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

Abstract

Calcium channel blocker (CCB)-related edema is quite common in clinical practice and can effectively deter a clinician from continued prescription of these drugs. Its etiology relates to a decrease in arteriolar resistance that goes unmatched in the venous circulation. This disproportionate change in resistance increases hydrostatic pressures in the precapillary circulation and permits fluid shifts into the interstitial compartment. CCB-related edema is more common in women and relates to upright posture, age, and the choice and dose of the CCB. Once present it can be slow to resolve without intervention. A number of strategies exist to treat CCB-related edema, including switching CCB classes, reducing the dosage, and/or adding a known venodilator such as a nitrate, an angiotensin-converting enzyme inhibitor, or an angiotensin-receptor blocker to the treatment regimen. Angiotensin-converting enzyme inhibitors have been best studied in this regard. Diuretics may alter the edema state somewhat, but at the expense of further reducing plasma volume. Traditional measures such as limiting the amount of time that a patient is upright and/or considering use of graduated compression stockings are useful adjunctive therapies. Discontinuing the CCB and switching to an alternative antihypertensive therapy will resolve the edema.

Mitigation of calcium channel blocker-related oedema in hypertension by antagonists of the renin–angiotensin system

“…CCB-induced oedema is caused primarily by the increased capillary hydrostatic pressure that results from greater dilation of pre-capillary than post-capillary vessels. 9,10,12,23 This effect may be mediated, in part, by the greater sensitivity of resistance vessels than capacitance vessels to CCB-induced reductions in myogenic vascular reactivity, 24 and may be augmented by CCB-induced reductions in postural vasoconstriction. 25 Because the oedema is related to the mechanism of action of dihydropyridine CCBs, it represents a class effect.…”

“…10 In contrast, agents that cause post-capillary dilation (for example, ACEIs and ARBs) are ideally suited for the prevention or reversal of CCB-induced oedema because the normalization of intracapillary pressure induced by these agents will reduce fluid extravasation ( Figure 1). 10,12,22 This theoretical concept is borne out by the results of individual clinical trials that have shown that the incidence of oedema is substantially lower in patients who receive ACEI/ CCB or ARB/CCB combination therapy than in those treated with CCB monotherapy. 6,[15][16][17][18][19][20][21][22] Moreover, a meta-analysis of 82 studies that compared the safety and efficacy of benazepril/amlodipine therapy with that of nine monotherapy regimens concluded that this combination was associated with a lower overall rate of side effects and of side effects that led to withdrawal than either amlodipine or nifedipine monotherapy.…”

“…As CCB-induced oedema is primarily related to vasodilation and not to fluid retention, [10][11][12]23,39 coadministration of a diuretic is not a logical strategy for alleviation of this side effect. 10 In contrast, agents that cause post-capillary dilation (for example, ACEIs and ARBs) are ideally suited for the prevention or reversal of CCB-induced oedema because the normalization of intracapillary pressure induced by these agents will reduce fluid extravasation ( Figure 1).…”

Blood Pressure Effects of High-Dose Amlodipine-Benazepril Combination in Black and White Hypertensive Patients Not Controlled on Monotherapy

“…This hemodynamic imbalance is ameliorated with the addition of ACE inhibitors or ARBs, which cause both arteriolar and venous dilation, enabling the venous system to absorb the excess tissue fluid. [11,12,34,35] In our studies, the incidence of pedal edema tended to be higher with amlodipine monotherapy (9.2%) and improved with the addition of high-dose benazepril (4.5%). Overall, the drugs were well tolerated, and only minor clinical and metabolic side effects occurred, not necessitating patient discontinuation from the studies.…”

Phlebolymphedema–A Common Underdiagnosed and Undertreated Problem in the Wound Care Clinic

“…The actual rate is difficult to determine because it is different for different types of calcium channel blockers and is dose dependent, but rates of 5% to 70% have been reported. 19 Lyrica is a common cause of lower-extremity peripheral edema, and dose dependent rates as high as 17% to 27% have been reported. 20 Brain Natriuretic Peptide (BNP) level is good to rule out congestive heart failure (CHF) because of its high sensitivity of 90%.…”