What is the appropriate second antihypertensive agent for a patient with impaired renal function who is already taking maximum doses of Amlodipine (calcium channel blocker)?

From the Guidelines

For a patient with kidney injury who is already on maximum-dose amlodipine and needs a second antihypertensive, I recommend adding a beta blocker, such as metoprolol succinate 50-200 mg daily, as the preferred second agent, 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. Start at a low dose and titrate slowly while monitoring renal function and potassium levels closely, checking labs within 1-2 weeks of initiation. Some key points to consider when choosing a second antihypertensive agent include:

• The patient's kidney function, as some agents may be more suitable for patients with mild versus severe kidney injury
• The presence of proteinuria, which may influence the choice of agent
• The risk of hyperkalemia, which may be increased with certain agents, such as ACE inhibitors or ARBs, especially in patients with severe kidney injury or those taking potassium-sparing diuretics
• The need to balance effective blood pressure control with the need to protect remaining kidney function. Some alternative options to consider include:
• A diuretic, such as furosemide 20-80 mg daily, for patients with volume overload
• An alpha-1 blocker, such as doxazosin 1-16 mg daily, for patients with concomitant benign prostatic hyperplasia (BPH)
• A central alpha2-agonist, such as clonidine 0.1-0.8 mg daily, for patients who are unable to tolerate other agents. However, these alternatives should be chosen based on individual patient characteristics and clinical judgment, taking into account the potential benefits and risks of each agent, as outlined in the guidelines 1.

From the FDA Drug Label

Use with diuretics in adults If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12. 5 mg). 2. 4 Dose in Patients with Renal Impairment No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2. 5 mg. The patient with kidney injury who is maxed out on amlodipine may be considered for lisinopril as a second antihypertensive.

• The recommended starting dose for patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min is half of the usual recommended dose, which is 2.5 mg for hypertension.
• Dose titration should be done cautiously and as tolerated to a maximum of 40 mg daily. 2

From the Research

Patient with Kidney Injury Maxed Out on Amlodipine

Second Antihypertensive Options

• When a patient with kidney injury is maxed out on amlodipine, consideration of a second antihypertensive is necessary 3.
• Studies have shown that angiotensin-converting enzyme (ACE) inhibitors, such as enalapril, can have protective effects on renal function, similar to amlodipine 3.
• However, ACE inhibitors can also cause reversible impairment of renal function, as seen in a case report of a 72-year-old patient treated with lisinopril 4.
• The use of combined therapy with an ACE inhibitor and an angiotensin II receptor blocker (ARB) has been gaining support, but limited data is available regarding this treatment in patients with kidney injury 5.

Considerations for Second Antihypertensive

• Amlodipine has been shown to have protective effects on renal function, and its use before contrast exposure may play a role in protecting hypertensive patients from contrast-induced acute kidney injury (CI-AKI) and prolonging survival 6.
• ACE inhibitors, such as lisinopril, may be associated with a lower risk of mortality and renal replacement therapy-free days, but their use in patients with acute kidney injury (AKI) remains unclear 7.
• The choice of a second antihypertensive should be based on individual patient characteristics, including the severity of kidney injury and the presence of other comorbidities.
• Close surveillance of renal function and blood pressure is necessary when initiating a second antihypertensive, especially in patients with kidney injury 5.