What are the initial and maximum dosages for Angiotensin-Converting Enzyme (ACE) inhibitors, such as lisinopril, and Angiotensin Receptor Blockers (ARBs), such as losartan, in a patient with hypertension and potential impaired renal function?

ACE Inhibitor and ARB Dosing Guidelines

For hypertension with potential renal impairment, start lisinopril at 2.5-5 mg once daily (2.5 mg if creatinine clearance ≤30 mL/min) and titrate to a target of 20-40 mg daily; for losartan, start at 25-50 mg once daily (25 mg if volume depleted or hepatic impairment) and titrate to 100 mg daily. 1, 2

ACE Inhibitor Dosing: Lisinopril as Prototype

Initial Dosing

• Standard starting dose: 5 mg once daily for most patients with hypertension 1
• Renal impairment adjustments: 1
  • Creatinine clearance >30 mL/min: No adjustment needed, start at 5 mg
  • Creatinine clearance 10-30 mL/min: Start at 2.5 mg once daily (half the usual dose)
  • Creatinine clearance <10 mL/min or hemodialysis: Start at 2.5 mg once daily
• Heart failure: Start at 2.5 mg once daily if hyponatremia present (serum sodium <130 mEq/L), otherwise 5 mg once daily 1

Target/Maximum Dosing

• Maximum dose: 40 mg once daily across all indications 1
• Heart failure target: Titrate to 40 mg once daily as tolerated 3
• Hypertension target: 20-40 mg once daily 3
• Post-MI: 10 mg once daily (after initial titration from 5 mg) 3

Titration Strategy

• Increase doses gradually, doubling at intervals as tolerated 3
• Monitor renal function and potassium within 1-2 weeks after initiation or dose changes 3
• Accept up to 30% increase in serum creatinine as expected pharmacologic effect 4

ARB Dosing: Losartan as Prototype

Initial Dosing

• Standard starting dose: 50 mg once daily for hypertension 2
• Volume depletion: 25 mg once daily if on diuretics or possible intravascular depletion 2
• Hepatic impairment: 25 mg once daily for mild-to-moderate impairment 2
• Heart failure: Start at 25-50 mg once daily 3

Target/Maximum Dosing

• Hypertension maximum: 100 mg once daily 2
• Heart failure target: 100-150 mg once daily for optimal outcomes 5
  • The HEAAL trial demonstrated 150 mg daily was superior to 50 mg daily with 10% relative risk reduction in death or HF hospitalization 5
  • European Society of Cardiology recommends 150 mg as target dose for heart failure 5
• Diabetic nephropathy: Titrate to 100 mg once daily 2, 4

Titration Strategy

• Adjust doses no more frequently than every 2 weeks 5
• For heart failure with low baseline blood pressure, titrate weekly with small increments 5
• Monitor serum creatinine/eGFR and potassium within 1-2 weeks after initiation 3, 4

Additional ACE Inhibitor Examples

Captopril

• Initial: 6.25-12.5 mg three times daily 3
• Target: 25-50 mg three times daily 3
• Mean dose achieved in trials: 122.7 mg/day 3

Enalapril

• Initial: 2.5 mg twice daily 3
• Target: 10-20 mg twice daily 3
• Mean dose achieved in trials: 16.6 mg/day 3

Ramipril

• Initial: 1.25-2.5 mg once daily 3
• Target: 10 mg once daily 3

Trandolapril

• Initial: 0.5-1 mg once daily 3
• Target: 4 mg once daily 3

Additional ARB Examples

Valsartan

• Initial: 20-40 mg twice daily 3
• Target: 160 mg twice daily 3
• Mean dose achieved in trials: 254 mg/day 3
• Post-MI: Start at 20 mg twice daily, titrate to 160 mg twice daily 3

Candesartan

• Initial: 4-8 mg once daily 3
• Target: 32 mg once daily 3
• Mean dose achieved in trials: 24 mg/day 3

Critical Monitoring Parameters

Renal Function

• Check serum creatinine and eGFR within 1-2 weeks of initiation or dose changes 3
• Continue therapy even if creatinine increases up to 30% within 4 weeks 4
• Monitor at least annually during maintenance therapy 3

Electrolytes

• Check potassium within 1-2 weeks of initiation or dose changes 3
• Particular caution with baseline potassium >5.0 mEq/L 3
• Higher risk with diabetes, renal impairment, or concomitant potassium-sparing agents 3

Blood Pressure

• Monitor for hypotension, especially in volume-depleted patients 3
• Caution with systolic BP <80 mm Hg 3
• Check both sitting and standing BP due to postural hypotension risk 5

Critical Contraindications and Cautions

Absolute Contraindications

• History of angioedema with ACE inhibitors or ARBs 3
• Pregnancy or planning pregnancy 3
• Bilateral renal artery stenosis 3

Relative Contraindications

• Serum creatinine >3 mg/dL (use with caution, not absolute contraindication) 3
• Systolic BP <80 mm Hg 3
• Hyperkalemia >5.0 mEq/L 3

Dangerous Drug Combinations

• Never combine ACE inhibitor + ARB + aldosterone antagonist: Potentially harmful with increased risk of hyperkalemia, syncope, and acute kidney injury 3
• Never combine ACE inhibitor + ARB: No added cardiovascular benefit with increased adverse events 3
• Never combine with direct renin inhibitors: Increased risk of hyperkalemia and renal dysfunction 3

Common Pitfalls to Avoid

Underdosing

• Less than 25% of patients are titrated to target doses in clinical practice 5
• Use evidence-based target doses: The mortality and morbidity benefits demonstrated in trials were achieved at target doses, not lower doses 3, 5
• For losartan in heart failure, 50 mg daily appears inferior to ACE inhibitors; aim for 100-150 mg daily 5

Premature Discontinuation

• Don't stop for mild creatinine increases (<30%): This is an expected pharmacologic effect, not harm 4
• Don't discontinue immediately for hyperkalemia: Manage potassium medically before reducing or stopping therapy 4
• Continue even when eGFR falls below 30 mL/min/1.73 m² unless symptomatic hypotension or uncontrolled hyperkalemia develops 4

Inadequate Monitoring

• Failure to check renal function and potassium within 1-2 weeks of initiation is a common error 3
• Must monitor at least annually during maintenance 3