Switching from Lisinopril to Losartan and Amlodipine for ACE Inhibitor-Induced Cough
Yes, losartan 50 mg and amlodipine 5 mg would be an appropriate and guideline-supported combination to replace lisinopril 20 mg in a patient who developed a dry cough. 1
Rationale for Switching to an ARB
ACE inhibitor-induced cough is a well-documented class effect occurring in 5-35% of patients, caused by accumulation of bradykinin and substance P, and switching to an ARB is the Grade A recommendation when this occurs. 1
Losartan specifically has been proven in controlled trials to have a dramatically lower incidence of cough (17-29%) compared to lisinopril (62-69%) in patients with prior ACE inhibitor-induced cough, with cough rates similar to placebo or hydrochlorothiazide. 2, 3
The FDA label explicitly states that in two prospective, double-blind, randomized controlled trials, losartan 50 mg had cough incidence of 17% and 29% versus lisinopril 20 mg at 69% and 62%, demonstrating that losartan's cough incidence is similar to placebo in patients who previously had ACE inhibitor-induced cough. 2
Recommended Combination Therapy Strategy
The combination of an ARB (losartan) plus a calcium channel blocker (amlodipine) is explicitly listed as one of the preferred and well-established combinations for hypertension by the European Society of Cardiology. 4
This combination has complementary mechanisms of action: losartan blocks the renin-angiotensin system while amlodipine provides vasodilation through calcium channel blockade, resulting in additive blood pressure-lowering effects. 4
The combination of ARB + calcium channel blocker is proven to be effective and well-tolerated, with evidence from multiple controlled trials showing superior blood pressure control compared to monotherapy. 4, 5
Specific Dosing Recommendations
Start with losartan 50 mg once daily, which is the appropriate initial dose for hypertension and matches the dose used in the clinical trials demonstrating low cough incidence. 1, 2
Amlodipine 5 mg once daily is an appropriate starting dose and can be combined with losartan from the outset, as fixed-dose combinations simplify treatment and optimize compliance. 4
If blood pressure control is inadequate after 2-4 weeks, losartan can be titrated to 100 mg once daily (the maximum recommended dose for hypertension), though higher doses up to 150 mg daily may be considered in heart failure patients. 6
Critical Monitoring Parameters
Monitor blood pressure, serum creatinine/eGFR, and potassium levels within 1-2 weeks after initiating losartan therapy, as ARBs can cause hyperkalemia and affect renal function similar to ACE inhibitors. 1, 6
The cough should resolve within 1-4 weeks after discontinuing lisinopril and switching to losartan, though it may take up to 3 months in some patients. 1
Monitor for postural blood pressure changes, particularly in elderly patients, as the combination of ARB and calcium channel blocker can cause orthostatic hypotension. 1
Important Safety Considerations and Pitfalls to Avoid
Never combine losartan with an ACE inhibitor (dual RAS blockade), as this increases the risk of hyperkalemia, syncope, and acute kidney injury without providing additional cardiovascular benefit. 7, 6
Although rare, angioedema has been reported with ARBs in patients who previously experienced angioedema with ACE inhibitors; monitor closely during initial treatment. 1, 2
Be aware that while uncommon, cases of cough have been reported with losartan in postmarketing experience, though the incidence remains dramatically lower than with ACE inhibitors. 2, 8
Alternative Considerations if Losartan is Not Tolerated
If losartan causes cough (rare but possible), other ARBs such as candesartan 4-8 mg once daily or valsartan 40-80 mg once daily can be considered, as all ARBs have equivalent low cough profiles. 1
If blood pressure remains uncontrolled on losartan 100 mg plus amlodipine 10 mg, adding a thiazide diuretic (hydrochlorothiazide 12.5-25 mg daily or indapamide 2.5 mg daily) is the preferred third agent. 7