From the Guidelines
Not all calcium channel blockers (CCBs) pose the same risk of peripheral edema, with dihydropyridine CCBs having a higher risk compared to non-dihydropyridine CCBs. 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 provides evidence on the different classes of CCBs and their associated risks.
Key Points
- Dihydropyridine CCBs, such as amlodipine, felodipine, and nifedipine, are associated with a dose-related pedal edema, which is more common in women than men 1.
- Non-dihydropyridine CCBs, such as diltiazem and verapamil, cause significantly less edema, with rates typically below 5% 1.
- The difference in edema risk between dihydropyridine and non-dihydropyridine CCBs occurs because dihydropyridines primarily affect peripheral blood vessels, causing arterial dilation without corresponding venous dilation, which leads to increased hydrostatic pressure and fluid leakage into tissues.
Management of Edema
- If a patient develops troublesome edema on a dihydropyridine CCB, switching to a non-dihydropyridine alternative like diltiazem may help reduce this side effect while still providing blood pressure control 1.
- Dose reduction can also help minimize edema, as can combining a CCB with an ACE inhibitor or ARB, which can counteract the edema-producing effects through balanced arterial and venous dilation 1.
From the FDA Drug Label
Edema 1.8 3.0 10.8 0.6 ... Edema 5.6 14.6 1.4 5.1 ... Peripheral edema is experienced by some patients.
The risk of peripheral edema is not the same for all calcium channel blockers, as the provided information only discusses amlodipine. Peripheral edema is a known side effect of amlodipine, with a dose-dependent incidence, but the FDA label does not provide a direct comparison to other calcium channel blockers. 2
From the Research
Risk of Peripheral Edema with Calcium Channel Blockers
- The risk of peripheral edema is not the same for all calcium channel blockers (CCBs) 3, 4, 5, 6, 7
- Dihydropyridine CCBs have a higher incidence of peripheral edema compared to non-dihydropyridine CCBs 4, 5
- Lipophilic dihydropyridine CCBs, such as lercanidipine and lacidipine, may have a lower risk of peripheral edema compared to traditional dihydropyridine CCBs 4, 5, 6, 7
- The risk of peripheral edema also varies among individual CCBs, with nifedipine having a higher risk and lacidipine having a lower risk 5, 6
Factors Influencing the Risk of Peripheral Edema
- The dose of the CCB can influence the risk of peripheral edema, with higher doses associated with a higher risk 4, 6
- The duration of therapy with CCBs can also influence the risk of peripheral edema, with the risk increasing over time 4
- Combination therapy with renin-angiotensin system blockers or diuretics may reduce the risk of peripheral edema associated with CCBs 3, 5
Comparison of Individual CCBs
- Nifedipine has a higher risk of peripheral edema compared to lacidipine 5, 6
- Amlodipine has a higher risk of peripheral edema compared to lacidipine 6
- Lercanidipine has a lower risk of peripheral edema compared to first-generation dihydropyridine CCBs, but not compared to second-generation dihydropyridine CCBs 7