What is the management approach for a patient with hypertension who is already on lisinopril (Angiotensin-Converting Enzyme Inhibitor), amlodipine (Calcium Channel Blocker), and thiazide (Diuretic)?

From the Guidelines

For a patient with hypertension who remains uncontrolled despite being on lisinopril, amlodipine, and a thiazide diuretic, I recommend adding spironolactone 25mg daily as a fourth agent, provided their serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2, as suggested by the 2020 international society of hypertension global hypertension practice guidelines 1. Before adding another medication, it is crucial to exclude causes of pseudoresistance, including poor BP measurement technique, white coat effect, nonadherence, and suboptimal choices in antihypertensive therapy, as outlined in the guidelines 1.

Key Considerations

• Ensure the patient is taking their current medications consistently and that their blood pressure readings are accurate using proper technique and validated devices.
• Optimize the current treatment regimen, including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics and optimal choice of diuretic.
• Consider screening patients for secondary causes of hypertension as appropriate.
• If spironolactone is contraindicated or not tolerated, alternative fourth-line options include amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, or any available antihypertensive class not already in use, as suggested by the guidelines 1.

Monitoring and Follow-Up

• Monitor potassium and renal function after adding spironolactone, especially in patients also taking an ACE inhibitor like lisinopril.
• Resistant hypertension should be managed in specialist centers with sufficient expertise and resources necessary to diagnose and treat this condition, according to the guidelines 1.

From the FDA Drug Label

DRUG INTERACTIONS 7. 1 Diuretics Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril. If this is not possible, reduce the starting dose of lisinopril [see Dosage and Administration (2. 2)and Warnings and Precautions (5.4)]. Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently.

The management approach for a patient with hypertension who is already on lisinopril (Angiotensin-Converting Enzyme Inhibitor), amlodipine (Calcium Channel Blocker), and thiazide (Diuretic) includes:

• Monitoring the patient's serum potassium frequently due to the risk of hyperkalemia with concomitant use of potassium-sparing diuretics
• Being aware of the potential for excessive reduction of blood pressure when initiating lisinopril in patients on diuretics
• Considering reducing the starting dose of lisinopril if the patient is already on a diuretic and it is not possible to decrease or discontinue the diuretic or increase salt intake prior to initiation of treatment with lisinopril 2
• Monitoring renal function and electrolytes in patients on lisinopril and other agents that affect the renin-angiotensin system, such as amlodipine is not necessary as per the label, but blood pressure should be monitored 2

From the Research

Management Approach for Hypertension

The management approach for a patient with hypertension who is already on lisinopril (Angiotensin-Converting Enzyme Inhibitor), amlodipine (Calcium Channel Blocker), and thiazide (Diuretic) involves considering the addition of other antihypertensive agents or adjusting the current medication regimen.

• The combination of lisinopril and amlodipine has a synergistic effect in patients with more severe hypertension 3.
• Adding a thiazide diuretic to the combination of amlodipine and lisinopril can cause a significant fall in blood pressure compared to adding a beta-blocker or placebo 3.
• The combination of amlodipine plus valsartan and lisinopril plus hydrochlorothiazide are well-tolerated and efficacious in achieving blood pressure reduction in patients with stage 2 hypertension 4.
• The combination of lisinopril and amlodipine is optimal and universal for effective treatment of patients with hypertension in combination with arteriosclerosis obliterans in all types of central hemodynamics 5.
• Consideration of adding other antihypertensive agents such as doxazosin to amlodipine can provide an additional fall in blood pressure, suggesting its potential as an effective add-on treatment to calcium-channel blockers 6.

Considerations for Combination Therapy

When considering combination therapy for hypertension, the following points should be taken into account:

• ACEIs and ARBs should not be used simultaneously 7.
• In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker 7.
• Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB, followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status 7.
• Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker 7.
• Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB 7.