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

From the Guidelines

Ramipril is recommended as a first-line treatment for patients with hypertension, heart failure, and peripheral artery disease, due to its ability to reduce morbidity and mortality, as shown in the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline 1.

Key Points

• Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that works by blocking the conversion of angiotensin I to angiotensin II, reducing blood vessel constriction and decreasing blood pressure.
• The typical starting dose is 2.5 mg once daily, which can be gradually increased to a maintenance dose of 5-10 mg daily based on blood pressure response.
• Ramipril has been shown to reduce the risk of cardiovascular events, including stroke, myocardial infarction, and heart failure, in high-risk patients, as demonstrated in the HOPE trial 1.
• The use of ACE inhibitors, such as ramipril, is recommended for patients with peripheral artery disease (PAD) and hypertension, as they have been shown to reduce the risk of major adverse cardiovascular events (MACE) and improve symptoms of claudication, as stated in the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline 1.

Benefits and Risks

• Benefits: reduced morbidity and mortality, improved symptoms of claudication, and reduced risk of MACE.
• Risks: dry cough, dizziness, headache, angioedema, and hyperkalemia.

Monitoring and Contraindications

• Blood pressure, kidney function, and potassium levels should be monitored regularly during treatment.
• Ramipril is contraindicated during pregnancy and should be used cautiously in patients with kidney disease or those taking potassium supplements.

Comparison with Other Treatments

• Ramipril has been shown to be effective in reducing cardiovascular events, similar to other ACE inhibitors and angiotensin-receptor blockers, as demonstrated in the ONTARGET trial 1.
• The choice of antihypertensive medication should be individualized based on patient characteristics and comorbidities, as recommended in the 2017 ACC/AHA hypertension clinical practice guideline 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Ramipril and ramiprilat inhibit ACE in human subjects and animals. Angiotensin converting enzyme is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium In hypertensive patients with normal renal function treated with ramipril alone for up to 56 weeks, approximately 4% of patients during the trial had an abnormally high serum potassium and an increase from baseline greater than 0.75 mEq/L, and none of the patients had an abnormally low potassium and a decrease from baseline greater than 0. 75 mEq/L.

The main mechanism of action of Ramipril is the inhibition of ACE, which leads to decreased plasma angiotensin II and subsequently decreased aldosterone secretion. This may result in a small increase of serum potassium.

• Key effects of Ramipril include:
  • Decreased vasopressor activity
  • Decreased aldosterone secretion
  • Potential small increase in serum potassium
• Important consideration: Approximately 4% of patients treated with Ramipril alone had abnormally high serum potassium and an increase from baseline greater than 0.75 mEq/L 2

From the Research

Overview of Ramipril

• Ramipril is a long-acting angiotensin converting enzyme (ACE) inhibitor, which exhibits similar pharmacodynamic properties to captopril and enalapril 3.
• It is a prodrug, hydrolysed after absorption to form the active metabolite ramiprilat, which has a long elimination half-life, permitting once daily administration 3, 4.

Therapeutic Use

• Ramipril is indicated in the treatment of hypertension, congestive cardiac failure, nephropathy, and prevention of cardiovascular events in high risk individuals 5.
• The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies and comparative trials, with approximately 85% of patients with mild to moderate essential hypertension responding successfully to treatment 4.
• Ramipril is also effective in patients with diabetes mellitus, decreasing urinary albumin excretion in diabetic patients with nephropathy 4.

Comparison with Other ACE Inhibitors

• Ramipril shows comparable antihypertensive efficacy to usual therapeutic dosages of captopril, enalapril, and atenolol in patients with mild to moderate essential hypertension 3.
• However, a review of ACE inhibitors and angiotensin receptor blockers (ARBs) found no difference in efficacy between the two, but ACE inhibitors are associated with a higher risk of adverse events such as cough and angioedema 6.

Adverse Effects and Tolerability

• Ramipril is well tolerated, with 5% or fewer patients discontinuing therapy because of drug intolerance 4.
• The adverse effect profile of ramipril is typical of ACE inhibitors as a class, with a low risk of angioedema and fatalities 3, 6.