (e.g, CCB plus a renin-angiotensin-aldosterone system inhibitor) can enhance blood pressure control, generally with lower doses of individual agents, and lessen the risk of adverse events. As recommended by consensus guidelines, addition of a renin-angiotensin-aldosterone system inhibitor as part of combination therapy may accelerate the time to goal blood pressure as well as help alleviate peripheral edema in affected patients. Successful management of CCB-related peripheral edema with lifestyle changes and rational combination therapy is likely to improve blood pressure control and patient outcomes.

Review: A Single-Pill Combination of Telmisartan plus Amlodipine for the Treatment of Hypertension

“…12,14,17 As CCB-induced edema may compromise patient adherence, the ability to reduce the frequency of this side effect may improve compliance, while still providing the BP-lowering benefi ts associated with CCB therapy. 37,38 In summary, the approved single-dose combinations of telmisartan plus amlodipine (40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, and 80 mg/10 mg) demonstrate superior BP-lowering effi cacy than either agent alone and provide high 24-hour BP control rates. These combinations were well tolerated, without increasing the risk for hypotension, and the addition of telmisartan to amlodipine 10 mg was associated with a reduction in the rate of peripheral edema.…”

Amlodipine/Valsartan Single-Pill Combination: A Prospective, Observational Evaluation of the Real-Life Safety and Effectiveness in the Routine Treatment of Hypertension

“…single-dose amlodipine/valsartan combination therapy was associated with lower cardiovascular event costs, with the reported average costs per event and patient from the first year of €2931 and €3770 in the single-pill combination and free-combination groups, respectively.Peripheral edema is a well-known dosedependent and dose-limiting side effect of treatment with CCBs, recognized as a consequence of imbalances involving hydrostatic and oncotic pressure gradients and vascular permeability[30,31]. A recent metaanalysis of CCB-based antihypertensive therapy found that the incidence of, and treatment withdrawal rate for, this toxicity increased with the duration of therapy, with 24% of patients reporting peripheral edema and 5% of patients as well as a 62% reduction in the risk of peripheral edema-related withdrawal (relative risk, 0.38; P<0.01) in a recent meta-analysis[33].…”

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

“…Treatment with amlodipine, a dihydropyridine CCB, is frequently associated with adverse symptoms, that is, flushing, ankle edema, headache and palpitation, caused by drug-induced vasodilation. 33 Although these symptoms usually do not lead to major complications, their presence affects patients' quality of life and leads to a reduction in treatment adherence 34 and relatively high treatment discontinuation rates. In contrast, ARBs are the best-tolerated class of antihypertensive drugs and not only reduce BP without inducing a reflex increase in sympathetic nervous activity (and resulting tachycardia or palpitations) 35 but also, probably through inducing venous vasodilation, diminish the CCB-induced increase in hydrostatic pressure 36 and thereby reduce the frequency of edema.…”