What is the recommended treatment regimen for patients with hypertension, heart failure, or diabetic nephropathy using Angiotensin-Converting Enzyme (ACE) inhibitors?

From the Guidelines

ACE inhibitors are recommended as first-line therapy for hypertension, heart failure, and diabetic nephropathy, typically starting with a low dose and gradually titrating upward. For hypertension, medications like lisinopril (10-40 mg daily), enalapril (5-40 mg daily in divided doses), or ramipril (2.5-20 mg daily) are commonly prescribed 1. In heart failure, treatment often begins with lower doses such as lisinopril 2.5-5 mg daily or enalapril 2.5 mg twice daily, gradually increasing to target doses of lisinopril 20-40 mg daily or enalapril 10-20 mg twice daily. For diabetic nephropathy, similar medications and dosing strategies apply, with the goal of reducing proteinuria and slowing disease progression.

Key Considerations

• Treatment should be monitored with regular blood pressure checks and laboratory tests for potassium and kidney function within 1-2 weeks of initiation and after dose adjustments 1.
• ACE inhibitors work by blocking the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion, which lowers blood pressure, decreases cardiac workload, and provides renoprotective effects.
• Common side effects include dry cough, hypotension, hyperkalemia, and rarely angioedema, with contraindications in pregnancy, bilateral renal artery stenosis, and history of angioedema.

Monitoring and Adjustments

• Patients treated with an ACE inhibitor, angiotensin receptor blocker, or diuretic, should have serum creatinine/estimated glomerular filtration rate and serum potassium levels monitored at least annually 1.
• Multiple-drug therapy is generally required to achieve blood pressure targets, but combinations of ACE inhibitors and angiotensin receptor blockers should not be used 1.

Special Considerations

• An ACE inhibitor or angiotensin receptor blocker, at the maximally tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and urinary albumin-to-creatinine ratio ≥300 mg/g creatinine or 30–299 mg/g creatinine 1.
• If one class is not tolerated, the other should be substituted 1.

From the FDA Drug Label

In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin converting enzyme inhibitors, including enalapril maleate, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death Lisinopril tablets USP are indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure. Lisinopril tablets USP are indicated to reduce signs and symptoms of systolic heart failure Evaluation of patients with hypertension or heart failure should always include assessment of renal function

The recommended treatment regimen for patients with hypertension, heart failure, or diabetic nephropathy using Angiotensin-Converting Enzyme (ACE) inhibitors is to:

• Use ACE inhibitors, such as enalapril or lisinopril, to lower blood pressure and reduce the risk of cardiovascular events
• Monitor renal function closely, especially in patients with pre-existing renal impairment or those taking diuretics
• Adjust the dosage and/or discontinue the diuretic and/or ACE inhibitor as needed to avoid hyperkalemia and renal failure
• Consider the patient's individual risk factors, such as diabetes and hyperlipidemia, when selecting therapy and determining blood pressure goals 2 3
• Use ACE inhibitors as part of a comprehensive treatment plan that includes lifestyle modifications, such as smoking cessation, exercise, and limited sodium intake. Key considerations:
• Dosage reduction and/or discontinuation of the diuretic and/or ACE inhibitor may be required in patients with renal impairment or hyperkalemia
• Close monitoring of renal function and electrolyte levels is necessary to minimize the risk of adverse events
• Individualized treatment plans should be developed based on the patient's specific needs and risk factors.

From the Research

Recommended Treatment Regimen

The recommended treatment regimen for patients with hypertension, heart failure, or diabetic nephropathy using Angiotensin-Converting Enzyme (ACE) inhibitors is as follows:

• ACE inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions including heart failure and chronic kidney disease 4.
• They are first-line therapy in HTN management along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARB) 4.
• The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has recommended ACE inhibitors, beta blockers, and diuretics as potential first-step agents for the pharmacologic treatment of hypertension 5.

Efficacy and Safety

• ACE inhibitors have been shown to reduce mortality and morbidity in placebo-controlled trials 6.
• However, angiotensin receptor blockers (ARBs) have not shown the same level of efficacy in reducing mortality and morbidity in placebo-controlled trials 6.
• ACE inhibitors are associated with a higher risk of cough and angioedema compared to ARBs 7, 4, 6.
• The number needed to harm for ACE inhibitors is 12 for cough, 20 for hypotension, 23 for dizziness, 31 for hyperkalaemia, and 49 for increased creatinine levels 8.

Comparison with ARBs

• There is no evidence of a difference between ACE inhibitors and ARBs for total mortality, total cardiovascular events, or cardiovascular mortality 6.
• ARBs have a slightly lower incidence of withdrawals due to adverse events (WDAE) compared to ACE inhibitors 6.
• ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment for the management of HTN 4.

Specific Patient Populations

• ACE inhibitors are effective in reducing mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF) 8.
• The number needed to treat to avoid one death at 6 months with ACE inhibitors in HFrEF patients is 50, and at 12 months is 63 8.
• ACE inhibitors can be used to treat congestive heart failure and to prevent the renal complications of hypertension and diabetes mellitus 5.