What is the effect of Perindopril (Angiotensin-Converting Enzyme Inhibitor)?

From the Guidelines

Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to reduce the risk of cardiovascular events, including cardiovascular death, myocardial infarction, and stroke, by 20% in patients with stable coronary artery disease, as demonstrated in the EUROPA trial 1. The EUROPA trial, which included 12,218 patients, found that perindopril therapy, with a target dose of 8 mg/d, was associated with a significant reduction in the primary end point of cardiovascular death, MI, or cardiac arrest, compared to placebo 1. Key benefits of perindopril include:

• Reduction in cardiovascular events, including cardiovascular death, myocardial infarction, and stroke
• Decrease in blood pressure, with a mean reduction of 5/2 mm Hg
• Improvement in outcomes for patients with stable coronary artery disease, regardless of hypertension status
• Potential to reduce the incidence of revascularization, cardiac arrest, heart failure, worsening angina, and all-cause mortality It is essential to note that perindopril should be used with caution in patients with kidney impairment or those taking potassium supplements, as it can increase the risk of hyperkalemia 1. In terms of dosing, the typical starting dose of perindopril is 4 mg once daily, which may be increased to 8 mg daily if needed for blood pressure control, as seen in the EUROPA trial 1. Overall, perindopril is a valuable medication for reducing the risk of cardiovascular events in patients with stable coronary artery disease, and its use should be considered in accordance with the latest clinical guidelines and patient-specific factors.

From the FDA Drug Label

The mechanism through which perindoprilat lowers blood pressure is believed to be primarily inhibition of ACE activity ACE is a peptidyl dipeptidase that catalyzes conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion.

The effect of Perindopril, an Angiotensin-Converting Enzyme (ACE) Inhibitor, is to:

• Decrease vasoconstriction by inhibiting the conversion of angiotensin I to angiotensin II
• Increase plasma renin activity
• Decrease aldosterone secretion, resulting in diuresis and natriuresis and a possible small increase in serum potassium
• Lower blood pressure by reducing peripheral resistance with no significant changes in heart rate or glomerular filtration rate 2, 2, 2

From the Research

Effects of Perindopril on Blood Pressure

• Perindopril is a long-acting angiotensin-converting enzyme (ACE) inhibitor that significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients 3, 4.
• The antihypertensive efficacy of 4 and 8 mg doses is significantly greater than that of 2 mg or of placebo, with a maximal response attained about 4 to 6 h after the first dose 5.
• Perindopril 4 to 8 mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension, with adequate diastolic blood pressure control attained in about 60 to 70% of patients with monotherapy 3, 5.

Effects of Perindopril on Vascular Abnormalities

• Perindopril treatment improves or normalises vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy 4.
• Perindopril significantly decreases carotid-femoral aortic pulse wave velocity (PWV) and improves arterial compliance 4.
• Perindopril also reduces left ventricular mass index and preserves cerebral blood flow despite significantly reducing SBP and DBP in patients with recent cerebral ischaemia and/or stroke 4.

Effects of Perindopril on Congestive Heart Failure

• Perindopril is a long-acting ACE inhibitor that inhibits the renin-angiotensin system, reducing vasoconstriction and left ventricular remodelling characteristic of heart failure 6.
• Perindopril 4mg significantly improves haemodynamic parameters and increases exercise tolerance in patients with mild to moderate congestive heart failure (CHF) 6.
• Perindopril 4mg once daily is generally well tolerated in patients with mild to moderate CHF, with a low incidence of adverse events, including cough, which led to 2.8% of patients discontinuing treatment 6.

Comparison with Other ACE Inhibitors

• Perindopril has a similar adverse event profile to that of other ACE inhibitors, with cough being the most common event reported during treatment 4.
• Perindopril is at least as effective as usual therapeutic doses of captopril, atenolol, or a combination of hydrochlorothiazide plus amiloride in mild to moderate essential hypertension 3, 5.
• Perindopril has a higher response rate than captopril in the treatment of hypertension, with 67 to 80% of patients achieving supine DBP < or = 90 mm Hg compared to 44 to 57% with captopril 4.