From the Guidelines
Antihypertensive medications, particularly calcium channel blockers (CCBs) like amlodipine, felodipine, and nifedipine, are the primary cause of pedal edema due to their vasodilatory effects, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
Mechanism of Pedal Edema
The mechanism behind this side effect involves the dilation of arterioles more than venules, creating a pressure gradient that forces fluid from the vascular space into surrounding tissues, especially in the lower extremities where gravity enhances this effect. This fluid accumulation manifests as swelling in the feet and ankles.
Prevalence and Risk Factors
Dihydropyridine CCBs are most frequently associated with this side effect, with up to 30% of patients taking amlodipine experiencing pedal edema. The edema is typically dose-dependent and more common in women and older adults, as noted in the guideline 1.
Management Options
Management options include:
- Reducing the dose of the CCB
- Switching to a different class of antihypertensive
- Adding an ACE inhibitor or ARB, which can counteract the edema by dilating both arterioles and venules
- Using diuretics to reduce fluid retention
Clinical Considerations
The edema is generally benign but can affect medication adherence due to discomfort and cosmetic concerns. Therefore, it is essential to weigh the benefits of using CCBs against the potential for pedal edema and to consider alternative treatment options when necessary, as recommended in the guideline 1.
From the Research
Antihypertensives and Pedal Oedema
- Antihypertensives, particularly calcium channel blockers (CCBs), can cause pedal oedema as a side effect 2, 3, 4.
- The incidence of leg oedema can be markedly reduced by combining CCBs with a blocker of the renin-angiotensin system 2.
- Third-generation CCBs, such as lercanidipine, have been shown to have a comparable antihypertensive efficacy to older CCBs like amlodipine, but with significantly less peripheral oedema 2, 3.
- High doses of dihydropyridine CCBs often cause oedema, headache, flushing, and tachycardia 4.
- The exact mechanism of CCB-induced oedema is not fully understood, but it is thought to be related to the vasodilatory effects of these drugs on the blood vessels, leading to increased fluid leakage into the interstitial tissue.
Management of Pedal Oedema
- Combining CCBs with other antihypertensive agents, such as blockers of the renin-angiotensin system, can help reduce the incidence of oedema 2, 5.
- Using third-generation CCBs, such as lercanidipine, may be an alternative to reduce the risk of oedema 2, 3.
- Monitoring patients for signs of oedema and adjusting the treatment regimen as needed is essential to minimize the risk of this side effect.