From the Guidelines
For heart failure, a good starting dose of an ACE inhibitor is typically low, such as lisinopril at 2.5-5 mg once daily, enalapril at 2.5 mg twice daily, or ramipril at 1.25-2.5 mg once daily, and then gradually increased as tolerated. These lower initial doses are particularly important for patients who may be at risk for hypotension, including those on diuretics, the elderly, or those with renal impairment.
Key Considerations
- The dose should be doubled approximately every 2 weeks as tolerated until reaching the target dose (lisinopril 20-40 mg daily, enalapril 10-20 mg twice daily, or ramipril 10 mg daily) or the maximum tolerated dose 1.
- Blood pressure, renal function, and potassium levels should be monitored within 1-2 weeks after initiation and after each dose increase 1.
- ACE inhibitors work by blocking the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and sodium retention, which decreases cardiac workload and improves symptoms and survival in heart failure patients.
Monitoring and Adjustments
- Renal function and serum potassium should be assessed within 1 to 2 weeks of initiation of therapy and periodically thereafter, especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, azotemia, or in those taking potassium supplements 1.
- A specialist HF nurse may assist with education of the patient, follow-up, biochemical monitoring, and dose up-titration 1.
Evidence-Based Recommendations
- The available data suggest that there are no differences among ACE inhibitors in their effects on symptoms or survival 1.
- Treatment with an ACE inhibitor should be initiated at low doses, followed by gradual dose increments if lower doses have been well tolerated 1.
From the FDA Drug Label
In the placebo-controlled studies that demonstrated improved survival, patients were titrated as tolerated up to 40 mg, administered in two divided doses. The recommended initial dose is 2.5 mg. The recommended dosing range is 2. 5 to 20 mg given twice a day. Doses should be titrated upward, as tolerated, over a period of a few days or weeks.
- Initial dose: 2.5 mg
- Dosing range: 2.5 to 20 mg given twice a day
- Titration: upward, as tolerated, over a few days or weeks 2
From the Research
Starting Dose for ACE Inhibitors in Heart Failure
- The optimal starting dose for ACE inhibitors in heart failure is not explicitly stated in the provided studies, but it is recommended to start with a low dose and titrate up to the target dose used in clinical trials, if tolerated 3.
- A study comparing enalapril and perindopril found that a low dose of 2.5 mg enalapril or 2.0 mg perindopril was used as the starting dose, with perindopril causing less first-dose hypotension 4.
- Another study used perindopril as the starting ACE inhibitor, with a target dose of at least 4 mg/day, and found that specialist heart failure nurse supervised rapid titration to target dose was safe and feasible in a community heart failure population 5.
Target Dose for ACE Inhibitors in Heart Failure
- The target dose for ACE inhibitors in heart failure is the dose used in clinical trials, which has been shown to reduce morbidity and mortality 3, 6.
- Examples of target doses for specific ACE inhibitors include:
- A systematic review and meta-analysis found that high-dose ACE inhibitors did not significantly reduce all-cause or cardiovascular mortality compared to low-dose ACE inhibitors, but did increase functional capacity and the risk of hypotension 7.