Clinical features
Peripheral oedema, including ankle oedema, is a recognised side effect of CCBs. It is usually not clinically serious but can reduce treatment adherence and limit use, particularly in older people with multiple comorbidities.
Onset of oedema
CCB-induced oedema usually develops within the first few weeks to months after initiation of therapy or dose increase and commonly affects the ankles and feet. Although it can occur at any time during therapy, it rarely appears in the first few days and is unlikely to be transient or self-limiting.
It is usually bilateral and symmetrical, and tends to worsen in the evening. It may resolve or improve after lying down for several hours. Leg elevation may help but is not essential.
Early symptoms
Early oedema is usually mild, painless, and non-tender, with symptoms such as sensations of tightness or heaviness. There is no associated redness or warmth in the limbs.
Systemic symptoms such as shortness of breath are typically absent.
Effects with prolonged use
With prolonged exposure, oedema may become persistent. Skin changes may occur reflecting increased capillary permeability and erythrocyte leakage, for example:
- petechiae (small red or purple spots caused by minor bleeding under the skin)
- discolouration
- hyperpigmentation
Management
Management of CCB induced oedema depends on severity and individual patient factors.
CCB induced oedema does not resolve on its own and requires active management.
Non-pharmacological options
Elevation of legs when lying down, or graduated compression stockings, may be an option in some individuals with mild oedema.
Optimising the CCB
Where non-pharmacological interventions have failed to achieve adequate control, the next step would be to optimise the CCB.
Reduce the dose
Oedema is dose-related though not always in a dose-proportional manner. Reducing the dosage of the CCB may reduce the severity of oedema.
Switch to another CCB
Switching to another CCB class may reduce oedema, see section on choice of CCB. Options include:
- switching to a non- dihydropyridine (DHP) CCB if suitable, such as verapamil
- switching to a third generation DHP, such a lercanidipine, which has a lower reported incidence of oedema
When switching from one CCB to another, a direct switch can be done. Stop one and start the other at an appropriate dose according to the indication and patient factors. Cross-titration is not required.
Switching to another antihypertensive class
If oedema persists despite optimisation, discontinue the CCB and consider an alternative antihypertensive.
Continuing CCB
In some individuals, discontinuing the CBB may not be clinically appropriate. In these cases, adding in a medicine to counteract the oedema may be considered. This approach should be used cautiously.
Adding a renin-angiotensin system agent
Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to reduce the incidence of CCB-induced oedema.
The mechanism is not fully understood. It may be due to venous dilation reducing capillary hypertension and leakage of fluid into surrounding tissues.
Not recommended
Some drug treatments are not recommended for managing CCB induced oedema.
Diuretics
Thiazide and loop diuretics have little effect on CCB-induced oedema and are not recommended. They reduce fluid overload but do not address vasodilatory fluid pooling.
Nitrates
Although nitrates cause venodilation and may theoretically reduce oedema, their use is not recommended. The need for nitrate-free intervals to prevent tolerance limits their suitability.
Factors affecting incidence
Understanding the factors influencing the incidence of CCB-induced oedema can help reduce this side effect and improve adherence to CCBs.
Person and environmental factors
The risk of developing oedema appears higher in women, older people, and those with heart failure. The risk may also be increased by upright posture, and warm environments.
Dose effects
Oedema is dose related. The incidence of oedema is highest in people taking long-term high doses of DHP agents such as amlodipine, felodipine and nifedipine. However, the degree and severity of oedema is not proportional to the dose.
Duration of action
Short-acting and long-acting CCBs appear to have a similar risk of causing oedema.
Blood pressure effects
The incidence of oedema does not appear to be related to the degree of blood pressure lowering effect of CCBs.
Choice of CCB
Ankle oedema is a class effect in all CCBs. However, the incidence of oedema varies between the DHP and non-DHPs.
Amlodipine and nifedipine
These DHP CCBs are associated with the highest incidence of oedema.
Lercanidipine and lacidipine
These newer lipophilic DHP CCBs are associated with a lower incidence of oedema compared to amlodipine and nifedipine.
Verapamil and diltiazem
These non-DHP CCBs appear less likely to cause oedema. This may be because they have less peripheral vasodilatory effects.
Update history
- Republished
- Full review and update of article. Changes to page structure.
- Published