What is the recommended treatment and dosage for patients with hypertension and heart failure using Angiotensin-Converting Enzyme (ACE) inhibitors?

ACE Inhibitors for Hypertension and Heart Failure

ACE inhibitors are first-line therapy for both hypertension and heart failure with reduced ejection fraction, and you must titrate to target doses proven in clinical trials—not just to symptom relief or blood pressure control—because achieving these target doses significantly reduces mortality and hospitalizations. 1, 2

Starting ACE Inhibitors

Initial Dosing by Indication

For hypertension:

• Start lisinopril 10 mg once daily in patients not on diuretics 3
• Start lisinopril 5 mg once daily if patient is already taking a diuretic 3
• Start enalapril 5 mg once daily in patients not on diuretics 4
• Start enalapril 2.5 mg once daily if patient is already taking a diuretic 4

For heart failure:

• Start lisinopril 2.5-5 mg once daily 2, 3
• Start enalapril 2.5 mg once daily 2, 4
• Use 2.5 mg starting dose if serum sodium <130 mEq/L 3

Target Doses: The Critical Component

You must aim for these specific target doses because they are what reduced mortality in clinical trials—lower doses may control symptoms or blood pressure but do not provide the same survival benefit: 1, 2

ACE Inhibitor	Starting Dose	Target Dose
Lisinopril	2.5-5 mg once daily	30-35 mg once daily [2]
Enalapril	2.5 mg twice daily	10-20 mg twice daily [2]
Ramipril	2.5 mg once daily	5 mg twice daily or 10 mg once daily [2]
Captopril	6.25 mg three times daily	50-100 mg three times daily [2]

For hypertension specifically, lisinopril target is 20-40 mg once daily (up to 80 mg has been used but provides no additional benefit). 3

Titration Protocol

Double the dose every 2 weeks minimum until you reach target dose or maximum tolerated dose. 1, 2 This is non-negotiable—the evidence shows that higher doses provide better outcomes. 1, 5

Monitoring Schedule

• Check blood pressure, renal function (creatinine), and potassium 1-2 weeks after each dose increase 1, 2
• Recheck at 3 months after reaching target dose 1, 2
• Then monitor every 6 months 1, 2

Acceptable Laboratory Changes During Titration

Do not stop or reduce the ACE inhibitor for these laboratory changes—they are expected and acceptable: 2

• Creatinine increase up to 50% above baseline OR up to 3 mg/dL (whichever is greater) is acceptable 2
• Potassium up to 5.5-6.0 mmol/L is acceptable 2

These changes reflect the drug's mechanism of action and do not require dose reduction unless they exceed these thresholds.

When to Seek Specialist Input

Refer to a specialist before initiating ACE inhibitors in these situations: 1

• Bilateral renal artery stenosis 1
• Baseline creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 1
• Baseline potassium >5.0 mEq/L 1
• History of angioedema with previous ACE inhibitor use 1

Combination Therapy Approach

For Hypertension with Heart Failure

Follow this stepwise algorithm: 1

1. Step 1: Start with ACE inhibitor (or ARB), beta-blocker, and mineralocorticoid receptor antagonist (MRA) as first-, second-, and third-line therapy 1
2. Step 2: Add thiazide diuretic (or switch to loop diuretic if already on thiazide) if blood pressure remains uncontrolled 1
3. Step 3: Add amlodipine or hydralazine if blood pressure still uncontrolled 1
4. Consider felodipine as alternative calcium channel blocker 1

Never use these agents in heart failure with reduced ejection fraction: 1

• Moxonidine (increased mortality) 1
• Alpha-adrenoceptor antagonists (cause fluid retention and worsen heart failure) 1
• Diltiazem or verapamil (negatively inotropic) 1

For Heart Failure Specifically

ACE inhibitors should be combined with: 1

• Beta-blockers (bisoprolol, carvedilol, or metoprolol succinate ER only—not a class effect) 1
• Diuretics for any fluid retention 1, 2
• MRA (spironolactone or eplerenone) if NYHA class II-IV with LVEF ≤35% 1, 2

Common Pitfalls to Avoid

Do not titrate based on blood pressure or symptom improvement alone—you must reach target doses because the mortality benefit is dose-dependent. 1 Studies show most patients receive suboptimal doses in clinical practice despite tolerating higher doses. 1

Do not discontinue ACE inhibitors for mild hypotension after the first dose—this is expected and can be managed by adjusting diuretic doses or temporarily reducing the ACE inhibitor dose, then resuming titration. 3, 4

Do not combine ACE inhibitors with potassium supplements or potassium-sparing diuretics during initial titration—wait until the ACE inhibitor dose is stable. 2, 4

If the patient develops intolerable cough (occurs in significant percentage of patients), switch to an ARB—but exercise extreme caution if the patient had angioedema with the ACE inhibitor, as angioedema can also occur with ARBs. 1, 2