What is the recommended dosage and administration of Perindopril (Angiotensin-Converting Enzyme inhibitor) for patients with hypertension or heart failure?

Perindopril Dosing and Administration

Stable Coronary Artery Disease

For patients with stable coronary artery disease, initiate perindopril at 4 mg once daily for 2 weeks, then increase to a maintenance dose of 8 mg once daily as tolerated. 1

• In elderly patients (>70 years), start with 2 mg once daily for the first week, increase to 4 mg once daily in the second week, then advance to 8 mg once daily for maintenance if tolerated 1
• This dosing strategy in the EUROPA trial demonstrated a 20% relative risk reduction in cardiovascular death, myocardial infarction, or cardiac arrest (target dose 8 mg/day) 2

Hypertension

For uncomplicated essential hypertension, start perindopril at 4 mg once daily and titrate upward to a maximum of 16 mg per day based on blood pressure control measured just before the next dose. 1

• The usual maintenance dose range is 4 to 8 mg administered as a single daily dose 1
• Perindopril may be administered in two divided doses; twice-daily regimens show slightly superior control (0.5-1.0 mmHg better) compared to once-daily dosing 1
• In elderly patients (>65 years), initiate at 4 mg daily in one or two divided doses; doses exceeding 8 mg should be administered with caution and close medical supervision 1

Combination with Diuretics

• If blood pressure is inadequately controlled with perindopril alone, 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 the diuretic cannot be discontinued, use an initial perindopril dose of 2-4 mg daily (in one or two divided doses) with careful medical supervision for several hours until blood pressure stabilizes 1
• Monitor closely for the first two weeks of treatment and whenever doses of perindopril and/or diuretics are increased 1

Heart Failure

While perindopril 4 mg once daily has been studied in heart failure with demonstrated improvements in exercise tolerance and symptoms, the evidence for heart failure with preserved ejection fraction (HF-PEF) remains inconclusive. 2, 3

• The PEP-CHF trial (Perindopril for Elderly People with Chronic Heart failure) showed no convincing reduction in morbidity and mortality in HF-PEF patients 2
• For symptomatic relief in heart failure, perindopril 4 mg once daily significantly improved hemodynamic parameters and exercise tolerance in mild to moderate CHF over 3 months 3
• Start with perindopril 2 mg to minimize first-dose hypotension, which occurs less frequently than with captopril, enalapril, or lisinopril at equivalent starting doses 3

Renal Impairment Considerations

Perindopril is contraindicated in patients with creatinine clearance <30 mL/min, as safety and efficacy have not been established in this population. 1

• Perindoprilat elimination is markedly decreased when creatinine clearance drops below 30 mL/min, leading to significant drug accumulation 1
• Dose reduction is required in patients with renal impairment 4

Monitoring Requirements

• Check blood pressure, renal function, and electrolytes at baseline, 1-2 weeks after each dose increment, at 3 months, and then every 6 months 2
• An increase in creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable 5
• If serum potassium rises to 5.0-5.5 mmol/L, reduce dose by 50%; discontinue if potassium exceeds 5.5 mmol/L 2

Important Caveats

• Avoid concomitant use with potassium-sparing diuretics during initiation 2
• Avoid NSAIDs and COX-2 inhibitors, which can reduce ACE inhibitor efficacy and worsen renal function 2
• Cough is the most common adverse event and the most frequent reason for treatment discontinuation 6
• Patients with multiple cardiovascular risk factors are more likely to require uptitration to the maximum dose (8 mg for hypertension) to achieve blood pressure control 7