Should metoprolol or indapamide be added to lisinopril (Angiotensin-Converting Enzyme Inhibitor) for the treatment of Hypertension (HTN)?

From the Guidelines

Adding indapamide to lisinopril is recommended for the treatment of hypertension when lisinopril alone is not sufficient, as indapamide has been shown to be effective in managing resistant hypertension. When considering the addition of another medication to lisinopril, an Angiotensin-Converting Enzyme Inhibitor (ACE inhibitor), for the treatment of hypertension (HTN), it's crucial to evaluate the patient's specific medical history, current blood pressure readings, and other health conditions. According to the 2017 American College of Cardiology/American Heart Association hypertension guideline 1, the treatment of resistant hypertension includes maximization of diuretic therapy, such as using chlorthalidone or indapamide instead of hydrochlorothiazide.

Key Considerations

• The choice between metoprolol, a beta-blocker, and indapamide, a thiazide-like diuretic, depends on factors like the patient's age, heart rate, presence of other conditions such as diabetes or heart failure, and any medication side effects they may experience.
• Indapamide works by removing excess fluid from the body, which can be beneficial for patients with hypertension who may have fluid retention.
• Metoprolol reduces heart rate and cardiac output, which can be beneficial for patients with hypertension who have a high heart rate or cardiac output.

Recommendations

• Indapamide is preferred over metoprolol as an add-on therapy to lisinopril for hypertension treatment, based on the guideline's recommendation for managing resistant hypertension 1.
• A team-based care approach, use of the electronic health record, and patient registries can be beneficial in recognizing uncontrolled hypertension and guiding initiatives for quality improvement in hypertension control 1.
• Telehealth strategies can also be useful adjuncts to interventions shown to lower blood pressure for adults with hypertension 1.

From the FDA Drug Label

In controlled clinical studies of patients with mild to moderate hypertension, patients were treated with lisinopril 20 mg to 80 mg daily, hydrochlorothiazide 12. 5 mg to 50 mg daily or atenolol 50 mg to 200 mg daily; and in other studies of patients with moderate to severe hypertension, patients were treated with lisinopril 20 mg to 80 mg daily or metoprolol 100 mg to 200 mg daily. Lisinopril demonstrated superior reductions of systolic and diastolic compared to hydrochlorothiazide in a population that was 75% Caucasian Lisinopril was approximately equivalent to atenolol and metoprolol in reducing diastolic blood pressure, and had somewhat greater effects on systolic blood pressure. In a small number of controlled studies, indapamide taken with other antihypertensive drugs such as hydralazine, propranolol, guanethidine and methyldopa, appeared to have the additive effect typical of thiazide-type diuretics.

Adding metoprolol or indapamide to lisinopril for the treatment of Hypertension (HTN):

• Metoprolol: may be considered as an add-on therapy to lisinopril, as the drug label shows that lisinopril was approximately equivalent to metoprolol in reducing diastolic blood pressure 2.
• Indapamide: may also be considered as an add-on therapy to lisinopril, as the drug label shows that indapamide had an additive effect when taken with other antihypertensive drugs 3.

From the Research

Treatment of Hypertension with Lisinopril

• Lisinopril is an effective treatment for essential hypertension, with studies showing it to be at least as effective as other common antihypertensive medications such as hydrochlorothiazide, atenolol, metoprolol, and nifedipine 4, 5.
• The addition of hydrochlorothiazide to lisinopril has been shown to enhance its antihypertensive effect, with many patients achieving adequate blood pressure reduction with this combination 4, 5.

Comparison of Lisinopril with Metoprolol

• Studies have compared the efficacy and safety of lisinopril with metoprolol in patients with mild to moderate essential hypertension, with results showing that both medications are effective in reducing blood pressure, but lisinopril is better tolerated and has a more favorable effect on quality of life 6.
• Lisinopril has been shown to produce greater systolic and diastolic blood pressure reductions than metoprolol, with a smoother and more gradual blood pressure reduction 5.

Addition of Indapamide to Lisinopril

• There is evidence to suggest that the addition of indapamide to a renin-angiotensin-aldosterone system (RAAS) inhibitor, such as lisinopril, can improve blood pressure control in patients with uncontrolled hypertension 7.
• A study comparing the antihypertensive effects of indapamide and metoprolol found that the combination of the two medications achieved the best results in reducing blood pressure 8.

Fixed-Dose Combination Therapy

• Fixed-dose combination therapy with a RAAS inhibitor, a diuretic, and a calcium channel blocker has been shown to be effective in improving blood pressure control in patients with uncontrolled hypertension, with a fixed-dose triple combination of perindopril/indapamide/amlodipine being well tolerated and effective in reducing systolic blood pressure and pulse pressure 7.