What is the recommended dosage and treatment protocol for Perindopril (Angiotensin-Converting Enzyme Inhibitor) in managing 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 a target dose of 8 mg once daily, while for heart failure, it should be started at 2 mg once daily and gradually increased to 4 mg once daily. 1, 2

Dosing Recommendations for Hypertension

• Initial dose for uncomplicated hypertension is 4 mg once daily, which can be titrated upward until blood pressure is controlled or to a maximum of 16 mg per day 1
• Usual maintenance dose range is 4 to 8 mg administered as a single daily dose 1
• In elderly patients (>70 years), start with 2 mg once daily for the first week, followed by 4 mg once daily in the second week, and then 8 mg once daily for maintenance if tolerated 1
• For patients with concomitant diuretic therapy, if the diuretic cannot be discontinued 2-3 days prior to starting perindopril, use an initial dose of 2-4 mg daily with careful medical supervision 1

Dosing Recommendations for Heart Failure

• ACE inhibitors are recommended as first-line therapy in patients with reduced left ventricular systolic function (ejection fraction <40-45%) with or without symptoms 2
• For heart failure patients, perindopril should be initiated at a low dose (2 mg once daily) and gradually titrated upward 2, 3
• The target dose for perindopril in heart failure is 4 mg once daily, which has been shown to improve exercise tolerance and reduce symptoms in patients with mild to moderate heart failure 3
• Regular monitoring of renal function is recommended before, 1-2 weeks after each dose increment, and at 3-6 month intervals 2

Dose Adjustment in Special Populations

• In patients with renal impairment, perindopril elimination is decreased with marked accumulation when creatinine clearance drops below 30 mL/min 1
• In patients with creatinine clearance <30 mL/min, safety and efficacy of perindopril have not been established 1
• For patients with stable coronary artery disease, perindopril should be given at an initial dose of 4 mg once daily for 2 weeks, then increased to a maintenance dose of 8 mg once daily 1

Clinical Evidence Supporting Efficacy

• In the EUROPA trial, perindopril therapy (target dose 8 mg/day) was associated with a 20% relative risk reduction in the primary endpoint of cardiovascular death, MI, or cardiac arrest (p<0.003) 2
• The benefit of perindopril treatment was similar for patients with or without hypertension, with a mean reduction in blood pressure of 5/2 mmHg 2
• Perindopril 4 mg significantly improved haemodynamic parameters in both short-term and long-term studies involving patients with congestive heart failure 3

Monitoring and Follow-up

• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, and subsequently at regular 6-month intervals 2
• If renal function deteriorates substantially, stop treatment 2
• Avoid potassium-sparing diuretics during initiation of therapy 2
• Avoid NSAIDs and COX-2 inhibitors as they may reduce the effectiveness of perindopril 2

Common Adverse Effects and Management

• Cough is the most common adverse event reported during treatment with perindopril, and is also the most common reason for treatment withdrawal 4
• If a troublesome cough develops that can be proven to be due to ACE inhibition, substitution of an angiotensin receptor blocker can be considered 2
• Some rise in urea, creatinine, and potassium is expected after starting an ACE inhibitor; if the increase is small and asymptomatic, no action is necessary 2
• An increase in creatinine of up to 50% above baseline or to 266 μmol/L (3 mg/dL), whichever is smaller, is acceptable 2

Important Precautions

• ACE inhibitors should be given as the initial therapy in the absence of fluid retention. In patients with fluid retention, ACE inhibitors should be given together with diuretics 2
• Avoid excessive diuresis before treatment; consider reducing or withholding diuretics for 24 hours before initiating perindopril 2
• If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to >310 μmol/L, the ACE inhibitor should be stopped and specialist advice sought 2

Perindopril is a well-tolerated ACE inhibitor that has been shown to be effective in both hypertension and heart failure, with additional benefits in reducing cardiovascular events in patients with stable coronary artery disease 4, 3.