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

Domenic A. Sica, MD

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In This Article

Frequency of Edema With CCB Therapy

The frequency with which CCB treatment is accompanied by peripheral edema is both compound-specific and dose-dependent. Therefore, a more potent CCB like amlodipine will be associated with higher rates of edema development than a somewhat lower-potency CCB like diltiazem.[10] Reported frequency rates for peripheral edema with CCB therapy are quite varied in the literature in part because of the dose-dependent nature of the phenomenon, and can range from 5% to as high as 70%.[11,12,13,14,15]

Several considerations should be accounted for when attempting to determine the purported frequency of CCB-related edema. First, the reporting system for peripheral edema varies from study to study. The reported frequency of edema is clearly influenced by the method of diagnosis. Edema frequency can be determined from patient self-report,[13] but self-report can overestimate edema frequency because a simple sense of fullness in the lower extremities often is registered as a positive patient response. Edema frequency can also be determined by simple yes/no responses to standardized questions. If this process is repeated several times during a clinical trial, the repetitive nature of the process can result in a learned response pattern. This may be the basis for positive edema reports with either placebo or active therapy that otherwise would not be associated with edema.[12] Finally, edema rates can be ascertained by physical examination combined with careful questioning with slotting into categories of mild, moderate, or severe edema by prospectively established criteria.[12]

A study by Kloner et al.[12] illustrates the difficulty of accurately reporting edema frequency and severity: "The degree of peripheral edema was assessed at each visit by applying gentle pressure to elicit 'pitting' and was ranked as mild, moderate, or severe according to the following criteria. Mild: edema was present on examination, but the patient was not aware of it (asymptomatic); the edema did not interfere with daily living, and the patient was willing to continue study medication. Moderate: edema was present on examination, and the patient was aware of it (symptomatic); the edema did or did not interfere with daily living, and the patient was willing to continue study medication. Severe: edema was present on examination, and the patient was aware of it (symptomatic); the edema interfered with daily living, and the patient was unwilling to continue study medication." Although objective criteria were used for determining the presence of edema in that study, the category assignment was extremely subjective.

Each of these modes of frequency ascertainment also falls short in that the background frequency of peripheral edema before the start of CCB therapy is rarely identified. Transient peripheral edema is quite common in the general population relating to posture, climactic conditions, and age.[7]

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