What is the recommended dose of Perindopril (Angiotensin-Converting Enzyme inhibitor) for treating hypertension and heart failure?

Perindopril Dosing for Hypertension and Heart Failure

For hypertension, start perindopril at 4 mg once daily and titrate to a maintenance dose of 4-8 mg daily, with a maximum of 16 mg daily if needed; for stable coronary artery disease, start at 4 mg daily for 2 weeks then increase to 8 mg daily; for heart failure with reduced ejection fraction, start at 2 mg daily and titrate to a target dose of 8-16 mg daily. 1

Hypertension Dosing

Standard Adult Dosing

• Initial dose: 4 mg once daily 1
• Maintenance dose: 4-8 mg once daily (usual range) 1
• Maximum dose: 16 mg daily 1
• Titration: Increase dosage upward until blood pressure measured just before the next dose is controlled 1
• Alternative regimen: May be administered in two divided doses, which provides slightly superior control (approximately 0.5-1.0 mmHg better) than once-daily dosing 1

Elderly Patients (>65 years)

• Initial dose: 4 mg daily in one or two divided doses 1
• Maximum dose: 8 mg daily (experience is limited above this dose) 1
• Caution: Doses above 8 mg should be administered with close medical supervision 1
• Very elderly (>70 years) with coronary disease: Start at 2 mg daily for week 1, then 4 mg daily for week 2, then 8 mg daily for maintenance if tolerated 1

Concomitant Diuretic Use

• If possible: Discontinue diuretic 2-3 days before starting perindopril to reduce risk of symptomatic hypotension 1
• If diuretic cannot be stopped: Start perindopril at 2-4 mg daily in one or two divided doses with careful medical supervision for several hours until blood pressure stabilizes 1
• Monitoring: Follow closely for the first two weeks and whenever doses are increased 1

Stable Coronary Artery Disease Dosing

• Initial dose: 4 mg once daily for 2 weeks 1
• Target maintenance dose: 8 mg once daily 1, 2
• Titration: Increase as tolerated after the initial 2-week period 1
• Evidence base: The EUROPA trial demonstrated that perindopril 8 mg daily reduced cardiovascular death, MI, or cardiac arrest by 20% over 4.2 years 2

Heart Failure with Reduced Ejection Fraction (HFrEF) Dosing

Target Doses from Guidelines

• Initial dose: 2 mg once daily 2
• Target dose: 8-16 mg once daily 2
• Minimum effective target: At least 50% of target dose (4 mg daily) should be achieved 2
• Titration strategy: Increase dose gradually, reassessing blood pressure, renal function, and potassium within 1-2 weeks after each dose increment 2

Clinical Trial Dosing

• PROGRESS trial: Started at 4 mg perindopril daily (combined with indapamide) 2
• ADVANCE trial: Started at 2 mg daily, increased to 4 mg daily after 3 months (combined with indapamide) 2

Renal Impairment Dosing

• Creatinine clearance >30 mL/min: Initial dose 2 mg daily, maximum 8 mg daily 1
• Creatinine clearance <30 mL/min: Safety and efficacy not established; use not recommended 1
• Dialysis: Perindopril is removed during dialysis with the same clearance as in patients with normal renal function 1

Key Monitoring Parameters

• Before initiation: Blood pressure (including postural changes), renal function, and potassium 2
• After dose changes: Reassess within 1-2 weeks 2
• Ongoing: Monitor at 3-6 month intervals during chronic therapy 3
• First-dose observation: Close monitoring for several hours after initial dose, especially in patients on diuretics or with volume depletion 1

Common Pitfalls to Avoid

• Underdosing in HFrEF: Clinical trials designed to evaluate survival increased doses to predetermined targets rather than stopping at symptom relief; aim for target doses of 8-16 mg daily 2
• Premature discontinuation for cough: While cough is the most common adverse event, it only leads to discontinuation in approximately 2.8% of patients 4
• Inadequate monitoring: Failure to check renal function and potassium 1-2 weeks after initiation or dose increases can miss important adverse effects 2
• Stopping diuretics unnecessarily: If hypotension occurs after first dose, this does not preclude subsequent careful titration after managing the hypotension 1

Absolute Contraindications Requiring Discontinuation

• Angioedema during therapy (occurs in <1% of patients, more common in Black patients) 2, 3
• Bilateral renal artery stenosis 3
• Pregnancy 3

Duration of Therapy

• Hypertension and cardiovascular prevention: Continue as chronic therapy without predetermined endpoint 3
• Post-myocardial infarction: Reasonable to continue beyond 3 years as long-term treatment 3
• Long-term benefits: Early initiation with 10-year continuation showed 93% survival versus 66% in those starting 3 years later (27% absolute risk reduction) 3