What is the starting dose of an Angiotensin-Converting Enzyme (ACE) inhibitor?

From the Guidelines

The starting dose of an ACE inhibitor should be initiated at a low dose, with gradual dose increments if the lower doses are well tolerated, as recommended by the 2013 ACCF/AHA guideline for the management of heart failure 1. When initiating ACE inhibitors, it's essential to consider the specific medication and the patient's clinical condition.

• For most patients with hypertension or heart failure, the starting dose can be as follows:
  • Lisinopril: 2.5-5 mg daily for heart failure patients, or 10 mg once daily for hypertension patients
  • Enalapril: 2.5 mg twice daily for heart failure patients, or 5 mg twice daily for hypertension patients
  • Ramipril: 1.25-2.5 mg daily for heart failure patients, or 2.5 mg once daily for hypertension patients
• Patients with renal impairment, volume depletion, or those on diuretics should start at lower doses to prevent first-dose hypotension, as suggested in the 2005 ACC/AHA guideline update for the diagnosis and management of chronic heart failure in the adult 1.
• Elderly patients typically require lower initial doses as well. The doses can then be titrated upward every 2-4 weeks as tolerated to reach target blood pressure or the maximum recommended dose, while monitoring blood pressure, renal function, and potassium levels within 1-2 weeks of starting therapy, as recommended by the 2013 ACCF/AHA guideline 1. ACE inhibitors work by blocking the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion, which leads to vasodilation and decreased blood pressure, as explained in the 2005 ACC/AHA guideline update 1. This mechanism explains why patients with volume depletion are more susceptible to significant blood pressure drops when starting these medications. It is crucial to follow the guidelines and adjust the doses according to the patient's response and tolerance, to minimize the risk of adverse reactions and maximize the benefits of ACE inhibitors, as suggested by the 2013 ACCF/AHA guideline 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION 2. 1 Hypertension Initial Therapy in adults: The recommended initial dose is 10 mg once a day. The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day. 2. 2 Heart Failure The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. 2. 3 Reduction of Mortality in Acute Myocardial Infarction In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril tablets 5 mg orally 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 starting dose of an ACE inhibitor, specifically lisinopril, varies based on the condition being treated:

• Hypertension: 10 mg once a day for adults not taking diuretics, and 5 mg once a day for adults taking diuretics.
• Heart Failure: 5 mg once daily, with a reduced dose of 2.5 mg once daily for patients with hyponatremia.
• Acute Myocardial Infarction: 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours, and then 10 mg once daily.
• Renal Impairment: No dose adjustment is needed for creatinine clearance > 30 mL/min, but for patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, the initial dose should be reduced to half of the usual recommended dose 2.

From the Research

Starting Dose of an ACE Inhibitor

• The starting dose of an ACE inhibitor should be carefully considered to avoid first-dose hypotension, which can occur in patients with heart failure, severe hypertension, or renovascular hypertension 3.
• In patients with chronic heart failure, the initial dose of an ACE inhibitor should be low, such as 2.5 mg of enalapril or 2.0 mg of perindopril, to minimize the risk of first-dose hypotension 4.
• In pediatric patients with heart failure, the starting dose of an ACE inhibitor, such as captopril or enalapril, should be small and gradually increased to the target dose to prevent excessive hypotension 5.
• Patients with renal insufficiency may require a lower starting dose of an ACE inhibitor, as they are at higher risk of developing hyperkalemia and worsening renal function 6.
• The dose of an ACE inhibitor should be titrated based on the patient's response, with regular monitoring of blood pressure, renal function, and electrolytes to minimize the risk of adverse effects 6, 3, 5, 7.

Factors Influencing Starting Dose

• Renal function: Patients with renal insufficiency may require a lower starting dose of an ACE inhibitor 6.
• Heart failure: Patients with heart failure may be at higher risk of first-dose hypotension and may require a lower starting dose of an ACE inhibitor 3, 4.
• Age: Elderly patients may be at higher risk of first-dose hypotension and may require a lower starting dose of an ACE inhibitor 3.
• Concomitant medications: Patients taking diuretics or other medications that may interact with ACE inhibitors may require a lower starting dose of an ACE inhibitor 6, 7.

Monitoring and Titration

• Regular monitoring of blood pressure, renal function, and electrolytes is necessary to minimize the risk of adverse effects and to titrate the dose of the ACE inhibitor 6, 3, 5, 7.
• Patients should be closely observed for at least 6 hours after the initial dose of an ACE inhibitor to monitor for first-dose hypotension 3.
• The dose of the ACE inhibitor should be titrated based on the patient's response, with gradual increases in dose to minimize the risk of adverse effects 6, 3, 5, 7.