Ramipril

• Hypertension
• Heart Failure
• Cardiovascular Risk Reduction
• Post-Myocardial Infarction

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension, heart failure, and reduce cardiovascular risk in high-risk patients. It has demonstrated significant mortality benefits in clinical trials.

Mechanism of Action

Ramipril is a prodrug converted to its active form, ramiprilat:

• ACE inhibition: Blocks conversion of angiotensin I to angiotensin II
• Reduces vasoconstriction: Angiotensin II is a potent vasoconstrictor
• Decreases aldosterone: Reduces sodium and water retention
• Increases bradykinin: May contribute to vasodilation (and cough side effect)
• Cardioprotective effects: Reduces cardiac remodeling and fibrosis

These mechanisms result in lowered blood pressure and reduced cardiac workload.

Available Formulations

Ramipril is available as oral capsules:

• 1.25 mg, 2.5 mg, 5 mg, 10 mg

Capsule contents can be mixed with water, apple juice, or applesauce for easier administration.

Medical Uses

FDA-Approved Indications:

• Hypertension (alone or with other antihypertensives)
• Heart failure post-myocardial infarction
• Reduction in risk of myocardial infarction, stroke, and death from cardiovascular causes in patients ≥55 years at high risk for cardiovascular events

The HOPE trial demonstrated significant cardiovascular mortality reduction in high-risk patients.

Dosing Guidelines

Hypertension:

• Initial: 2.5 mg once daily
• Maintenance: 2.5-20 mg daily (once daily or divided twice daily)
• Maximum: 20 mg/day

Heart Failure Post-MI:

• Initial: 2.5 mg twice daily (may start with 1.25 mg if hypotension risk)
• Target: 5 mg twice daily

Cardiovascular Risk Reduction:

• Initial: 2.5 mg once daily for 1 week, then 5 mg daily for 3 weeks
• Maintenance: 10 mg once daily

Renal Impairment:

• CrCl <40 mL/min: Start with 1.25 mg daily; maximum 5 mg daily

Important Safety Information

Black Box Warning:

• Fetal toxicity: Can cause fetal harm when administered during pregnancy. Discontinue as soon as pregnancy is detected.

Contraindications:

• History of angioedema related to previous ACE inhibitor treatment
• Hereditary or idiopathic angioedema
• Concomitant use with aliskiren in patients with diabetes
• Pregnancy

Warnings and Precautions:

• Angioedema: Can occur at any time; more common in Black patients
• Hypotension: Risk with volume depletion, diuretics, or heart failure
• Hyperkalemia: Monitor potassium, especially with renal impairment
• Renal impairment: Monitor renal function; may cause acute renal failure
• Cough: Dry, nonproductive cough is common

Drug Interactions

• Potassium-sparing diuretics, potassium supplements: Increased hyperkalemia risk
• NSAIDs: May reduce antihypertensive effect; increase renal dysfunction risk
• Lithium: Increased lithium levels; monitor lithium
• Diuretics: Increased hypotension risk
• Aliskiren: Contraindicated in diabetics; avoid in renal impairment
• mTOR inhibitors (sirolimus, everolimus, temsirolimus): Increased angioedema risk

Special Populations

• Hepatic Impairment: May have decreased conversion to active metabolite; start with lower doses
• Renal Impairment: Reduce starting dose and maximum dose
• Pregnancy: Contraindicated (Category D)
• Lactation: Present in breast milk; not recommended
• Elderly: Start with lower doses; may have exaggerated response
• Pediatric: Safety and efficacy not established