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

For hypertension, start ramipril at 2.5 mg once daily and titrate to a maintenance dose of 2.5-20 mg daily (typically 2.5-10 mg), while for heart failure post-MI, start at 2.5 mg twice daily and titrate to a target of 5 mg twice daily. 1

Hypertension Dosing

Initial and Maintenance Therapy:

• Start with 2.5 mg once daily in patients not on diuretics 1
• Titrate according to blood pressure response to usual maintenance range of 2.5-20 mg daily, given as a single dose or divided twice daily 1
• Most patients achieve control with 2.5-5 mg once daily—in a large prospective study, 41% required only 2.5 mg and 81% required ≤5 mg once daily 2
• If antihypertensive effect diminishes toward end of dosing interval, increase dose or switch to twice-daily administration 1
• Add a diuretic if blood pressure remains uncontrolled on ramipril alone 1

Renal Impairment Adjustments:

• For creatinine clearance >40 mL/min: use usual dosing 1
• For creatinine clearance <40 mL/min: start at 1.25 mg once daily, titrate to maximum of 5 mg daily 1

Volume Depletion or Renal Artery Stenosis:

• Initiate at 1.25 mg once daily if volume depletion or renal artery stenosis is suspected 1

Heart Failure Post-Myocardial Infarction Dosing

Initiation and Titration:

• Start at 2.5 mg twice daily (5 mg/day total) 1
• If hypotension occurs, reduce to 1.25 mg twice daily 1
• After one week, titrate toward target dose of 5 mg twice daily, with dose increases approximately 3 weeks apart 1
• Observe patient under medical supervision for at least 2 hours after initial dose, and until blood pressure stabilizes for an additional hour 1

Alternative Dosing from Guidelines:

• The ACC/AHA STEMI guidelines suggest starting ramipril at 2.5 mg twice daily and titrating to 5 mg twice daily as tolerated 3
• For patients with anterior infarction, post-MI LV systolic dysfunction (EF ≤0.40), or heart failure, this regimen is indicated 3

Renal Impairment in Heart Failure:

• Start at 1.25 mg once daily 1
• May increase to 1.25 mg twice daily, up to maximum of 2.5 mg twice daily depending on response and tolerability 1

Critical Monitoring and Safety

Laboratory Monitoring:

• Check baseline renal function, potassium, and blood pressure before initiation 4
• Recheck potassium and creatinine after 5-7 days, then after each dose increase, repeating every 5-7 days until stable 4
• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment 4
• Follow-up at 3 months, then every 6 months thereafter 4

Acceptable Changes:

• Creatinine increase up to 50% above baseline, or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 3
• Small increases in blood urea nitrogen and creatinine are expected and do not require discontinuation 3
• Potassium up to 6.0 mmol/L is acceptable 3

Drug Interactions to Avoid:

• Avoid NSAIDs and COX-2 inhibitors—they worsen renal function and reduce ACE inhibitor efficacy 4
• Avoid potassium-sparing diuretics during initiation unless specifically needed for persistent hypokalemia 4
• Do not combine with potassium supplements or potassium salt substitutes without close monitoring 1

Common Pitfalls and Clinical Pearls

Underdosing:

• Higher doses provide superior outcomes—ramipril 10 mg daily reduced MI, stroke, or CV death by 22% over 5 years in high-risk patients 4
• In heart failure, higher ACE inhibitor doses reduce hospitalizations by 24% compared to low doses 4
• The ATLAS trial demonstrated better outcomes with higher captopril doses (up to 150 mg daily) 3, suggesting the same principle applies to ramipril

Hypotension Management:

• Consider reducing or withholding diuretics for 24 hours before first dose if patient is volume depleted 3
• Appearance of hypotension after initial dose does not preclude subsequent careful titration 1
• If hypotension occurs, reduce concomitant diuretic dose to minimize risk 1

Administration Options:

• Swallow capsules whole, or open and sprinkle contents on 4 oz applesauce, or mix in 4 oz water or apple juice 1
• Mixtures can be prepared and stored up to 24 hours at room temperature or 48 hours refrigerated 1

Target Blood Pressure:

• Aim for <130/80 mmHg in patients with hypertension and stable ischemic heart disease 4
• For CKD patients (stage 3 or higher, or stage 1-2 with albuminuria ≥300 mg/d), target <130/80 mmHg 3

Contraindications:

• Avoid in hypotension, renal failure, and hyperkalemia 3
• Do not use in pregnancy 1