If a patient experiences a cough with 5mg of lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor), is 25mg of losartan (Angiotensin II Receptor Blocker (ARB)) the best equivalent?

From the Guidelines

Yes, 25mg of losartan is an appropriate equivalent for a patient who experienced a cough with 5mg of lisinopril. ACE inhibitor-induced cough is a common side effect occurring in 5-35% of patients taking medications like lisinopril, as noted in the guidelines 1. This cough results from the accumulation of bradykinin and substance P in the lungs, which ACE inhibitors prevent from breaking down. Switching to an ARB like losartan is recommended because ARBs work differently by blocking angiotensin II receptors rather than inhibiting ACE, thus avoiding bradykinin accumulation while still providing similar cardiovascular benefits. The standard starting dose of losartan is 25-50mg once daily, making 25mg an appropriate starting point, as indicated in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. When switching, discontinue lisinopril and wait 24-48 hours before starting losartan to minimize overlap. Monitor blood pressure after switching to ensure adequate control, as individual responses may vary. Losartan can be taken with or without food, typically once daily. If blood pressure control is inadequate, the dose can be increased to 50-100mg daily as needed, according to the guidelines 1. Key points to consider when making this switch include:

• The mechanism of action of ARBs and how they differ from ACE inhibitors
• The dosage and administration of losartan
• The importance of monitoring blood pressure after the switch
• The potential for adjusting the dose of losartan based on patient response. Overall, switching to losartan is a reasonable approach for managing ACE inhibitor-induced cough, as supported by the evidence 1.

From the FDA Drug Label

The incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown in Table 1 below Table 1 Study 1 HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 Placebo Losartan Lisinopril Cough 35% 29% 62%

The best equivalent dose of losartan for a patient who experiences a cough with 5mg of lisinopril is not directly stated in the label.

• However, the label does mention that losartan 50mg was used in clinical trials to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy.
• The label also mentions that the incidence of cough associated with losartan therapy is similar to that associated with hydrochlorothiazide or placebo therapy.
• Since 25mg of losartan is half of the dose used in the clinical trials, it may not be the best equivalent dose for this patient.
• The patient's response to losartan may vary, and the incidence of cough may be different from that reported in the clinical trials 2.

From the Research

Equivalent Dosage

• The patient is experiencing a cough with 5mg of lisinopril, an Angiotensin-Converting Enzyme (ACE) inhibitor.
• Losartan, an Angiotensin II Receptor Blocker (ARB), is being considered as an alternative.

Cough Incidence with Losartan and Lisinopril

• Studies have shown that the incidence of cough is lower with losartan compared to lisinopril 3, 4, 5.
• In one study, the incidence of cough with losartan 50mg was 29%, compared to 72% with lisinopril 20mg 3.
• Another study found that the incidence of dry cough was significantly higher in the lisinopril group (87.5%) compared to the losartan group (36.7%) 4.

Dosage Comparison

• The dosage of losartan being considered is 25mg, which is half of the dosage used in some of the studies (50mg) 3, 4, 5.
• However, there is no direct evidence to suggest that 25mg of losartan is the best equivalent to 5mg of lisinopril.

Alternative Options

• Other studies have compared the incidence of cough with different ARBs, such as telmisartan, and found that they have a lower incidence of cough compared to lisinopril 6.
• These findings suggest that ARBs may be a suitable alternative for patients who experience a cough with ACE inhibitors.