Which medication, Amlodipine or Losartan, is more likely to cause peripheral edema (swelling)?

Amlodipine Causes Swelling

Amlodipine is significantly more likely to cause peripheral edema (swelling) than losartan, with edema occurring in approximately 16.6% of patients on amlodipine compared to minimal risk with losartan. 1, 2

Mechanism of Amlodipine-Induced Edema

• Amlodipine causes peripheral edema through preferential dilation of pre-capillary arterioles, which increases capillary hydrostatic pressure without causing true fluid retention or volume overload 3
• This mechanism is fundamentally different from volume-related edema, which is why diuretics show inconsistent benefit 3
• The edema is dose-dependent, occurring in 1.8% at 2.5 mg, 3.0% at 5 mg, and 10.8% at 10 mg doses 1

Clinical Evidence Comparing Edema Risk

• Meta-analysis data demonstrates that amlodipine increases edema risk nearly 3-fold compared to placebo (16.6% vs 6.2%, risk ratio 2.9), with the placebo-adjusted rate showing that 63% of edema cases are truly drug-related 2
• Women experience significantly higher rates of amlodipine-induced edema than men (14.6% vs 5.6%), representing a 2.6-fold increased risk 1, 3
• Higher doses (10 mg) produce substantially more edema (risk ratio 3.08) compared to lower doses of 2.5-5 mg (risk ratio 2.01) 2

Losartan and Edema

• Losartan, as an angiotensin receptor blocker (ARB), does not cause peripheral edema through its mechanism of action 3, 4
• In fact, combining losartan or other ARBs with amlodipine significantly reduces amlodipine-induced edema incidence (6.6% with combination vs 31.1% with amlodipine 10 mg alone) 5
• Adding telmisartan (another ARB) to amlodipine reduced ankle foot volume increase from 26.7% to 7.9% 6

Management Algorithm When Edema Occurs

• The American College of Cardiology recommends switching to an alternative antihypertensive agent (such as ACE inhibitors, ARBs like losartan, or thiazide diuretics) as first-line management rather than adding diuretics 3, 4
• Combining amlodipine with an ARB (like losartan) may reduce edema incidence while maintaining blood pressure control 4, 5
• Loop diuretics have variable effectiveness for calcium channel blocker-induced edema and are not the preferred initial strategy 3

Critical Pitfalls

• Avoid empirically adding diuretics as first-line treatment, since amlodipine-induced edema is not due to volume overload 3
• Avoid amlodipine entirely in patients with pulmonary edema or severe left ventricular dysfunction 3, 4
• Do not assume all edema in patients on amlodipine is drug-related—evaluate for venous insufficiency, heart failure, or renal disease 4
• Avoid abrupt discontinuation without implementing alternative blood pressure management to prevent rebound hypertension 4