What is the recommended dose of Ramipril (Angiotensin-Converting Enzyme (ACE) inhibitor) for adults with hypertension or heart failure?

Ramipril Dosing for Hypertension and Heart Failure

Hypertension Dosing

For hypertension, start ramipril at 2.5 mg once daily and titrate to a usual maintenance range of 2.5-20 mg daily, administered as a single dose or divided twice daily. 1

• The FDA-approved initial dose is 2.5 mg once daily for patients not receiving a diuretic 1
• Adjust dosing based on blood pressure response, with the maintenance range typically between 2.5-20 mg per day 1
• If the antihypertensive effect diminishes toward the end of the dosing interval with once-daily administration, consider increasing the dose or switching to twice-daily dosing 1
• If blood pressure remains uncontrolled on ramipril alone, add a diuretic 1
• Clinical trial data demonstrate that 41% of hypertensive patients required only 2.5 mg daily and 81% required ≤5 mg daily for adequate control 2
• The 2024 ESC guidelines recommend ACE inhibitors like ramipril as first-line therapy for hypertension, preferably in combination with a dihydropyridine calcium channel blocker or diuretic 3

Heart Failure Post-Myocardial Infarction Dosing

For heart failure post-MI, start ramipril at 2.5 mg twice daily (or 1.25 mg twice daily if hypotensive) and titrate toward a target dose of 5 mg twice daily (10 mg total daily). 1

• The recommended starting dose is 2.5 mg twice daily (5 mg per day total) 1
• Patients who become hypotensive at the initial dose should be switched to 1.25 mg twice daily 1
• After one week at the starting dose, increase the dose (if tolerated) toward the target of 5 mg twice daily, with dosage increases spaced approximately 3 weeks apart 1
• This target dose of 5 mg twice daily was used in the AIRE trial and demonstrated a 27% reduction in relative mortality risk 3, 4
• The ACC/AHA guidelines list ramipril with an initial dose of 1.25-2.5 mg once daily and a maximum dose of 10 mg once daily for heart failure 3

Critical Monitoring and Safety Protocols

After the initial dose, observe patients for at least 2 hours and until blood pressure stabilizes for an additional hour. 1

• Establish baseline renal function, potassium, and blood pressure before initiating therapy 1
• Check serum potassium and creatinine after 5-7 days of initiation or dose changes 4
• Consider reducing or withholding diuretics for 24 hours before the first dose if volume depletion is suspected 5
• Creatinine increases up to 50% above baseline or to 3 mg/dL (whichever is greater) are acceptable during titration 5
• If creatinine rises by 100% or exceeds 4 mg/dL, halve the dose and seek specialist advice 5
• Asymptomatic hypotension does not require dose adjustment, but hypotension after the initial dose does not preclude careful subsequent titration 1

Dosing Adjustments for Renal Impairment

For patients with creatinine clearance <40 mL/min, start with 1.25 mg once daily and titrate cautiously. 1

• In hypertension with renal impairment, the initial dose is 1.25 mg once daily, with a maximum total daily dose of 5 mg 1
• In heart failure with renal impairment, start at 1.25 mg once daily, increase to 1.25 mg twice daily, and titrate to a maximum of 2.5 mg twice daily based on response and tolerability 1
• For creatinine clearance >40 mL/min, usual dosing regimens can be followed 1

Special Populations and Circumstances

For volume-depleted patients or those with suspected renal artery stenosis, initiate ramipril at 1.25 mg once daily. 1

• Volume depletion (from current or past diuretic use) increases the risk of hypotension 1
• Adjust dosage according to blood pressure response in these high-risk patients 1

Critical Drug Interactions to Avoid

Do not combine ramipril with NSAIDs, COX-2 inhibitors, potassium supplements, potassium salt substitutes, or potassium-sparing diuretics unless absolutely necessary. 5, 1

• NSAIDs and COX-2 inhibitors can worsen renal function and reduce ACE inhibitor efficacy 5
• Concomitant use of potassium-sparing agents can lead to dangerous hyperkalemia 1
• Do not combine two RAS blockers (ACE inhibitor plus ARB) as this is not recommended 3

Common Pitfalls to Avoid

Do not discontinue ramipril for small creatinine rises, as clinical deterioration is likely if withdrawn. 5

• Undertitration is a major problem—higher doses provide superior outcomes, so push toward target doses 5
• The appearance of hypotension after the initial dose does not preclude subsequent careful titration 1
• Persistent cough should be tolerated if not severe, given the long-term mortality benefits 3
• Maintain ramipril lifelong, even beyond age 85, if well tolerated 3