What is the recommended alternative for a patient experiencing angioedema and bilateral lower extremity edema while taking losartan (Losartan potassium) 100 mg daily for hypertension?

From the Guidelines

I strongly recommend discontinuing losartan potassium immediately and replacing it with a non-ARB, non-ACE inhibitor antihypertensive medication, such as a calcium channel blocker like amlodipine 5-10 mg daily or a thiazide diuretic like chlorthalidone 12.5-25 mg daily, as suggested by 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. The patient is experiencing angioedema and significant bilateral lower extremity edema, which are known adverse effects of angiotensin receptor blockers (ARBs) like losartan.

• A suitable alternative would be a calcium channel blocker such as amlodipine 5-10 mg daily, which is associated with dose-related pedal edema, but this is more common in women than men, as noted in the guideline 1.
• The diuretic, such as chlorthalidone, would be particularly beneficial in addressing the edema while also controlling blood pressure, and is preferred on the basis of prolonged half-life and proven trial reduction of CVD, as stated in the guideline 1. This recommendation is based on the mechanism of ARBs, which can cause bradykinin accumulation leading to angioedema, a potentially life-threatening condition.
• Additionally, the patient should be monitored closely after discontinuation as angioedema may take several days to resolve completely.
• The patient should be instructed to seek immediate medical attention if they experience any difficulty breathing, throat tightness, or facial swelling, as these could indicate progression of the angioedema to a more serious condition. It is also important to note that the guideline recommends avoiding the use of ACE inhibitors in patients with a history of angioedema with ACE inhibitors, and ARBs in patients with a history of angioedema with ARBs, but patients with a history of angioedema with an ACE inhibitor can receive an ARB beginning 6 weeks after ACE inhibitor is discontinued 1.

From the Research

Alternative Therapies for Hypertension

Given the patient's experience with angioedema and bilateral lower extremity edema while taking losartan, alternative therapies should be considered.

• Amlodipine, a calcium channel blocker, has been shown to be effective in treating essential hypertension 2.
• The study found that amlodipine is more effective than losartan potassium in respect to treatment of essential hypertension, with a reduction of systolic blood pressure (SBP) of 5.19±2.93mm of Hg versus 3.27±1.34mm of Hg (p<0.001) and reduction of diastolic blood pressure (DBP) of 1.7±0.70 mm of Hg versus 0.68 mm of Hg (p<0.001) 2.
• Amlodipine may be a suitable alternative for patients who experience adverse effects with losartan, such as angioedema 2.

Considerations for Losartan Use

While losartan is generally well-tolerated, it can cause adverse effects such as angioedema, hyperkalemia, headache, and dizziness 3, 2, 4.

• Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect, also occurs with losartan potassium 3.
• The risk of angioedema may be increased when losartan is combined with other medications, such as atorvastatin 5.

Dose Adjustment and Combination Therapy

• Losartan can be combined with hydrochlorothiazide to reduce blood pressure further than either drug given separately 3, 4.
• The dose of losartan can be titrated to 100 mg in cases of poor blood pressure response 6.