What is the recommended dosing for perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor) in treating hypertension and heart failure?

Perindopril Dosing for Hypertension and Heart Failure

For hypertension, perindopril should be initiated at 4 mg once daily and titrated up to 8 mg once daily as needed, while for heart failure, treatment should begin at 2 mg once daily and gradually increase to a target dose of 4-8 mg once daily based on tolerability.

Dosing for Hypertension

Initial Dosing

• Standard initial dose: 4 mg once daily 1
• Elderly patients (>65 years): 4 mg once daily, with more caution needed for doses exceeding 8 mg 1
• Very elderly patients (>70 years): 2 mg once daily for the first week, then 4 mg once daily in the second week 1
• Patients with renal impairment (CrCl <30 mL/min): Safety and efficacy not established, dose adjustment required 1

Maintenance and Titration

• Usual maintenance dose: 4-8 mg once daily 1
• Maximum dose: 16 mg per day 1
• Titration: Increase dose until blood pressure is controlled when measured just before the next dose 1
• Administration options: Can be given as a single daily dose or in two divided doses 1

Special Considerations

• Concomitant diuretic use: If possible, discontinue diuretic 2-3 days before starting perindopril to reduce risk of symptomatic hypotension 1
• If diuretic cannot be discontinued: Start with 2-4 mg daily (single or divided doses) with careful monitoring 1

Dosing for Heart Failure

Initial and Target Dosing

• Initial dose: 2 mg once daily 2, 3
• Target dose: 4-8 mg once daily 2, 3
• Titration: Increase gradually based on tolerability 3

Evidence Supporting Efficacy

Hypertension

• Perindopril 4-8 mg once daily significantly reduces systolic and diastolic blood pressure with effects maintained for at least 24 hours 4
• Response rates with perindopril 4-8 mg once daily (67-80%) were significantly higher than with captopril 25-50 mg twice daily (44-57%) 4
• The PEACH study demonstrated that perindopril, uptitrated to 8 mg as needed, significantly reduced blood pressure in patients with mild-to-moderate hypertension and additional cardiovascular risk factors 5

Heart Failure

• Perindopril 4 mg significantly improved hemodynamic parameters in patients with congestive heart failure in both short-term and long-term studies 3
• Treatment with perindopril 4 mg once daily significantly increased exercise tolerance and reduced symptoms in patients with mild to moderate heart failure 3
• The ADVANCE trial showed that perindopril combined with indapamide reduced cardiovascular events in patients with type 2 diabetes 2

Clinical Pearls and Precautions

Blood Pressure Targets

• For patients with diabetes and hypertension: <130/80 mmHg 2
• For patients with increased cardiovascular risk: <130/80 mmHg 2

Monitoring

• Monitor blood pressure, renal function, and potassium levels before initiating therapy and periodically thereafter 2
• Check blood chemistry 1-2 weeks after initiation and after final dose titration 2

Common Adverse Effects

• Cough is the most common adverse effect (reported in up to 20% of patients) 2, 3
• First-dose hypotension, especially in volume-depleted patients 1
• Angioedema occurs in <1% of patients but is more frequent in Black patients 2

Contraindications

• History of angioedema related to previous ACE inhibitor therapy 6
• Pregnancy (second and third trimesters) 2

Special Populations

Elderly Patients

• Start with lower doses (2 mg once daily) in very elderly patients (>70 years) 1
• Titrate more cautiously with close monitoring 1

Renal Impairment

• Perindoprilat elimination is decreased in renally impaired patients 1
• Marked accumulation occurs when creatinine clearance drops below 30 mL/min 1
• Safety and efficacy not established in patients with CrCl <30 mL/min 1

By following these dosing recommendations and monitoring guidelines, perindopril can be effectively and safely used to treat both hypertension and heart failure, with demonstrated benefits in reducing cardiovascular events and improving symptoms.