What is the recommended dosage and treatment protocol for perindopril (angiotensin-converting enzyme inhibitor) in managing hypertension and heart failure?

Perindopril Dosing and Treatment Protocol

For hypertension, initiate perindopril at 4 mg once daily and titrate to a maintenance dose of 4-8 mg daily; for stable coronary artery disease, start at 4 mg daily for 2 weeks then increase to 8 mg daily as tolerated. 1

Hypertension Management

Initial Dosing Strategy

• Start with 4 mg once daily in uncomplicated hypertensive patients 1
• Measure blood pressure just before the next dose to assess control 1
• Titrate upward until blood pressure is controlled or to a maximum of 16 mg per day 1
• The usual maintenance dose range is 4-8 mg administered as a single daily dose 1

Elderly Patients (>65 years)

• Begin with the same 4 mg daily dose as younger patients, given in one or two divided doses 1
• Exercise caution with doses exceeding 8 mg in elderly patients, as clinical experience is limited above this threshold 1
• Doses above 8 mg should be administered under close medical supervision 1

Combination with Diuretics

• If blood pressure remains uncontrolled on perindopril monotherapy, add a diuretic 1
• In patients currently on diuretics, discontinue the diuretic 2-3 days before starting perindopril to reduce risk of symptomatic hypotension 1
• If diuretic cannot be discontinued, use an initial dose of 2-4 mg daily with careful medical supervision for several hours until blood pressure stabilizes 1
• Follow the patient closely for the first two weeks and whenever doses are increased 1

Stable Coronary Artery Disease

Standard Dosing Protocol

• Initial dose: 4 mg once daily for 2 weeks 1
• Maintenance dose: 8 mg once daily if tolerated 1

Elderly Patients (>70 years) with CAD

• Week 1: 2 mg once daily 1
• Week 2: 4 mg once daily 1
• Maintenance: 8 mg once daily if tolerated 1

Heart Failure Management

Dosing Considerations

• While perindopril is not specifically listed in the European Society of Cardiology's recommended ACE inhibitor maintenance doses for heart failure, the general ACE inhibitor principles apply 2
• Start with low doses and uptitrate to target doses proven effective in large trials, not based on symptomatic improvement alone 2
• Perindopril 4 mg once daily has demonstrated efficacy in improving exercise tolerance and reducing heart failure symptoms in mild to moderate CHF 3

Initiation Protocol for Heart Failure

• Review and potentially reduce diuretic doses before starting to avoid excessive diuresis 2
• Consider starting treatment in the evening when supine to minimize hypotensive effects, though evidence specific to heart failure is limited 2
• Avoid potassium-sparing diuretics during initiation 2
• Always administer in combination with diuretics if fluid retention is present 2

Monitoring Requirements

Timing of Laboratory Checks

• Check blood pressure, renal function (creatinine), and electrolytes (potassium) 1-2 weeks after each dose increment 2
• Recheck at 3 months, then at 6-month intervals 2
• More frequent monitoring is required in patients with pre-existing renal dysfunction or electrolyte disturbances 2

Acceptable Changes After Initiation

• Creatinine increase up to 50% above baseline or to 266 μmol/L (3 mg/dL) is acceptable 2
• Potassium increase to ≤5.5 mmol/L is acceptable 2
• If creatinine rises >100% or to >310 μmol/L (3.5 mg/dL), or potassium rises >5.5 mmol/L, stop the medication and seek specialist advice 2

Important Clinical Pitfalls

Medications to Avoid

• NSAIDs and COX-2 inhibitors should be avoided as they can worsen renal function and reduce antihypertensive efficacy 2
• Avoid potassium supplements and potassium-sparing diuretics (triamterene, amiloride) during initiation to prevent hyperkalemia 2

Managing Hypotension

• Asymptomatic low blood pressure does not require treatment discontinuation 2
• If symptomatic hypotension occurs, review and reduce doses of other vasodilators and consider reducing diuretic dose if no signs of congestion 2

Cough Management

• Cough is common but rarely requires discontinuation 2
• Only switch to an angiotensin receptor blocker if cough is severe enough to stop the patient from sleeping and can be proven due to ACE inhibition through withdrawal and rechallenge 2

Comparative Effectiveness

Evidence from Clinical Trials

• Perindopril 4-8 mg once daily produces response rates of 67-80% (defined as diastolic BP ≤90 mmHg), significantly higher than captopril 25-50 mg twice daily (44-57%) 4
• The antihypertensive effects are similar to other ACE inhibitors including enalapril and calcium-channel antagonists 4
• Patients with more cardiovascular risk factors require higher doses to achieve blood pressure control 5